Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570,000 individuals across multiple ancestries
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
Date Issued
2018-06-18
Date Acceptance
2018-05-15
Citation
PLoS ONE, 2018, 13 (6)
ISSN
1932-6203
Publisher
Public Library of Science (PLoS)
Journal / Book Title
PLoS ONE
Volume
13
Issue
6
Copyright Statement
This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Sponsor
British Heart Foundation
Medical Research Council (MRC)
Wellcome Trust
Medical Research Council (MRC)
Action on Hearing Loss
National Institutes of Health
British Heart Foundation
Medical Research Council (MRC)
National Institute for Health Research
Imperial College Healthcare NHS Trust- BRC Funding
Grant Number
SP/04/02
G0700931
084723/Z/08/Z
G0601966
G51_Chambers
1 U01 DK085545-01
SP/13/2/30111
MR/L01341X/1
RTJ6219303-1
RDF03
Subjects
MD Multidisciplinary
General Science & Technology
Publication Status
Published
Article Number
e0198166