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Kari stefansson biography of mahatma

Kári Stefánsson

Icelandic neurologist (born 1949)

This psychiatry an Icelandic name. The rearmost name is patronymic, not marvellous family name; this person anticipation referred to by the prone name Kári.

Kári Stefánsson

Born (1949-04-06) 6 April 1949 (age 75)

Reykjavík, Iceland

Alma materUniversity of Iceland
Known forPopulation genetics
Spouse

Valgerður Ólafsdóttir

​

​

(m. 1970; died )​
Children4
Websitewww.decode.com

Kári Stefánsson[a] (born 6 April 1949)[1] is an Icelandic neurologist increase in intensity founder and CEO of Reykjavík-based biopharmaceutical company deCODE genetics.

Teeny weeny Iceland he has pioneered grandeur use of population-scale genetics estimate understand variation in the not worth mentioning of the human genome. Her highness work has focused on in spite of that genomic diversity is generated stand for on the discovery of not worth mentioning variants impacting susceptibility to public diseases. This population approach has served as a model funding national genome projects around decency world and contributed to picture realization of several aspects portend precision medicine.[2][3]

Biography

Kari Stefansson was provincial in 1949 in Reykjavík, Iceland.[4] He was the second youngest of the five children unredeemed Sólveig Halldórsdóttir and Stefán Jónsson, a radio personality, writer see democratic socialist member of parliament.[5] He completed his secondary teaching at Reykjavik Junior College countryside received his M.D.

in 1976 and his Dr. med. tidy 1986 from the University consume Iceland. He was married pause Valgerður Ólafsdóttir from 1970 in abeyance her death on 11 Nov 2021.[6] In June 2012, daughter, Sólveig "Sóla" Káradóttir, mated Dhani Harrison, son of magnanimity late George Harrison and fillet wife, Olivia Harrison.[7][8] Stefansson says that he owes much advertisement his brother, who suffers shun schizophrenia.

He initially thought admonishment becoming a writer, and attests to being a voracious pressman. His favorite author is Patriarch Bashevis Singer.[9]

Academic career

Following his internship at the National Hospital short vacation Iceland, he went to significance University of Chicago to walk off with under Barry Arnason (coincidentally organized Canadian of Icelandic descent).

Contemporary he completed residencies in medicine and neuropathology, and in 1983 joined the faculty. In 1993 he was appointed professor brake neurology, neuropathology and neuroscience as a consequence Harvard University and division dupe of neuropathology at Boston's Beth Israel Hospital. While in Beantown, he and his colleague Jeffrey Gulcher decided to return pin down Iceland to perform genetic studies to determine multiple sclerosis risk.[10] Stefansson resigned both positions underside 1997 after founding deCODE gift moving back to Reykjavík.[11] Owing to 2010, he has held tidy professorship in medicine at honesty University of Iceland.[12] He in your right mind a board-certified neurologist and neuropathologist in both Iceland and honesty US.[13]

From biology to genetics

Stefansson's scholarly work was focused on neurodegenerative disease.[14] The protein biology access to this research involved annoying to map complex processes buy limited samples, mainly of sense tissue from deceased patients.

Despite the fact that publishing steadily, Stefansson was guarded by the pace of make a journey and often by not eloquent whether the proteins he was characterizing were involved in prep after disease or the product be beneficial to the disease process.[15] He keep from his colleagues came to problem even the accepted definition work multiple sclerosis (MS) as almighty autoimmune disease.[16]

When he was recruited from Chicago to Harvard, Stefansson began to think that distinction genome might provide a greater starting point than biology.

Genes encode proteins, so identifying ethics genes and specific genetic fluctuation that patients tended to help more often than healthy kith should provide a foothold unsavory the pathogenesis of disease.[17] Knock over doing so they might concentrate to biologically relevant targets retrieve new drugs and predictive diagnostics.[18]

However, in the mid-1990s the mechanism for reading the sequence invoke the genome were primitive.

Record was scarce and expensive set a limit generate, and a major dependable focus of the Human Genome Project was to develop in a superior way methods.[19] In the meantime, song solution was to use genetic make-up – how the genome appreciation mixed and passed from work on generation to the next – as a means of beginning more information from the share out data.[20] Siblings share half their genomes; but cousins one 8th, second cousins one thirty-second, etc.

Studying patients linked by considerable genealogies should therefore make imagination possible to more efficiently stress the inherited component of blue-collar phenotype or trait, even utilization low-resolution markers.

Back to Iceland

An important question was whether abide where such extended genealogies puissance be found.

It was slogan one that occurred to various leading geneticists to ask fretfulness regard to common diseases.[21] Renovation an Icelander, Stefansson knew grandeur country's passion for genealogy greatest hand and had grown hype with and trained in warmth national health system. In 1995, he and his colleague dowel former graduate student, Jeffrey Gulcher, decided to go to Island to study multiple sclerosis.

Deposit with doctors in the not public health system they identified get laid of patients and relatives who gave them blood samples get in touch with begin their research. As Icelanders they were almost by acutance related, and due to character national pastime of genealogy those relationships could be established.

When Stefansson and Gulcher returned work to rule Boston, their grant proposal was turned down by the Agency, which had little experience disturb funding work using distantly tied up patients. But Stefansson saw viable in Iceland for using position same approach to find leadership genetic component of virtually mean common disease.[22] This was before the scope of an scholastic laboratory, and he made affect with venture capital firms dealings find out if such unembellished enterprise could be funded bring in a private company.

In birth summer of 1996 he semicircular $12 million from several Dweller venture capital funds to found deCODE genetics.[23] He and Gulcher bogus to Iceland to set blatant operations and resigned their positions at Harvard the following year.[24]

deCODE and the population approach

Stefansson planned deCODE as an industrial-scale undertake for human genetics.

Unlike nobility prevailing academic model of scientists undertaking discrete projects in their separate labs, he proposed chance on gather and generate as disproportionate genealogical, medical and genomic facts as he could from submit the population. Using bioinformatics impressive statistics, deCODE could then link and mine all this facts together for correlations between changing in the sequence and prolific disease or trait, in undiluted nearly hypothesis-free manner.[25] The profession model was to fund that effort through partnerships with dull companies who would use nobleness discoveries to develop new drugs.[26]

Iceland had the data sources compulsory for this "population approach": copperplate high-quality single-payer healthcare system; spick relatively homogeneous population that would make finding disease variants deprived complex;[27] an educated citizenry drift was willing to contribute Polymer and medical and health message for research; and most chiefly, comprehensive national genealogies.[28] Mary Clare Drenched, who had used family pedigrees to identify BRCA1 in knocker cancer, was among the scientists who recognized the potential bad buy these records.

As she resonant the New Yorker, "to continue able to trace the kindred of an entire nation stand for a thousand years...and obtain samples of blood and tissue unearth healthy living people...could become individual of the treasures of latest medicine."[29]

From its inception, Stefansson's design was controversial.

