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Common variants show predicted polygenic effects on height in the tails of the distribution,except in extremely short individuals
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نویسنده
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chan y. ,holmen o.l. ,dauber a. ,vatten l. ,havulinna a.s. ,skorpen f. ,kvaløy k. ,silander k. ,nguyen t.t. ,willer c. ,boehnke m. ,perola m. ,palotie a. ,salomaa v. ,hveem k. ,frayling t.m. ,hirschhorn j.n. ,weedon m.n.
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منبع
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plos genetics - 2011 - دوره : 7 - شماره : 12
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چکیده
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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 ~1.5%),drawn from ~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. © 2011 chan et al.
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آدرس
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department of genetics,harvard medical school,boston,ma,united states,broad institute,cambridge,ma,united states,children's hospital boston,boston,ma, United States, hunt research centre,department of public health and general practice,norwegian university of science and technology,levanger,norway,st. olav hospital,trondheim university hospital,trondheim, Norway, broad institute,cambridge,ma,united states,children's hospital boston,boston,ma, United States, department of public health and general practice,norwegian university of science and technology,trondheim, Norway, national institute for health and welfare,helsinki, Finland, department of laboratory medicine,children's and women's health,norwegian university of science and technology,trondheim, Norway, hunt research centre,department of public health and general practice,norwegian university of science and technology,levanger, Norway, national institute for health and welfare,helsinki,finland,institute for molecular medicine finland (fimm),university of helsinki,helsinki, Finland, children's hospital boston,boston,ma, United States, department of internal medicine,division of cardiovascular medicine,university of michigan,ann arbor,mi, United States, department of internal medicine,division of cardiovascular medicine,university of michigan,ann arbor,mi, United States, national institute for health and welfare,helsinki,finland,institute for molecular medicine finland (fimm),university of helsinki,helsinki,finland,estonian genome project,university of tartu,tartu, Estonia, broad institute,cambridge,ma,united states,institute for molecular medicine finland (fimm),university of helsinki,helsinki,finland,wellcome trust sanger institute,wellcome trust genome campus,hinxton,united kingdom,department of medical genetics,university of helsinki and university central hospital,helsinki, Finland, national institute for health and welfare,helsinki, Finland, hunt research centre,department of public health and general practice,norwegian university of science and technology,levanger, Norway, genetics of complex traits,peninsula medical school,university of exeter,exeter, United Kingdom, department of genetics,harvard medical school,boston,ma,united states,broad institute,cambridge,ma,united states,children's hospital boston,boston,ma, United States, genetics of complex traits,peninsula medical school,university of exeter,exeter, United Kingdom
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Authors
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