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A comparison of two workflows for regulome and transcriptome‐based prioritization of genetic variants associated with myocardial mass
Author(s) -
Manduchi Elisabetta,
Hemerich Daiane,
Setten Jessica,
Tragante Vinicius,
Harakalova Magdalena,
Pei Jiayi,
Williams Scott M.,
Harst Pim,
Asselbergs Folkert W.,
Moore Jason H.
Publication year - 2019
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.22215
Subject(s) - genome wide association study , single nucleotide polymorphism , computational biology , linkage disequilibrium , genetic association , genomics , workflow , biology , genetics , false discovery rate , computer science , genome , gene , genotype , database
A typical task arising from main effect analyses in a Genome Wide Association Study (GWAS) is to identify single nucleotide polymorphisms (SNPs), in linkage disequilibrium with the observed signals, that are likely causal variants and the affected genes. The affected genes may not be those closest to associating SNPs. Functional genomics data from relevant tissues are believed to be helpful in selecting likely causal SNPs and interpreting implicated biological mechanisms, ultimately facilitating prevention and treatment in the case of a disease trait. These data are typically used post GWAS analyses to fine‐map the statistically significant signals identified agnostically by testing all SNPs and applying a multiple testing correction. The number of tested SNPs is typically in the millions, so the multiple testing burden is high. Motivated by this, in this study we investigated an alternative workflow, which consists in utilizing the available functional genomics data as a first step to reduce the number of SNPs tested for association. We analyzed GWAS on electrocardiographic QRS duration using these two workflows. The alternative workflow identified more SNPs, including some residing in loci not discovered with the typical workflow. Moreover, the latter are corroborated by other reports on QRS duration. This indicates the potential value of incorporating functional genomics information at the onset in GWAS analyses.