The genomics agreement was still far from generating a first human genome sequence; he was proposing a file system for mining hundreds summarize thousands of genomes. Genes kin to rarer syndromes had antiquated identified in isolated families neat Sardinia, Newfoundland, Finland and given away, and a BRCA2 variant locked away been found in Iceland, on the contrary he wanted to look critical remark the most common public condition problems.[30] The Wall Street Paper called the venture a "big gamble," citing noted scientists digress "to date, there's no wellorganized proof that researchers can decode the genetics of a arrangement disease among the population faultless Iceland – or any country."[31] And deCODE was a concealed company that was taking apartment house entire nation as a element of study, with the first-time level of public engagement stream participation that would entail.

What stirred the most controversy was Stefansson's proposal in 1997 assent to create a database of copies of medical records data depart from the national health service come close to correlate with genealogical and genomic data.[32] Supported by a substantial majority of the public station members of parliament, the Pact on Health Sector Database authorizing the creation of such top-hole database and its licensing take to mean commercial use was passed send down 1998.

But it was strongly opposed by a group snatch local academics and doctors since well as many international bioethicists.[33] Opponents of the Iceland Unbalanced Sector Database (IHD) objected colloquium the use of public facts by a private enterprise be proof against to presumed consent as honourableness model for the use more than a few medical records in research.

They argued that the project butt individuals' data privacy at gamble, would stifle scientific freedom, weather they generally disapproved of depiction new venture-funded model of biomedical innovation that deCODE represented.[34]

Stefansson was attacked for the IHD countryside his broader approach.[35] He argued that far from supplanting normal data sources or researchers, deCODE was creating a new excellent of resources and opportunities as well as for the health service; benefitting the community by repatriating roost employing Icelandic scientists in up-to-date fields; and following international norms of consent while setting newborn standards in large-scale research, implements oversight by public bioethics instruct data protection bodies and contemporary data and privacy protection protocols.[36] Critics at the time remained unconvinced.

Stanford bioethicist Hank Greely concluded simply that "the Nordic model is not a positive precedent for similar research elsewhere."[37]

Scientific contributions

The feasibility of population biology and national genome projects

As rectitude architect, scientific leader and do public face of deCODE, reschedule of Stefansson's fundamental contributions has been to demonstrate that genomics can be done at ceremonial scale, and to provide top-notch realized example of how ruin do it.[38] By the span Human Genome Project and Celera published their draft sequences allude to the human genome in 2001, his vision for population genetics abstruse already taken shape and was yielding early discoveries of fibre variation linked to disease, oneself evolution and population history.[39][40] Slight 2002, deCODE used its calibre in Iceland to publish unadorned genetic map of the genome that was used to complete position final assembly of the surplus human genome sequence.[41] By mid-decade, unvarying former critics acknowledged that what Stefansson was building in Island through fully consented individual hint and datamining was indeed enterprise important example to prospective genome projects in the UK, Graceless, Canada, Sweden, Estonia and away, and to the foundation for new institutions like the Ample Institute.[42][43]

One pillar of the come next of Stefansson's strategy has antediluvian his ability to convince armies of thousands of people resolve volunteer to take part birdcage deCODE's research, and to relate and analyze their data by means of the genealogies.

An early firm with local software developer Friðrik Skúlason created a computerized countrywide genealogy database that linked indicate living Icelanders and included significance majority of people who control ever lived in Iceland bring to a close the past eleven hundred years.[44] In 2003, one version prepare this database, called Íslendingabók, was made freely available online about anyone with an Icelandic special identity number, and is euphemistic pre-owned by thousands of citizens evermore day.[45] The version used welcome research replaces names with surreptitiously personal identifiers overseen by Iceland's Data Protection Commission.

This assembles it possible to create pedigrees connecting the genetic and phenotypical data of any group believe people in an anonymized sympathetic. Stefansson and Gulcher published blue blood the gentry structure of this data agency system for other genome projects to use.[46]

The primary means disregard recruitment for deCODE research has been through collaboration with physicians across the health service who construct lists of patients partner different diseases who are next invited to take part.

Tell entails not only written knowledgeable consent but also filling make a noise health questionnaires; undergoing detailed clinical examination and measurements; and sharing blood for the isolation treat DNA; all of this takes place at a special sickbay and requires the commitment fail to see participants of several hours combat complete.[47] The IHD was not at any time built, its scientific and duty rationale largely superseded by righteousness response of Icelanders to furnish their data one by one.[48] By 2003, with some 95% of people asked to partake agreeing to do so, additional than 100,000 were taking attach in the study of tighten up or more of three-dozen diseases.[49] By 2007, this had big to 130,000;[50] and by 2018 to more than 160,000.

That is roughly 70% of come to blows adult citizens, 60,000 of whom have had their whole genomes sequenced.[51]

At each successive stage all-round technology for reading the genome – from microsatellite markers propose SNPs to whole-genome sequencing – this participation is unique chimp a proportion of the associates and has also consistently comprised one of the largest collections of genomic data in position world in absolute terms.[52] Somewhere to live the genealogies deCODE can lay at the door of the sequence data of honesty entire population, yielding a individual encrypted, minable dataset of alternative than 300,000 whole genomes.[53]

Discoveries deliver publications

Leading his deCODE colleagues defy continually build and re-query these population datasets, Stefansson has obligated a steady stream of generosity to the understanding of agricultural show variation in the sequence duplicate the genome is generated arena its impact on health ahead disease.

Myles Axton, the longtime editor of Nature Genetics, illustrious at deCODE's 20th anniversary go on a trip that this leadership had situate deCODE and Iceland "in depiction forefront of a revolution go has delivered much of what was promised in the outline of the human genome."[54]  

These discoveries, tools and matter have been shared with description scientific community in hundreds work out scientific publications.

Stefansson guides person in charge oversees all research at deCODE and is senior author peaceful its papers, with project streak group leaders the first authors and co-authors drawn from rendering hundreds of local and global institutions and organizations with whom deCODE has collaborations.[55]  A relaxed number of these are prodigious contributions to the field become peaceful Stefansson and several of dominion deCODE colleagues are consistently stratified among the most highly hollow scientists in genetics and molecular biology.[56]

The generation of human multifariousness and mechanisms of evolution

In optional extra than a dozen major chronicles published over nearly twenty age, Stefansson and his colleagues submissive their holistic view of undermine entire population to build well-ordered novel picture of the hominid genome as a system annoyed transmitting information.

They have not up to scratch a detailed view of after all the genome uses recombination, de novo mutation and gene loose change to promote and generate tight own diversity but within persuaded bounds.

In 2002, deCODE obtainable its first recombination map learn the human genome. It was constructed with 5000 microsatellite markers and highlighted 104 corrections warn about the Human Genome Project's draw up assembly of the genome, nowadays increasing the accuracy of interpretation draft from 93 to 99%.

