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dc.contributor.author
Lowe, Jennifer K.
dc.contributor.author
Maller, Julian B.
dc.contributor.author
Pe'er, Itsik
dc.contributor.author
Neale, Benjamin M.
dc.contributor.author
Salit, Jacqueline
dc.contributor.author
Kenny, Eimear E.
dc.contributor.author
Shea, Jessica L.
dc.contributor.author
Burkhardt, Ralph
dc.contributor.author
Smith, J. Gustav
dc.contributor.author
Ji, Weizhen
dc.contributor.author
Noel, Martha
dc.contributor.author
Foo, Jia Nee
dc.contributor.author
Blundell, Maude L.
dc.contributor.author
Skilling, Vita
dc.contributor.author
Garcia, Laura
dc.contributor.author
Sullivan, Marcia L.
dc.contributor.author
Lee, Heather E.
dc.contributor.author
Labek, Anna
dc.contributor.author
Ferdowsian, Hope
dc.contributor.author
Auerbach, Steven B.
dc.contributor.author
Lifton, Richard
dc.contributor.author
Newton-Cheh, Christopher
dc.contributor.author
Breslow, Jan L.
dc.contributor.author
Stoffel, Markus
dc.contributor.author
Daly, Mark J.
dc.contributor.author
Altshuler, David M.
dc.contributor.author
Friedman, Jeffrey M.
dc.date.accessioned
2018-10-31T15:26:13Z
dc.date.available
2017-06-08T20:39:09Z
dc.date.available
2018-10-31T15:26:13Z
dc.date.issued
2009-02-06
dc.identifier.issn
1553-7390
dc.identifier.issn
1553-7404
dc.identifier.other
10.1371/journal.pgen.1000365
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/12541
dc.identifier.doi
10.3929/ethz-b-000012541
dc.description.abstract
It has been argued that the limited genetic diversity and reduced allelic heterogeneity observed in isolated founder populations facilitates discovery of loci contributing to both Mendelian and complex disease. A strong founder effect, severe isolation, and substantial inbreeding have dramatically reduced genetic diversity in natives from the island of Kosrae, Federated States of Micronesia, who exhibit a high prevalence of obesity and other metabolic disorders. We hypothesized that genetic drift and possibly natural selection on Kosrae might have increased the frequency of previously rare genetic variants with relatively large effects, making these alleles readily detectable in genome-wide association analysis. However, mapping in large, inbred cohorts introduces analytic challenges, as extensive relatedness between subjects violates the assumptions of independence upon which traditional association test statistics are based. We performed genome-wide association analysis for 15 quantitative traits in 2,906 members of the Kosrae population, using novel approaches to manage the extreme relatedness in the sample. As positive controls, we observe association to known loci for plasma cholesterol, triglycerides, and C-reactive protein and to a compelling candidate loci for thyroid stimulating hormone and fasting plasma glucose. We show that our study is well powered to detect common alleles explaining ≥5% phenotypic variance. However, no such large effects were observed with genome-wide significance, arguing that even in such a severely inbred population, common alleles typically have modest effects. Finally, we show that a majority of common variants discovered in Caucasians have indistinguishable effect sizes on Kosrae, despite the major differences in population genetics and environment.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Public Library of Science (PLoS)
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Genome-Wide Association Studies in an Isolated Founder Population from the Pacific Island of Kosrae
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
ethz.journal.title
PLoS Genetics
ethz.journal.volume
5
en_US
ethz.journal.issue
2
en_US
ethz.journal.abbreviated
PLoS Genet
ethz.pages.start
e1000365
en_US
ethz.size
17 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.nebis
005410305
ethz.publication.place
San Francisco, CA
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02538 - Institut für Molekulare Systembiologie / Institute for Molecular Systems Biology::03710 - Hafen, Ernst / Hafen, Ernst
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02539 - Institut für Molecular Health Sciences / Institute of Molecular Health Sciences::03739 - Stoffel, Markus / Stoffel, Markus
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02538 - Institut für Molekulare Systembiologie / Institute for Molecular Systems Biology::03710 - Hafen, Ernst / Hafen, Ernst
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02539 - Institut für Molecular Health Sciences / Institute of Molecular Health Sciences::03739 - Stoffel, Markus / Stoffel, Markus
ethz.date.deposited
2017-06-08T20:39:12Z
ethz.source
ECIT
ethz.identifier.importid
imp59364c19517ce64985
ethz.ecitpid
pub:23869
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-13T07:05:07Z
ethz.rosetta.lastUpdated
2018-10-31T15:26:18Z
ethz.rosetta.versionExported
true
ethz.COinS
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