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An atlas of polygenic risk score associations to highlight putative causal relationships across the human phenome
The age of large-scale genome-wide association studies (GWAS) has provided us with an unprecedented opportunity to evaluate the genetic liability of complex disease using polygenic risk scores (PRS). In this study, we have analysed 162 PRS (p<5×10(−05)) derived from GWAS and 551 heritable traits...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400585/ https://www.ncbi.nlm.nih.gov/pubmed/30835202 http://dx.doi.org/10.7554/eLife.43657 |
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author | Richardson, Tom G Harrison, Sean Hemani, Gibran Davey Smith, George |
author_facet | Richardson, Tom G Harrison, Sean Hemani, Gibran Davey Smith, George |
author_sort | Richardson, Tom G |
collection | PubMed |
description | The age of large-scale genome-wide association studies (GWAS) has provided us with an unprecedented opportunity to evaluate the genetic liability of complex disease using polygenic risk scores (PRS). In this study, we have analysed 162 PRS (p<5×10(−05)) derived from GWAS and 551 heritable traits from the UK Biobank study (N = 334,398). Findings can be investigated using a web application (http://mrcieu.mrsoftware.org/PRS_atlas/), which we envisage will help uncover both known and novel mechanisms which contribute towards disease susceptibility. To demonstrate this, we have investigated the results from a phenome-wide evaluation of schizophrenia genetic liability. Amongst findings were inverse associations with measures of cognitive function which extensive follow-up analyses using Mendelian randomization (MR) provided evidence of a causal relationship. We have also investigated the effect of multiple risk factors on disease using mediation and multivariable MR frameworks. Our atlas provides a resource for future endeavours seeking to unravel the causal determinants of complex disease. |
format | Online Article Text |
id | pubmed-6400585 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-64005852019-03-07 An atlas of polygenic risk score associations to highlight putative causal relationships across the human phenome Richardson, Tom G Harrison, Sean Hemani, Gibran Davey Smith, George eLife Genetics and Genomics The age of large-scale genome-wide association studies (GWAS) has provided us with an unprecedented opportunity to evaluate the genetic liability of complex disease using polygenic risk scores (PRS). In this study, we have analysed 162 PRS (p<5×10(−05)) derived from GWAS and 551 heritable traits from the UK Biobank study (N = 334,398). Findings can be investigated using a web application (http://mrcieu.mrsoftware.org/PRS_atlas/), which we envisage will help uncover both known and novel mechanisms which contribute towards disease susceptibility. To demonstrate this, we have investigated the results from a phenome-wide evaluation of schizophrenia genetic liability. Amongst findings were inverse associations with measures of cognitive function which extensive follow-up analyses using Mendelian randomization (MR) provided evidence of a causal relationship. We have also investigated the effect of multiple risk factors on disease using mediation and multivariable MR frameworks. Our atlas provides a resource for future endeavours seeking to unravel the causal determinants of complex disease. eLife Sciences Publications, Ltd 2019-03-05 /pmc/articles/PMC6400585/ /pubmed/30835202 http://dx.doi.org/10.7554/eLife.43657 Text en © 2019, Richardson et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Genetics and Genomics Richardson, Tom G Harrison, Sean Hemani, Gibran Davey Smith, George An atlas of polygenic risk score associations to highlight putative causal relationships across the human phenome |
title | An atlas of polygenic risk score associations to highlight putative causal relationships across the human phenome |
title_full | An atlas of polygenic risk score associations to highlight putative causal relationships across the human phenome |
title_fullStr | An atlas of polygenic risk score associations to highlight putative causal relationships across the human phenome |
title_full_unstemmed | An atlas of polygenic risk score associations to highlight putative causal relationships across the human phenome |
title_short | An atlas of polygenic risk score associations to highlight putative causal relationships across the human phenome |
title_sort | atlas of polygenic risk score associations to highlight putative causal relationships across the human phenome |
topic | Genetics and Genomics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400585/ https://www.ncbi.nlm.nih.gov/pubmed/30835202 http://dx.doi.org/10.7554/eLife.43657 |
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