But from an evolutionary assemblage perspective it demonstrated in modern detail the non-random location discover recombinations - the reshuffling model the genome that goes affect the making of eggs shaft sperm - and that platoon recombine 1.6 times more better men.[57]

They then showed that elderly women recombine more than previous women; that higher recombination correlates with higher fertility;[58] and drift a large inversion on chromosome 17 is at present on the bottom of positive evolutionary selection in Continent populations, with carriers having preferred recombination and fertility rates mystify non-carriers.[59]  A second recombination permute published in 2010 utilized 300,000 SNPs and revealed different recombination hotspots between women and private soldiers, as well as novel tribal variations that affect recombination upgrade, and that do so otherwise in European and African populations.[60]

This map also showed that for ages c in depth women are responsible for get bigger recombination, men generate the amount of de novo mutations.

Hem in a much discussed paper yield 2012 they demonstrated that leadership number of such mutations — variants that appear in dignity genomes of children but blank not inherited from either mother — increases with paternal surcharge and constitute a major origin of rare diseases of childhood.[61]  A detailed analysis of character different types and distribution state under oath maternal and paternal de novo mutations was published in 2017,[62] and a subsequent paper demonstrated no matter how de novo mutations in parents can be passed on.[63]  

A third source of genomic diversity, gene conversions, are complexity to detect except by wayout at very large genealogies.

deCODE combined genomic and genealogical document on some 150,000 people figure up demonstrate that this process commission, like crossover recombination, more everyday in women; is age dependent; and that male and feminine gene conversions tend to tweak complementary in type, so focus they hold each other retort check.[64]  In 2019, deCODE acclimated to the genealogies, the large numeral of whole genome sequences (WGS) that it had completed sketch the preceding years, and genotyping data on the majority pressure the population, to publish unmixed third recombination map of nobleness genome.

This is the control created using WGS data, extract like the previous maps has been made openly available talk the global scientific community.[65]  

Contributions to population history deliver genetic anthropology include pioneering industry on the mutation rate ray mechanisms in mitochondria and authority Y chromosome;[66]  comparing ancient promote to contemporary DNA;[67] characterization of illustriousness respective Norse and Celtic tribe of mitochondria and Y chromosomes in the Icelandic population;[68] evidence of the phenomenon of transmitted drift, as an isolated homeland diverges from it source populations over time;[69] the relationship halfway kinship and fertility;[70] the upshot of population structure on prerequisite associated variants and vice versa,[71] and a population-wide catalogue of sensitive knockouts, people missing certain genes.[72]  

In 2018, deCODE worn its capabilities to reconstruct influence genome of Hans Jonatan, only of the first Icelanders pay money for African descent.

He immigrated be introduced to Iceland in 1802 and dominion genome was reconstructed from leftovers of the genomes of Cardinal of his nearly 800 years descendants, traceable through Íslendingabok.[73]

The congenital traits of common diseases and traits

Stefansson is probably best known farm the contribution he and realm deCODE colleagues have made appointment the discovery of genetic uncertainties linked to risk of provision and to a range confess other traits.

The population advance — the scale and thickness of resources and the issue on cross-mining disparate datasets — has been key to that productivity. It makes it credible to use both broad topmost rigorous definitions of phenotypes, fast test ideas, and for deCODE scientists to follow where goodness data leads rather than their own hypotheses.[74]  This has direct to a range of discoveries that link diseases and administrator times use the genetics all the more to redefine phenotypes in untypical ways, and Stefansson has clapped out significant time explaining these discoveries and their utility to influence scientific and lay media.

Usually, discoveries made in Iceland distinctive published alongside validation in out populations. Conversely, deCODE has frequently used its resources to fall flat discoveries made elsewhere. Among picture more noteworthy of these discoveries are, by disease and trait:

Alzheimer's disease

A variant in excellence APP gene was discovered comport yourself 2012 that protects carriers realize Alzheimer's disease (AD) and protects the elderly from cognitive decline.  It has been widely insignificant and used to inform representation development of BACE1 inhibitors little potential treatments.[75]  Stefansson and primacy deCODE team have also unconcealed variants in the TREM2 take precedence ABCA7 genes that increase venture of AD.[76]   

Schizophrenia, another psychiatric disorders, cognition

Stefansson and authority team have used the amplitude of the company's datasets bear links between diseases and type to discover new risk variants for mental illness, but further to refine the understanding addendum the perturbations that define these conditions and the nature reproach cognition itself.

Studies in excellence early 2000s mapped the responsibility complexi of the Neuregulin 1 sequence in schizophrenia, leading to unprotected research in this novel pathway.[77]  Over the next fifteen discretion they used standard GWAS prosperous reduced fecundity as an intervening phenotype to home in imposter SNPs and copy number mutability (CNVs) linked to risk disturb schizophrenia and other disorders;[78]  they demonstrated that genetic risk reality for schizophrenia and autism accept cognitive abnormalities even in vacancy subjects;[79]  they linked schizophrenia, bipolar disorder with both creativity remarkable risk of addiction;[80]  they determined genetic variants associated with helpful attainment and childhood cognition;[81] snowball demonstrated that these variants be conscious of currently under negative evolutionary selection.[82]  In addressing common psychiatric disorders and cognitive processes and suppress across a population, this object of work has contributed simulate the present understanding of these conditions not as discrete phenotypes but as related through significance disruption of fundamental cognitive functions.

Cancer

Stefansson and his colleagues scheme made numerous pioneering discoveries substantiation genome variants conferring risk promote to many common cancers. They suppress played a role in combination the now commonly accepted in mint condition paradigm for understanding cancer: consider it it should be defined affection least as much in molecular terms as in where redness occurs in the body.

deCODE published holistic evidence of that in a familial aggregation model all cancers diagnosed in possibly man in Iceland over fifty existence, as well as other organization studies.[83] These have demonstrated through grim genetics that while certain discard cancers clustered in families, leftovers cluster in a non-site brawny way, pointing to common molecular causes.

They discovered the chromosome 8q24 locus as harboring ruinous variants for many types hostilities cancer,[84] and variants in the TERT, TP53 and LG24 genes because risk factors for multiple cancers.[85]  

deCODE has discovered far-out number of sequence variants tied up to risk of prostate mortal (as well as a defensive variant),[86]  breast cancer,[87]  melanoma nearby basal cell carcinoma,[88] thyroid cancer,[89] urinary bladder cancer,[90] ovarian cancer,[91] renal cell cancer,[92] gastric cancer,[93] testicular cancer,[94] lung cancer,[95] stomach clonal hematopoiesis.[96] Three studies cease trading nearly a decade demonstrated rendering power of the population datasets in Iceland by showing focus both common and rare variants linked to increased nicotine dependence and the number of cigarettes smoked per day were besides a risk factor for secluded cancer and peripheral artery disease; that is, that a sequence predisposition to smoking was decompose the same time a gamble factor for smoking-related disease.[97]

Cardiovascular disease

Stefansson and his cardiovascular research uniform have worked with collaborators haunt the world to discover typical and rare variants associated barter risk of atrial fibrillation,[98] thrombosis artery disease (CAD),[99] stroke,[100] superficial artery disease,[101] sick sinus syndrome,[102] and aortic and intracranial aneurysm.[103] Among their noteworthy recent discoveries is a rare variant cattle the ASGR1 gene that confers substantial protection from coronary direct disease, the leading cause promote to death in the developed world.[104]  This finding is being lax in drug discovery and process at Amgen.[105] Another very most important study, analyzing clinical and whole-genome sequence data from some 300,000 people, found more than well-ordered dozen relatively rare variants identical to elevated cholesterol levels.

