{"id":6903,"date":"2017-08-14T05:12:38","date_gmt":"2017-08-14T04:12:38","guid":{"rendered":"http:\/\/emilkirkegaard.dk\/en\/?p=6903"},"modified":"2017-08-14T05:12:38","modified_gmt":"2017-08-14T04:12:38","slug":"estimating-the-polygenicity-of-traits-an-update","status":"publish","type":"post","link":"https:\/\/emilkirkegaard.dk\/en\/2017\/08\/estimating-the-polygenicity-of-traits-an-update\/","title":{"rendered":"Estimating the polygenicity of traits: an update"},"content":{"rendered":"<p>Readers will perhaps recall that I tried to come up with some metrics for the polygenicity of a trait <a href=\"http:\/\/emilkirkegaard.dk\/en\/?p=5760\">back in 2016<\/a>. Well, there&#8217;s a new preprint now:<\/p>\n<p><a href=\"http:\/\/www.biorxiv.org\/content\/early\/2017\/08\/11\/175406\"><strong>Estimation of complex effect-size distributions using summary-level statistics from genome-wide association studies across 32 complex traits and implications for the future<\/strong><\/a><\/p>\n<blockquote><p>Summary-level statistics from genome-wide association studies are now widely used to estimate heritability and co-heritability of traits using the popular linkage-disequilibrium-score (LD-score) regression method. We develop a likelihood-based approach for analyzing summary-level statistics and external LD information to estimate common variants effect-size distributions, characterized by proportion of underlying susceptibility SNPs and a flexible normal-mixture model for their effects. Analysis of summary-level results across 32 GWAS reveals that while all traits are highly polygenic, there is wide diversity in the degrees of polygenicity. The effect-size distributions for susceptibility SNPs could be adequately modeled by a single normal distribution for traits related to mental health and ability and by a mixture of two normal distributions for all other traits. Among quantitative traits, we predict the sample sizes needed to identify SNPs which explain 80% of GWAS heritability to be between 300K-500K for some of the early growth traits, between 1-2 million for some anthropometric and cholesterol traits and multiple millions for body mass index and some others. The corresponding predictions for disease traits are between 200K-400K for inflammatory bowel diseases, close to one million for a variety of adult onset chronic diseases and between 1-2 million for psychiatric diseases.<\/p><\/blockquote>\n<p>See also <a href=\"https:\/\/arxiv.org\/abs\/1408.3421\">Hsu&#8217;s 2014 paper<\/a> on the same topic, attacking the problem from another angle.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Readers will perhaps recall that I tried to come up with some metrics for the polygenicity of a trait back in 2016. Well, there&#8217;s a new preprint now: Estimation of complex effect-size distributions using summary-level statistics from genome-wide association studies across 32 complex traits and implications for the future Summary-level statistics from genome-wide association studies [&hellip;]<\/p>\n","protected":false},"author":17,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[2463],"tags":[2522],"class_list":["post-6903","post","type-post","status-publish","format-standard","hentry","category-genomics","tag-polygenicity","entry"],"_links":{"self":[{"href":"https:\/\/emilkirkegaard.dk\/en\/wp-json\/wp\/v2\/posts\/6903","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/emilkirkegaard.dk\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/emilkirkegaard.dk\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/emilkirkegaard.dk\/en\/wp-json\/wp\/v2\/users\/17"}],"replies":[{"embeddable":true,"href":"https:\/\/emilkirkegaard.dk\/en\/wp-json\/wp\/v2\/comments?post=6903"}],"version-history":[{"count":1,"href":"https:\/\/emilkirkegaard.dk\/en\/wp-json\/wp\/v2\/posts\/6903\/revisions"}],"predecessor-version":[{"id":6904,"href":"https:\/\/emilkirkegaard.dk\/en\/wp-json\/wp\/v2\/posts\/6903\/revisions\/6904"}],"wp:attachment":[{"href":"https:\/\/emilkirkegaard.dk\/en\/wp-json\/wp\/v2\/media?parent=6903"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/emilkirkegaard.dk\/en\/wp-json\/wp\/v2\/categories?post=6903"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/emilkirkegaard.dk\/en\/wp-json\/wp\/v2\/tags?post=6903"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}