Linkage disequilibrium dependent architecture of human complex traits reveals action of negative selection
<p>Recent work has hinted at the linkage disequilibrium (LD)-dependent architecture of human complex traits, where SNPs with low levels of LD (LLD) have larger per-SNP heritability. Here we analyzed summary statistics from 56 complex traits (average <em>N</em> = 101,401) by extendi...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal article |
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Springer Nature
2017
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| _version_ | 1826258099147636736 |
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| author | Gazal, S Finucane, H Furlotte, N Loh, P Palamara, P Liu, X Schoech, A Bulik-Sullivan, B Neale, B Gusev, A Price, A |
| author_facet | Gazal, S Finucane, H Furlotte, N Loh, P Palamara, P Liu, X Schoech, A Bulik-Sullivan, B Neale, B Gusev, A Price, A |
| author_sort | Gazal, S |
| collection | OXFORD |
| description | <p>Recent work has hinted at the linkage disequilibrium (LD)-dependent architecture of human complex traits, where SNPs with low levels of LD (LLD) have larger per-SNP heritability. Here we analyzed summary statistics from 56 complex traits (average <em>N</em> = 101,401) by extending stratified LD score regression to continuous annotations. We determined that SNPs with low LLD have significantly larger per-SNP heritability and that roughly half of this effect can be explained by functional annotations negatively correlated with LLD, such as DNase I hypersensitivity sites (DHSs). The remaining signal is largely driven by our finding that more recent common variants tend to have lower LLD and to explain more heritability (<em>P</em> = 2.38 × 10<sup>−104</sup>); the youngest 20% of common SNPs explain 3.9 times more heritability than the oldest 20%, consistent with the action of negative selection. We also inferred jointly significant effects of other LD-related annotations and confirmed via forward simulations that they jointly predict deleterious effects.</p> |
| first_indexed | 2024-03-06T18:28:40Z |
| format | Journal article |
| id | oxford-uuid:08deea57-d220-4b94-99b5-1e68dfca7278 |
| institution | University of Oxford |
| last_indexed | 2024-03-06T18:28:40Z |
| publishDate | 2017 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:08deea57-d220-4b94-99b5-1e68dfca72782022-03-26T09:15:16ZLinkage disequilibrium dependent architecture of human complex traits reveals action of negative selectionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:08deea57-d220-4b94-99b5-1e68dfca7278Symplectic Elements at OxfordSpringer Nature2017Gazal, SFinucane, HFurlotte, NLoh, PPalamara, PLiu, XSchoech, ABulik-Sullivan, BNeale, BGusev, APrice, A<p>Recent work has hinted at the linkage disequilibrium (LD)-dependent architecture of human complex traits, where SNPs with low levels of LD (LLD) have larger per-SNP heritability. Here we analyzed summary statistics from 56 complex traits (average <em>N</em> = 101,401) by extending stratified LD score regression to continuous annotations. We determined that SNPs with low LLD have significantly larger per-SNP heritability and that roughly half of this effect can be explained by functional annotations negatively correlated with LLD, such as DNase I hypersensitivity sites (DHSs). The remaining signal is largely driven by our finding that more recent common variants tend to have lower LLD and to explain more heritability (<em>P</em> = 2.38 × 10<sup>−104</sup>); the youngest 20% of common SNPs explain 3.9 times more heritability than the oldest 20%, consistent with the action of negative selection. We also inferred jointly significant effects of other LD-related annotations and confirmed via forward simulations that they jointly predict deleterious effects.</p> |
| spellingShingle | Gazal, S Finucane, H Furlotte, N Loh, P Palamara, P Liu, X Schoech, A Bulik-Sullivan, B Neale, B Gusev, A Price, A Linkage disequilibrium dependent architecture of human complex traits reveals action of negative selection |
| title | Linkage disequilibrium dependent architecture of human complex traits reveals action of negative selection |
| title_full | Linkage disequilibrium dependent architecture of human complex traits reveals action of negative selection |
| title_fullStr | Linkage disequilibrium dependent architecture of human complex traits reveals action of negative selection |
| title_full_unstemmed | Linkage disequilibrium dependent architecture of human complex traits reveals action of negative selection |
| title_short | Linkage disequilibrium dependent architecture of human complex traits reveals action of negative selection |
| title_sort | linkage disequilibrium dependent architecture of human complex traits reveals action of negative selection |
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