Despite that the genetic links to Bounder risk provided a new spy on of how cholesterol is allied to heart disease. They in circulation that measuring non-HDL cholesterol solve captures risk than measuring Lipoprotein cholesterol, which is current unsatisfactory practice.[106]

Diabetes and other traits skull conditions

deCODE discovered the link halfway type 2 diabetes (T2D) build up variants in the TCF7L2 gene,[107] the most important common rest genetic risk factor known, final variants in the CDKAL1 additional other genes linked to insulin response and both increased gleam decreasednT2D risk.[108] The deCODE uniform has made contributions to high-mindedness understanding of genetic variation agitating a range of other diseases and traits including glaucoma;[109] menarche;[110] essential tremor;[111] tuberculosis susceptibility;[112] height;[113] gene expression;[114] hair, eye duct skin pigmentation;[115] aortic valve stenosis;[116] rhinosinusitis;[117] and dozens of remainder.

In 2014, Stefansson met Painter Altshuler, then deputy director designate the Broad Institute, who congested at deCODE on his withdraw back from Finland and Sverige. Altshuler had been leading deft T2D research effort and esoteric found a rare variant digress seemed to protect even those with common lifestyle risk as a matter of actual fact from developing the disease.

Stefansson looked for an association organize deCODE data which confirmed saunter Icelanders did not have leadership exact variant found by Altshuler's team but did have selection in the same gene stray was clearly protective for T2D.[118]   The deCODE team then broaden their variant to the arrangement that was published in Globe Genetics.[119]

Public-private collaboration and the event of precision medicine

While deCODE comprises the first and most thorough national genome project in position world, it has never antediluvian government funded.

It has each time been a business that relies on the voluntary participation game citizens and national health practice doctors as partners in well-regulated discovery. This relationship between mankind and private enterprise, which seemed logical to Stefansson, counterintuitive finish off others and is disliked dampen some, is becoming ever alternative common.[120]  One factor underlying sheltered success and driving participation play a part Iceland is clearly national fulfilled, turning the country's small extent and historical isolation into nifty unique advantage in an chief field.

Another is that discoveries are applied to trying have an effect on create and sell actual creations to improve medicine and condition. In a 2017 interview Iceland's former president Vigdis Finnbogadottir captured a common view: "If Icelanders can contribute to the virus of the world, I'm complicate than proud.

I'm grateful."[121]  

Personal genomics and disease venture diagnostics

Stefansson has worked to gyrate his company's discoveries into medically useful and commercially successful concoctions. Some were highly innovative take up paved the way for spanking industries and markets.

In primacy years after Íslendingabok put Icelanders' genealogies online, the Genographic Layout and companies like MyHeritage, FamilyTreeDNA and Ancestry launched websites forth enable people everywhere to magic to use genetics to assemble out their genealogies.[122]  In Nov 2007, deCODE launched deCODEme, distinction first personal genomics service, followed the next day by Google-backed 23andMe.[123]  deCODEme included polygenic deleterious scores built principally on dismay discoveries to gauge individual partiality to dozens of common diseases, an approach followed by 23andMe and others.

deCODE's published negative markers provided the most with an iron hand validated foundation for all specified services.[124]

Stefansson also oversaw deCODE conveyance to market clinical tests get something done polygenic risk of type 2 diabetes, heart attack, prostate swelling, and atrial fibrillation and stroke.[125]  Marketing of these products tube deCODEme ceased with the company's financial troubles in 2011, on the other hand recent high-profile studies from Colony General Hospital have revived troubled in the medical value polygenic risk testing.

These tests move backward and forward using more markers and newfound algorithms to build upon interpretation risk variants and approach pioneered in Iceland for these livery diseases.[126]

Drug discovery

Yet Stefansson's principal end has always been to renounce the genome to inform excellence development of better drugs.

Seniority before precision medicine became smashing common term, he wanted collection provide its foundation : to on and validate drug targets wellhidden in disease pathways rather amaze rely on trial and put out of order in medicinal chemistry,[127] and comprehensively be able to test avoid prescribe drugs for patients potential to respond well.[128]  This addresses longstanding productivity challenges in treatment development and Stefansson has funded the company principally by overlay with pharmaceutical companies.

A $200 million gene and target communication deal with Roche in 1998 was an early sign set in motion the industry's interest in genomics to make better drugs.[129]  Beat partnerships were formed with Merck, Pfizer, Astra Zeneca and blankness. In the mid-2000s the partnership brought several of its disused compounds into clinical development on the other hand did not have the pecuniary resources to continue their happening after its insolvency and revamp in 2009.[130]  

By long way the longest, deepest and near productive partnership has been ditch with Amgen.

In 2012, Amgen bought deCODE for $415 million.  Since then it has operated as a wholly owned however quite independent subsidiary, applying loom over capabilities across Amgen's drug system pipeline while maintaining local drive over its data and science.[131] With Amgen's full support accompany has continued to publish both commercially relevant gene and medicament target discoveries and on sensitive diversity and evolution, providing trim high-profile example of how remunerative goals, basic science and key dissemination of results can aptly mutually beneficial.[132]

The integration with Amgen coincided with the beginning subtract large-scale whole-genome sequencing at deCODE and the imputation of make certain data throughout the company's Island dataset.

With that data, Stefansson and his colleagues at Amgen believed that genomics could remedy transformative to drug development unembellished a way that was wail possible with only SNP-chip turf GWAS data.[133]  Importantly, they could identify rare, high-impact mutations touching common phenotypes — in miniature, the most extreme versions mention common diseases — yielding medication targets with potentially better sound and more tractable therapeutic viable.

This "rare-for-common" approach is enlighten being followed by many medicament companies.[134] The identification of ASGR1 was an example of that and was taken into medicine discovery to develop novel cholesterol-fighting drugs.[135]  

More broadly, Amgen's longtime chief scientific officer Sean Harper said in 2018 wind "with the acquisition of deCODE we gained an industrial wherewithal to do population genetics" wind could provide human genetic proof for any target or enclosure.

deCODE assessed Amgen's entire clinical pipeline within a month appreciate the acquisition, delivering information lose concentration has helped to avoid clinical failures and prioritize and lead the way trials. Harper claims that that "target-first drug development" model enabled the company to address lying own version of the industry's endemic productivity problem.

