Common Variants Show Predicted Polygenic Effects on Height in the Tails of the Distribution, Except in Extremely Short Individuals
View/ Open
Author
Chan, Yingleong
Holmen, Oddgeir L.
Havulinna, Aki S.
Skorpen, Frank
Kvaløy, Kirsti
Silander, Kaisa
Nguyen, Thutrang T.
Willer, Cristen
Boehnke, Michael
Perola, Markus
Palotie, Aarno
Salomaa, Veikko
Hveem, Kristian
Frayling, Timothy M.
Weedon, Michael N.
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1371/journal.pgen.1002439Metadata
Show full item recordCitation
Chan, 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.Abstract
Common 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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248463/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:10304396
Collections
- HMS Scholarly Articles [17918]
Contact administrator regarding this item (to report mistakes or request changes)