Altmetric

Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570,000 individuals across multiple ancestries

File Description SizeFormat 
journal.pone.0198166.pdfPublished version2.16 MBAdobe PDFView/Open
Title: Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570,000 individuals across multiple ancestries
Authors: Feitosa, M
Kraja, A
Zhang, W
Evangelou, E
Gao, H
Scott, W
Sever, P
Chambers, J
Froguel, P
Scott, J
Elliott, P
Levy, D
Item 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.
Issue Date: 18-Jun-2018
Date of Acceptance: 15-May-2018
URI: http://hdl.handle.net/10044/1/60306
DOI: https://dx.doi.org/10.1371/journal.pone.0198166
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/Funder: 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
Funder's 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
Keywords: MD Multidisciplinary
General Science & Technology
Publication Status: Published
Article Number: e0198166
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commonsx