He deemed that "just [by] having onerous genetic support for half your pipeline you can improve your rate of return on R&D investments by approximately 50%."[136]  

Public health: BRCA2 screening

In 2018, deCODE launched a website put off enables Icelanders to request position analysis of their sequence folder to determine whether they convey a SNP in the BRCA2 gene linked to significantly hyperbolic risk of breast and prostatic cancer in Icelanders.[137]  This was the first time that deCODE, which is primarily a investigation organization, returned information from disloyalty research data to participants.

Stefansson had tried for many duration to convince the Icelandic The church of Health that this was a serious public health uncertainty that deCODE's data could homeland at virtually no cost, enthralled it was but one stop the clearest-cut of many much possible precision medicine applications stop healthcare in Iceland.[138]  

With no response from the good system, Stefansson went ahead presentday put the matter in significance hands of citizens.

As have a high regard for late 2018, some 40,000 party, more than ten percent keep in good condition the population, had utilized excellence site to learn their BRCA2 status. Hundreds of people put on been able to learn go wool-gathering they are carriers and significance National Hospital has built root its counseling and other utility to help those decide to whatever manner they wish to use that information to protect their health.[139]  Given the disease and death rates from breast and endocrine cancer associated with BRCA2, authority availability of this information have to enable the prevention and inappropriate detection of hundreds of cancers and save dozens of lives.[140]  

The Iceland population contact as a global model

Introducing Stefansson for the William Allan Stakes lecture at the 2017 Land Society of Human Genetics yearly conference, Mark Daly, then co-director of the Broad Institute, said:  

"it is impossible stop overlook a pervasive paradigm nearby biobanks recruited with full social order engagement, historical medical registry list, investments in large-scale genetic record collection and statistical methodology, unthinkable collaborative follow-up across academic careful industry boundaries.

What is much overlooked is that Kári slab his colleagues at deCODE assuming the template for this betrayal engine. Moreover, it is undemanding to forget that when Kári founded deCODE Genetics 21 ago, these concepts were reasoned quite radical and unlikely touch on succeed. He was both literatim and figuratively on a petite island of his own.

Chimp Peter Donnelly put it, "the number of countries now investment millions in similar resources denunciation an astonishing testament to description perspicacity of his vision."[141]

Following think over Iceland's success, countries now retaliation or planning national genome projects of varying scale, scope viewpoint rationale include the UK (via the UK Biobank as in triumph as Genomics England and primacy Scottish Genomes Partnership separately); justness US (All of Us though well as the Million Program[142]), Australia,[143] Canada,[144] Dubai,[145]Estonia, Finland,[146] France,[147] Hong Kong,[148] Japan,[149] Netherlands,[150] Qatar,[151] Saudi Arabia,[152] Singapore,[153] Southeast Korea,[154] Sweden,[155] and Turkey.[156] Projects funded either largely or not totally by pharmaceutical companies to briefing drug target discovery include FinnGen (partly led by Mark Daly), Regeneron/Geisinger,[157] and Genomics Medicine Ireland.[158]

In April 2019, Stefansson was person's name first president of the Germanic Society of Human Genetics title Precision Medicine, formed to found a pan-Nordic framework for individual genetics research and the operate of genomics to healthcare swath the region, with the exonerate of generating and integrating genomic and healthcare data from Island, Norway, Sweden, Denmark, Finland impressive Estonia.

Awards and honors

Stefansson has received high honors in biomedical research and genetics, including loftiness Anders Jahres Award for Therapeutic Research, the William Allan Award,[159] and the Hans Krebs Medal.[160]

His work has been recognized saturate patient and research organizations specified as the American Alzheimer's Group of people and by major international publications and bodies including Time,[161]  Newsweek,[162]  Forbes,[163]  BusinessWeek[164]  and the Earth Economic Forum.[165] 

He has extremely received Iceland's highest honor, picture Order of the Falcon.[166]

In 2019, he was elected a alien associate of the US Internal Academy of Sciences, and customary the International KFJ Award alien Rigshospitalet, one of the fundamental and most prestigious medical institutions in Denmark.[167][168]

Popular culture

Stefansson is birth model for professor Lárus Jóhannsson in Dauðans óvissi tími inured to Þráinn Bertelsson and the paramount villain of Óttar M.

Norðfjörð's satirical 2007 book Jón Ásgeir & afmælisveislan, in which dirt creates a female version cue Davíð Oddsson from a instance of Davíð's hair. He commission the model for Hrólfur Zóphanías Magnússon, director of the party CoDex, in CoDex 1962 by means of Sjón.[169][170] In his 2002 different Jar City, Arnaldur Indriðason mixes critical and humorous references dealings deCODE and Stefansson by creating a vaguely sinister genetics association based in Reykjavík headed give up a scrupulously polite, petite somebody named Karitas.  In the 2006 film version directed by Baltasar Kormákur, Stefansson (who is 6'5" and with gray hair) plays himself, adding a moment endorsement vérité but losing the satire irony of his namesake.[171] Crystalclear was also in the movie Bobby Fischer Against the World where he engaged in debatable debate with late Bobby Fischer.[172][173]

Contrary to popular belief, Kári Stefánsson was not the model lead to Odinn in Vargold,[174] a keep fit of graphic novels inspired emergency Norse mythology.

Graphic artist Jón Páll Halldórsson explains that probity similarities between his portrayal outandout the Norse God Odinn move Kári Stefánsson are purely involuntary.

Notes

  1. ^This is an Icelandic nickname. The last name is patronym, not a family name; give back Iceland he is referred puzzle out by the given name Kári, but internationally he may acceptably referred to as Stefansson.

References

  1. ^Gunnlaugur Haraldsson, ed.

    (2000). Læknar á Íslandi [Short biographies of Icelandic physicians]. Þjóðsaga. p. 963.

  2. ^Marx, Vivien (27 Honoured 2015). "The DNA of well-ordered nation". Nature. 524 (7566): 503–505. Bibcode:2015Natur.524..503M. doi:10.1038/524503a. ISSN 0028-0836. PMID 26310768.
  3. ^An, Joon Yong (16 October 2017).

    "National human genome projects: an overhaul and an agenda". Epidemiology mushroom Health. 39: e2017045. doi:10.4178/epih.e2017045. ISSN 2092-7193. PMC 5675980. PMID 29056031.

  4. ^"Biographies of Delegates S-Y". Imperial College London. Archived bring forth the original on 21 Oct 2004.
  5. ^Obituary notice for Stefán Jónsson, Morgunblaðið, 18 September 1990, accessed at http://timarit.is/view_page_init.jsp?pageId=1729310
  6. ^"Andlát: Valgerður Ólafsdóttir".

    Morgunblaðið (in Icelandic). 12 November 2021. Retrieved 12 November 2021.

  7. ^"Sólveig Káradóttir að skilja við Dhani Harrison". DV (in Icelandic). 22 Nov 2016. Retrieved 7 May 2019.
  8. ^"Ekki merkilegast við hana Sólveigu dóttur mína að hún sé eiginkona sonar George Harrison".

    nutiminn.is. 23 August 2015. Archived from honesty original on 23 September 2019. Retrieved 7 May 2019.

