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dc.contributor.authorChan, Yingleong
dc.contributor.authorHolmen, Oddgeir L.
dc.contributor.authorHavulinna, Aki S.
dc.contributor.authorSkorpen, Frank
dc.contributor.authorKvaløy, Kirsti
dc.contributor.authorSilander, Kaisa
dc.contributor.authorNguyen, Thutrang T.
dc.contributor.authorWiller, Cristen
dc.contributor.authorBoehnke, Michael
dc.contributor.authorPerola, Markus
dc.contributor.authorPalotie, Aarno
dc.contributor.authorSalomaa, Veikko
dc.contributor.authorHveem, Kristian
dc.contributor.authorFrayling, Timothy M.
dc.contributor.authorWeedon, Michael N.
dc.contributor.authorDauber, Andrew Nahum
dc.contributor.authorVatten, Lars Johan
dc.contributor.authorHirschhorn, Joel Naom
dc.date.accessioned2013-02-15T19:31:59Z
dc.date.issued2011
dc.identifier.citationChan, Yingleong, Oddgeir L. Holmen, Andrew Dauber, Lars Vatten, Aki S. Havulinna, Frank Skorpen, Kirsti Kvaløy, et al. 2011. Common variants show predicted polygenic effects on height in the tails of the distribution, except in extremely short individuals. PLoS Genetics 7(12): e1002439.en_US
dc.identifier.issn1553-7390en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10304396
dc.description.abstractCommon genetic variants have been shown to explain a fraction of the inherited variation for many common diseases and quantitative traits, including height, a classic polygenic trait. The extent to which common variation determines the phenotype of highly heritable traits such as height is uncertain, as is the extent to which common variation is relevant to individuals with more extreme phenotypes. To address these questions, we studied 1,214 individuals from the top and bottom extremes of the height distribution (tallest and shortest \(\sim\)1.5%), drawn from \(\sim\)78,000 individuals from the HUNT and FINRISK cohorts. We found that common variants still influence height at the extremes of the distribution: common variants (49/141) were nominally associated with height in the expected direction more often than is expected by chance (p<5×10\(^{-28}\)), and the odds ratios in the extreme samples were consistent with the effects estimated previously in population-based data. To examine more closely whether the common variants have the expected effects, we calculated a weighted allele score (WAS), which is a weighted prediction of height for each individual based on the previously estimated effect sizes of the common variants in the overall population. The average WAS is consistent with expectation in the tall individuals, but was not as extreme as expected in the shortest individuals (p<0.006), indicating that some of the short stature is explained by factors other than common genetic variation. The discrepancy was more pronounced (p<10\(^{−6}\)) in the most extreme individuals (height<0.25 percentile). The results at the extreme short tails are consistent with a large number of models incorporating either rare genetic non-additive or rare non-genetic factors that decrease height. We conclude that common genetic variants are associated with height at the extremes as well as across the population, but that additional factors become more prominent at the shorter extreme.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pgen.1002439en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248463/pdf/en_US
dash.licenseLAA
dc.subjectbiologyen_US
dc.subjectgeneticsen_US
dc.subjecthuman geneticsen_US
dc.titleCommon Variants Show Predicted Polygenic Effects on Height in the Tails of the Distribution, Except in Extremely Short Individualsen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Geneticsen_US
dash.depositing.authorDauber, Andrew Nahum
dc.date.available2013-02-15T19:31:59Z
dc.identifier.doi10.1371/journal.pgen.1002439*
dash.authorsorderedfalse
dash.contributor.affiliatedDauber, Andrew Nahum
dash.contributor.affiliatedVatten, Lars Johan
dash.contributor.affiliatedHirschhorn, Joel


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