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A large-scale multi-ancestry genome-wide study accounting for smoking bahavior identifies multiple genome-wide significant loci for systolic and diastolic blood pressure

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Title: A large-scale multi-ancestry genome-wide study accounting for smoking bahavior identifies multiple genome-wide significant loci for systolic and diastolic blood pressure
Authors: Sung, YJ
Lehne, B
Scott, WR
Sever, P
Chambers, J
Froguel, P
Kooner, JS
Scott, J
Elliott, P
Chasman, DI
Item Type: Journal Article
Abstract: Genome- wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify novel BP loci and extend our knowledge of its genetic architecture. We performed genome -wide association meta -analys es of systolic and diastolic BP incorporating gene -smoking interactions in 610,091 individuals . Stage 1 analysis examined ~18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow -up analysis of promising variants in 480 ,178 additional individuals from fiv e ancestr ies . We identifie d 15 new loci that were genome- wide significant (P < 5 ×10 -8 ) in Stage 1 and formally replicated in Stage 2 . A combined Stage 1 and 2 meta -analysis identified 66 additional genome - wide significant loci ( 13, 35, and 18 loci in European, African and trans -ancestry, respectively ). A total of 5 6 k nown BP loci were also identified by our results (P < 5 ×10 -8 ). O f the newly identified loci , 10 sho wed significant interaction with smoking status , but none of them were replicated in Stage 2 . Several loci were identified in African ancestry , highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with c ardiometabolic and addiction traits . They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function ( CDKN1B , BCAR1 -CFDP1 , PXDN , EEA1 ), ciliopathies ( SDCCAG8, RPGRIP1L ), telomere maintenance ( TNKS , PINX1 , AKTIP ) , and cen tral dopaminergic signaling ( MSRA , EBF2 )
Issue Date: 15-Feb-2018
Date of Acceptance: 18-Jan-2018
URI: http://hdl.handle.net/10044/1/56672
DOI: https://dx.doi.org/10.1016/j.ajhg.2018.01.015
ISSN: 0002-9297
Publisher: Elsevier (Cell Press)
Start Page: 375
End Page: 400
Journal / Book Title: American Journal of Human Genetics
Volume: 102
Issue: 3
Copyright Statement: © 2018 American Society of Human Genetics. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Sponsor/Funder: British Heart Foundation
Medical Research Council (MRC)
Wellcome Trust
Medical Research Council (MRC)
Action on Hearing Loss
Home Office
British Heart Foundation
Medical Research Council (MRC)
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
7370192
SP/13/2/30111
MR/L01632X/1
MR/L01341X/1
RTJ6219303-1
RDF03
Keywords: GWAS
GxE interactions
blood pressure
lifestyle
multi-ancestry
smoking
06 Biological Sciences
11 Medical And Health Sciences
Genetics & Heredity
Publication Status: Published
Article Number: AJHG-D-17-00640R4
Appears in Collections:National Heart and Lung Institute
Epidemiology, Public Health and Primary Care



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