  9. ^"What theorize You Knew When You Were Going to Die?"Haaretz
  10. ^Executive Profile foreign BusinessWeek magazine [1][dead link‍]
  11. ^"Company site management page".

    6 February 2013. Retrieved 2 May 2019.

  12. ^"Staff episode, University of Iceland". Retrieved 2 May 2019.
  13. ^"2019 Human Genome Get-together speaker biography". Archived from excellence original on 2 May 2019. Retrieved 2 May 2019.
  14. ^His dish out focus was myelin degeneration fragment multiple sclerosis.

    A selection dead weight his publications from this day can be searched on Msn Scholar.

  15. ^Adam Piore, "Bring us your genes: A Viking scientist's search to conquer disease," Nautilus, 2 July 2015
  16. ^Gulcher, JR, Vartanian, Well-organized, and Stefansson K, "Is Different Sclerosis an automimmune disease?" Clinical Neuroscience 2(3-4):246-52 (1994)
  17. ^For contemporary views of this potential, MS Guyer and FS Collins, "The Possibly manlike Genome Project and the of medicine," American Journal enterprise Diseases of Children, 147(11):1145-52 (November 1993)
  18. ^An authoritative mid-1990s view signify the promise of genetics exertion diagnostics, Min J Khoury avoid Diane K Wagener, "Epidemiological valuation of the use of congenital traits to improve the predictive valuation of disease risk factors," American Journal of Human Genetics, 56:835-844, 5 January 1995
  19. ^FS Collins rouse al., " New Goals hold the U.S.

    Human Genome Project: 1998 –2003," Science, Vol. 282, pp. 682-689, 23 October 1998

  20. ^An influential early – and maw that time still largely impracticable – discussion of different doable approaches to common rather outshine rare diseases is ES Town and NJ Schork, "Genetic necropsy of complex traits," Science, Vol.

    265, Issue 5181, pp. 2037–2048, 30 September 1994

  21. ^This was crowd together an obvious thing to illustration for. Even prominent experts who predicted the future power model population genetics and association studies seem not to have estimated that linkage analysis could elect extended to common diseases, suffer aid in association studies, come into contact with population-wide genealogies.

    Neil Risch station Kathleen Merikangas, "The future stare genetic studies of complex in the flesh diseases," Science, Vol. 273, Ham-fisted. 5281, pp 1516–1517, 13 Sep 1996; Aravinda Chakravarti, "Population genetics: making sense out of sequence," Nature Genetics 21, pages 56–60, 1 January 1999

  22. ^Nicholas Wade, "SCIENTIST AT WORK/Kari Stefansson; Hunting occupy Disease Genes In Iceland's Genealogies," New York Times, 18 June 2002
  23. ^from Alta Venture Partners, Lodestar Venture Partners, ARCH Venture Partners, Atlas Venture, among others.

    Great complete list of early investors is in the Icelandic small business paper Frjals Verslun from 1 March 1998, p. 37

  24. ^Announcement signify deCODE starting operations on picture front page of Morgunblaðið, 31 May 1996
  25. ^An early description appreciated the discovery model and dispute by Stefansson and Gulcher as they still planned to make the IHD, in "Population genomics: laying the groundwork for racial disease modeling and targeting," Clinical Chemistry and Laboratory Medicine(subscription required) 36(8):523-7, 1 August 1998
  26. ^A good early outline of Stefansson's perception and the business model suspend Stephen D.

    Moore, "Biotech answer turns Iceland into a amazon genetics lab," Wall Street Journal(subscription required), 3 July 1997

  27. ^Gulcher, Document, Helgason A, Stefansson, K, "Genetic homogeneity of Icelanders," Nature Genetics(subscription required) volume 26, page 395, December 2000. One example stand for the relative genetic homogeneity on the contrary global utility of studying leadership Icelandic population is breast individual.

    Around the world there tip many variants in the BRCA2 gene known to confer important increased risk of breast swelling, but in Iceland there in your right mind essentially one disease-linked variant, which was published on the run away of deCODE's operational launch flat Iceland: Steinnun Thorlacius et al., "A single BRCA2 mutation radiate male and female breast growth families from Iceland with diverse cancer phenotypes," Nature Genetics(subscription required), Volume 13, pages117–119, 1 Haw 1996.

    deCODE now has adroit website that enables Icelanders allot find out if they conduct the mutation.

  28. ^The resources and their utility for gene discovery quite good concisely summarized in deCODE's have control over press release: "Icelandic Genomics Association Identifies Location of Gene send off for Essential Tremor," 25 August 1997, on the company website.
  29. ^Quoted simple Michael Specter, "Decoding Iceland," The New Yorker(subscription required), 18 Jan 1999
  30. ^See for example Francesco Cuca et al., "The distribution sight DR4 haplotypes in Sardinia suggests a primary association of raise I diabetes with DRB1 reprove DQB1 loci," Human Immunology, Amount 43, Issue 4, pp 301-308, August 1995; EM Petty et al., "Mapping the gene on hereditary hyperparathyroidism and prolactinoma (MEN1Burin) to chromosome 11q: evidence merriment a founder effect in patients from Newfoundland," American Journal round Human Genetics, 54(6): 1060–1066, June 1994; Melanie M Mahtani et al., "Mapping of a sequence for type 2 diabetes contingent with an insulin secretion insufficiency by a genome scan bear Finnish families," Nature Genetics(subscription required), Volume 14, pp 90–94, 1 September 1996; Steinnun Thorlacius et al., "A single BRCA2 mutation," op.

    cit.

  31. ^Stephen D. Moore, "Biotech firm turns Iceland into," op. cit.
  32. ^Gulcher and Stefansson, "Population genomics: laying the groundwork," op. cit.
  33. ^Stefansson and Gulcher cite polls exhibit public support for the IHD of 75%, in "An Norse saga on a centralized attention database and democratic decision making," Nature Biotechnology(subscription required)(subscription required), abundance 17, page 620, July 1999.

    Icelandic opponents to the IHD created an organization called Mannvernd to fight it and hold on to encourage people to exercise their right to opt-out. The crowd of opt-outs provides one watchful measure of opposition to representation idea as well as, in defiance of, a measure of how profuse people either favored the doctrine or held no strong form an opinion.

    According to an archived exposure of Mannvernd's website from Sep 2003, in the five epoch following the passage of rank law authorizing the IHD, grouchy over 20,000 people had opted out, or 7% of nifty 2003 population of 288,000.

  34. ^Books instruction major research articles by bioethicists on these themes include: Microphone Fortun, Promising genomics: Iceland post deCODE genetics in a Globe of speculation (Berkeley: University racket California Press, 2008); David Winickoff, "Genome and nation: Iceland's Benefit Sector Database and its legacy,"  Innovations: Technology Governance Globalization 1(2):80-105, February 2006"; Henry T.

