Pleiotropic Effects of Trait-Associated Genetic Variation on DNA Methylation: Utility for Refining GWAS Loci.

American Journal of Human Genetics
Eilis HannonJonathan Mill

Abstract

Most genetic variants identified in genome-wide association studies (GWASs) of complex traits are thought to act by affecting gene regulation rather than directly altering the protein product. As a consequence, the actual genes involved in disease are not necessarily the most proximal to the associated variants. By integrating data from GWAS analyses with those from genetic studies of regulatory variation, it is possible to identify variants pleiotropically associated with both a complex trait and measures of gene regulation. In this study, we used summary-data-based Mendelian randomization (SMR), a method developed to identify variants pleiotropically associated with both complex traits and gene expression, to identify variants associated with complex traits and DNA methylation. We used large DNA methylation quantitative trait locus (mQTL) datasets generated from two different tissues (blood and fetal brain) to prioritize genes for >40 complex traits with robust GWAS data and found considerable overlap with the results of SMR analyses performed with expression QTL (eQTL) data. We identified multiple examples of variable DNA methylation associated with GWAS variants for a range of complex traits, demonstrating the utility of th...Continue Reading

Citations

Mar 27, 2018·Bioinformatics·Claudia GiambartolomeiPanos Roussos
Apr 21, 2018·Annual Review of Immunology·Holm H Uhlig, Fiona Powrie
Apr 28, 2018·Nature Genetics·Naomi R WrayUNKNOWN Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
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Sep 10, 2021·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Jingjing ZhuLang Wu

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