A Bayesian framework for multiple trait colocalization from summary association statistics

Bioinformatics
Claudia GiambartolomeiPanos Roussos

Abstract

Most genetic variants implicated in complex diseases by genome-wide association studies (GWAS) are non-coding, making it challenging to understand the causative genes involved in disease. Integrating external information such as quantitative trait locus (QTL) mapping of molecular traits (e.g. expression, methylation) is a powerful approach to identify the subset of GWAS signals explained by regulatory effects. In particular, expression QTLs (eQTLs) help pinpoint the responsible gene among the GWAS regions that harbor many genes, while methylation QTLs (mQTLs) help identify the epigenetic mechanisms that impact gene expression which in turn affect disease risk. In this work, we propose multiple-trait-coloc (moloc), a Bayesian statistical framework that integrates GWAS summary data with multiple molecular QTL data to identify regulatory effects at GWAS risk loci. We applied moloc to schizophrenia (SCZ) and eQTL/mQTL data derived from human brain tissue and identified 52 candidate genes that influence SCZ through methylation. Our method can be applied to any GWAS and relevant functional data to help prioritize disease associated genes. Availability and implementation: moloc is available for download as an R package (https://github...Continue Reading

References

Apr 7, 2018·Current Psychiatry Reports·Nikolaos P DaskalakisKerry J Ressler
Dec 21, 2019·Bioinformatics·Gittu GeorgeAlex S F Doney
Apr 11, 2020·PLoS Computational Biology·Yangqing Deng, Wei Pan
Oct 12, 2019·Brain : a Journal of Neurology·Regina H ReynoldsSarah A Gagliano Taliun
Oct 7, 2020·International Journal of Molecular Sciences·Ashley HallKimberley J Billingsley
Aug 11, 2020·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Douglas P KielNoel Burtt

Citations

Sep 19, 2009·Nature Reviews. Genetics·Matthew Stephens, David J Balding
Jan 17, 2012·American Journal of Human Genetics·Peter M VisscherJian Yang
Apr 8, 2014·American Journal of Human Genetics·Joseph K Pickrell
Jul 25, 2014·Nature·Schizophrenia Working Group of the Psychiatric Genomics Consortium
Sep 29, 2015·Nature Genetics·Brendan Bulik-SullivanBenjamin M Neale
Dec 1, 2015·Nature Neuroscience·Eilis HannonJonathan Mill
Jan 26, 2016·PLoS Computational Biology·David LamparterSven Bergmann
Apr 30, 2016·Science·Yang I LiJonathan K Pritchard
May 18, 2016·Nature Genetics·Joseph K PickrellDavid A Hinds
Oct 28, 2016·Nature Neuroscience·Menachem FromerPamela Sklar
Nov 22, 2016·American Journal of Human Genetics·Farhad HormozdiariEleazar Eskin
May 23, 2017·American Journal of Human Genetics·Eilis HannonJonathan Mill
May 30, 2017·American Journal of Human Genetics·Mads E HaubergPanos Roussos

Related Concepts

Quantitative Trait Loci
Protein Methylation
Genes
Candidate Disease Gene
Bio-Informatics
Gene Expression
SCHIZORIZA protein, Arabidopsis
Study of Epigenetics
Methylation
Citrus macrophylla

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