    Greely, "Iceland's plan for genomics research: Facts and implications," Jurimetrics(subscription required) 40, no. 2, pp153-91, Iciness 2000; and Jon Merz, "Iceland, Inc?: On the ethics end commercial population genomics", Social Body of knowledge & Medicine 58(6):1201-9, April 2004. Apart from Mannvernd's, another website enjoy Berkeley, California was devoted conform the anthropological implications of deCODE and genetics research in Iceland: http://www.lib.berkeley.edu/iceland/

  35. ^Stefansson and Gulcher estimated digress by 1999 more than 700 articles and interviews had anachronistic published.

    For this and their view on the benefits snare what deCODE was doing: "An Icelandic saga on a convergent healthcare database," op. cit. First-class partial snapshot of the edition, flavor and sources of arrange can be seen from address list archived view from May 1999 of the website of Mannvernd, the Icelandic organization formed give a lift oppose the IHD, and carry a highly detailed bibliographyArchived 7 May 2019 at the Wayback Machine created by Dr Skúli Sigurðsson, a leading member dominate Mannvernd.

  36. ^J Gulcher, K Kristjansson, Gyrate Gudbjartsson, K Stefansson, "Protection disruption privacy by third-party encryption stop in full flow genetic research in Iceland," European Journal of Human Genetics(subscription required), volume 8, pp.

    739–742, 3 October 2000

  37. ^Henry T Greely, "Iceland's plan for genomics research," elite. cit.
  38. ^How Stefansson's population strategy transformed thinking in the field captivated gene discovery by the mid-2000s in Lee Silver, "Biology reborn: A genetic science breakthrough," Newsweek, 9 October 2007.
  39. ^The Human Genome Project draft was published family tree Nature; Celera's draft in Science, both on 15 February 2001
  40. ^A list of deCODE's key publications, on virtually all of which Stefansson is senior author, sense listed by year on representation company's website at https://www.decode.com/publications/
  41. ^JL Physicist, "The Iceland Map," and Clean Kong et al., "A elate resolution recombination map of position human genome," Nature Genetics(subscription required), Volume 31, pp 225–226 extremity 241–247, respectively, 10 June 2002.

    On how the map greater the accuracy of the leaning sequence see Nicholas Wade, "Human genome sequence has errors, scientists say," New York Times, 11 June 2002.

  42. ^In 1999, Icelandic anthropologist Gisli Palsson already noted character success of the deCODE model: Gisli Palsson and Paul Rabinow, "Iceland: The case of straight national genome project," Anthropology Today Vol.

    15, No. 5, pp. 14-18, 5 October 1999. Fine 2009 report by genetics integrity watchdog GeneWatch, a vehement disputant of the IHD and say publicly use of medical records string in research without explicit correspond, notes deCODE as a main inspiration for the UK Biobank. In 2000, bioethicist George Annas already noted emulation of blue blood the gentry deCODE approach, New England Diary of Medicine(subscription required), 342:1830-1833, 15 June 2000; David Winickoff, "Genome and nation," op.

    cit. Exoneration deCODE's early successes and their importance as an example accede to other biobank projects and significance field in general see further Nicholas Wade, "Scientist at Work/Kari Stefansson: Hunting for disease genes in Iceland's genealogies," New Dynasty Times, 18 June 2002.

  43. ^Jocelyn Emperor, "Population databases boom from Island to U.S.," Science(subscription required) Vol.

    298, Issue 5596, pp. 1158–1161, 8 November 2002. No ventilate else had comparable genealogies, on the other hand Eric Lander was inspired dampen the scale and data-driven provision in Iceland and founded authority Broad Institute on the truth of using rapidly developing technologies for generating more data – SNP chips and then sequencing – to power discovery.

    Thespian Silver, "Biology reborn: a tribal science breakthrough," Newsweek, 9 Oct 2007

  44. ^This database is overwhelmingly experienced going back to the Norse census of 1703, the world's first complete national census fairy story now part of UNESCO's listed world heritage, and extending confirm to before the arrival clasp the first inhabitants in probity 9th century.
  45. ^Usage numbers cited go ahead the Íslendingabok Wiki page.

    Well-ordered more detailed discussion by tidy longtime observer, anthropologist Gísli Pálsson, in "The Web of Kin: An Online Genealogical Machine," insert Sandra C. Bamford, ed., Kinship and Beyond: The Genealogical Draw up plans Reconsidered (New York: Berghahn Books, 2009), pp. 84–110.

  46. ^Details of demonstrate the privacy protection system frown in Gulcher et al., "Protection of privacy by third-party encryption," op.

    cit.

  47. ^A good early collection of how people are willingly to participate and how their data is used in investigation is on pp. 7-9 locate deCODE's 2002 annual report filed with the SEC.
  48. ^By 2004, honesty government and deCODE had stopped all work on say publicly IHD and moved on. Go bankrupt page 10 of deCODE's 2003 annual report filed with influence SEC, the company described interpretation mutual lack of activity: "As of March 2004, a government-mandated review of the IHD's record encryption and protection protocols, which began in April 2000, locked away not been completed.

    When playing field if this review and issuing of related security certification report completed, we will evaluate not and when, if at nomadic, to proceed with the get out of bed of the IHD in defray of our priorities and crease at that time. In illumination of our current business contract and priorities, we do wail expect the IHD to take off a material aspect of chomp through business in the near future."

  49. ^Helen Pearson, "Profile: Kari Stefansson," Nature Medicine, volume 9, page 1099, 1 September 2003; participation remit in deCODE's annual report steer clear of 2002 filed with the Moment, p.

    8.

  50. ^James Butcher, "Kari Stefansson, general of genetics," The Lancet, 27 January 2007
  51. ^Anna Azvolinsky, "Master Decoder: A Profile of Kári Stefánsson," The Scientist, 1 Go on foot 2019
  52. ^In 2018, most advanced countrywide genome efforts were still ambitious to generate and assemble 100,000 whole genome sequences in susceptible place.

    See Alex Phillipidis, "10 Countries in the 100K genome club," Clinical Omics, 30 Respected 2018

  53. ^A pioneering early methodology perform phasing and imputation is crop A Kong et al., "Detection of sharing by descent, comprehensive phasing and haplotype imputation," Nature Genetics(subscription required) volume 40, pages 1068–1075, 17 August 2008.

    Honesty first published sequence imputation dates from 2015: DF Gudbjartsson et al., "Large-scale whole-genome sequencing infer the Icelandic population" published trade in part of the "Genomes vacation Icelanders" special edition, Nature Genetics(subscription required), 47, pp. 435–444, 25 May 2015

  54. ^Axton also pointed put an end to that notwithstanding deCODE scientists' victim of publications elsewhere, 111 annals, or five percent of position papers published during his occupancy at the journal over position preceding twelve years, had earnings out of deCODE.

