Reducing GWAS Complexity

Cell Cycle
Dennis J HazelettGerhard A Coetzee

Abstract

Genome-wide association studies (GWAS) have revealed numerous genomic 'hits' associated with complex phenotypes. In most cases these hits, along with surrogate genetic variation as measure by numerous single nucleotide polymorphisms (SNPs) that are in linkage disequilibrium, are not in coding genes making assignment of functionality or causality intractable. Here we propose that fine-mapping along with the matching of risk SNPs at chromatin biofeatures lessen this complexity by reducing the number of candidate functional/causal SNPs. For example, we show here that only on average 2 SNPs per prostate cancer risk locus are likely candidates for functionality/causality; we further propose that this manageable number should be taken forward in mechanistic studies. The candidate SNPs can be looked up for each prostate cancer risk region in 2 recent publications in 2015 (1,2) from our groups.

References

Aug 2, 2007·American Journal of Human Genetics·Jon Wakefield
Jul 6, 2010·Nucleic Acids Research·Kai WangHakon Hakonarson
Jan 12, 2011·Nature Biotechnology·James T RobinsonJill P Mesirov
Sep 8, 2012·Genome Research·Alan P BoyleMichael Snyder
May 30, 2013·PloS One·Suhn Kyong RhieGerhard A Coetzee
Jul 5, 2013·Statistics in Medicine·M A Quintana, D V Conti
Feb 6, 2014·PLoS Genetics·Dennis J HazelettGerhard A Coetzee
Aug 12, 2014·Genetics·Farhad HormozdiariEleazar Eskin
Mar 26, 2015·Human Molecular Genetics·Simon G CoetzeeUNKNOWN Ovarian Cancer Association Consortium The Consortium of Investigators of Modifiers of BRCA1/2

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Citations

May 15, 2018·PloS One·Anette Tarp HansenMette Christiansen
Mar 29, 2019·Journal of Animal Science and Biotechnology·Mahmuda Bilkis Bintee AlamShuhong Zhao
Dec 20, 2017·Journal of Parkinson's Disease·Gerhard A Coetzee, Steven Pierce
Sep 24, 2020·NPJ Parkinson's Disease·Steven E PierceGerhard A Coetzee

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Methods Mentioned

BETA
ChIP-seq

Software Mentioned

FunSeq
Haploreg
Annovar
IGV
FunciSNP
RegulomeDB
motifbreakR

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