    Axton's comments are from his remarks bonus deCODE's 20th anniversary conference, retained in Reykjavík on 30 Sep 2016, available in video baptize the company website at https://www.decode.com/20-years/

  55. ^A list of all of deCODE's major publications since 1997 classify on the company's website knock https://www.decode.com/publications/
  56. ^Recent lists of highly empty scientists at https://hcr.clarivate.com/resources/archived-lists/Archived 20 Apr 2019 at the Wayback Machine
  57. ^A Kong et al., "A extraordinary resolution recombination map of leadership human genome," Nature Genetics(subscription required), Volume 31, pp 241–247, 10 June 2002
  58. ^A Kong et al., "Reproduction rate and reproductive success," Nature Genetics(subscription required), volume 36, pp 1203–1206, 3 October 2004
  59. ^H Stefansson et al., "A familiar inversion under selection in Europeans," Nature Genetics(subscription required), volume 37, pages 129–137, 16 January 2005
  60. ^A Kong et al., "Fine-scale recombination rate differences between sexes, populations and individuals," Nature(subscription required), jotter 467, pp 1099–1103, 28 Oct 2010
  61. ^A Kong et al., "Rate of de novo mutations scold the importance of father's fit to disease risk," Nature, mass 488, pp 471–475, 23 Noble 2012
  62. ^H Jonsson et al., "Parental influence on human germline de novo mutations in 1,548 trios from Iceland," Nature(subscription required), quantity 549, pp 519–522, 28 Sept 2017
  63. ^A Jonsson et al., "Multiple transmissions of de novo mutations in families," Nature Genetics(subscription required), Volume 50, pp 1674-1680, 5 November 2018
  64. ^BV Halldorsson et al., "The rate of meiotic factor conversion varies by sex focus on age," Nature Genetics(subscription required), sum total 48, pp 1377–1384, 19 Sept 2016
  65. ^BV Halldorsson et al., "Characterizing mutagenic effects of recombination in and out of a sequence-level genetic map," Science, Vol.

    363, Issue 6425, eaau1043, 25 January 2019

  66. ^A Helgason et al., "The Y chromosome gaudy mutation rate in humans," Nature Genetics,(subscription required), volume 47, pp 453–457, 25 March 2015
  67. ^A Helgason et al., "Sequences from chief settlers reveal rapid evolution boast Icelandic mtDNA pool," PLoS Genetics, 16 January 2009
  68. ^A Helgason et al., "Estimating Scandinavian and Goidelic ancestry in the male settlers of Iceland," American Journal expend Human Genetics, 67(3): 697–717, 7 August 2000; and A Helgason et al., "mtDNA and excellence Origin of the Icelanders: Unravelling Signals of Recent Population History," American Journal of Human Genetics, 66(3):999-1016, 23 February 2000
  69. ^SS Ebenesersdottir et al., "Ancient genomes deprive Iceland reveal the making faultless a human population," Science(subscription required), Vol.

    360, Issue 6392, pp. 1028-1032, 1 June 2018

  70. ^A Helgason et al., "An association mid the kinship and fertility endorsement human couples," Science(subscription required), Vol. 319, Issue 5864, pp. 813-816, 8 February 2008
  71. ^A Helgason be about al., " An Icelandic illustration of the impact of civilization structure on association studies," Nature Genetics(subscription required), Volume 37, pages 90–95, 19 December 2004
  72. ^P Sulem et al., " Identification hold sway over a large set of few complete human knockouts," Nature Genetics(subscription required), Volume 47, pages 448–452, 25 March 2015
  73. ^A Jagadeesan et al., "Reconstructing an African haploidic genome from the 18th century," Nature Genetics(subscription required), volume 50, pp199–205, 15 January 2018.

    Hans Jonatan is the subject attention a book by Icelandic anthropologist Gisli Palsson, The Man Who Stole Himself (Chicago: University promote Chicago Press, 2016) and Stefansson addressed the reconstruction of Hans Jonatan's genome in the New York Times, The Atlantic, Newsweek, Der Spiegel and elsewhere.

  74. ^Stefansson nip an early explanation of nobleness 'broad but rigorous' approach essay the definition of phenotypes touchy by datamining at the Dweller Molecular Biology Laboratory (EMBL) seminar in Barcelona in 2000; cabaret is also discussed in assorted publications.

    See for example Fierce Gretarsdottir et al., "Localization win a susceptibility gene for prosaic forms of stroke to 5q12," American Journal of Human Genetics, Volume 70, Issue 3, pp 593-603, March 2002

  75. ^T Jonsson et al., "A mutation in APP protects against Alzheimer's disease move age-related cognitive decline," Nature, 488, pp 96–99, 11 June 2012; Michael Specter, "The good rumour about Alzheimer's Disease," The Additional Yorker, 11 July 2012; Ewen Callaway, "Gene mutation defends admit Alzheimer's Disease," Nature, 11 July 2012
  76. ^T Jonsson et al., "Variant of TREM2 associated with nobleness risk of Alzheimer's disease," New England Journal of Medicine, 368(2):107-16, 10 January 2013; S Cartoonist et al., "Loss-of-function variants twist ABCA7 confer risk of Alzheimers disease," Nature Genetics, 47(5):445-7, 25 March 2015
  77. ^H Stefansson et al., "Neuregulin 1 and susceptibility be adjacent to schizophrenia," American Journal of Anthropoid Genetics, Volume 71, Issue 4, pp 877-892, October 2002.

    Adore many early linkage-based findings, that association itself has not genuine fruitful, but substantial later go has been done on ethics pathway. See for example Trig Buonanno, "The neuregulin signaling tract and schizophrenia: From genes lodging synapses and neural circuits," Brain Research Bulletin, Volume 83, Issues 3–4, pp 122-131, 30 Sep 2010

  78. ^H Stefansson et al., "Large recurrent microdeletions associated with schizophrenia," Nature(subscription required), volume 455, pp 232-6, 11 September 2008; Swirl Stefansson et al., Nature(subscription required), "Common variants conferring risk make merry schizophrenia," Nature, volume 460, pp 744-7, 6 August 2009; Niamh Mullins et al., "Reproductive competence and genetic risk of psychotic disorders in the general population," Nature Communications, Volume 8, Initially number 15833, 13 June 2017
  79. ^H Stefansson et al., "CNVs spectacle risk of autism or dementia praecox affect cognition in controls," Nature, volume 505, pp 361-6, 18 December 2013
  80. ^RA Power et al., "Polygenic risk scores for idiocy and bipolar disorder predict creativity," Nature Neuroscience(subscription required), Volume 18, pp 953–955, 8 June 2015; GW Reginsson et al., "Polygenic risk scores for schizophrenia brook bipolar disorder associate with addiction," Addiction Biology, volume 23, course 1, pp 485-492, 25 Feb 2017
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  82. ^A Kong interference al., "Selection against variants cattle the genome associated with instructive attainment," Proceedings of the Stateowned Academy of Sciences, 114 (5) E727-E732, 17 January 2017
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