Imperial College London
Dr Weihua Zhang

DrWeihuaZhang

Faculty of Medicine, School of Public Health

Honorary Research Associate
 
 
 
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Contact

 

+44 (0)20 7594 1612weihua.zhang

 
 
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Location

 

165Medical SchoolSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Brazel:2019:10.1016/j.biopsych.2018.11.024,
author = {Brazel, DM and Jiang, Y and Hughey, JM and Turcot, V and Zhan, X and Gong, J and Batini, C and Weissenkampen, JD and Liu, MZ and Surendran, P and Young, R and Barnes, DR and Nielsen, SF and Rasheed, A and Samuel, M and Zhao, W and Kontto, J and Perola, M and Caslake, M and de, Craen AJM and Trompet, S and Uria-Nickelsen, M and Malarstig, A and Reily, DF and Hoek, M and Vogt, T and Jukema, JW and Sattar, N and Ford, I and Packard, CJ and Alam, DS and Majumder, AAS and Di, Angelantonio E and Chowdhury, R and Amouyel, P and Arveiler, D and Blankenberg, S and Ferrières, J and Kee, F and Kuulasmaa, K and Müller-Nurasyid, M and Veronesi, G and Virtamo, J and EPIC-CVD, Consortium and Frossard, P and Nordestgaard, BG and Saleheen, D and Danesh, J and Butterworth, AS and Howson, JMM and Erzurumluoglu, AM and Jackson, VE and Melbourne, CA and Varga, TV and Warren, HR and Tragante, V and Tachmazidou, I and Harris, SE and Evangelou, E and Marten, J and Zhang, W and Altmaier, E and Luan, J and Lang},
doi = {10.1016/j.biopsych.2018.11.024},
journal = {Biological Psychiatry},
pages = {946--955},
title = {Exome chip meta-analysis fine maps causal variants and elucidates the genetic architecture of rare coding variants in smoking and alcohol use},
url = {http://dx.doi.org/10.1016/j.biopsych.2018.11.024},
volume = {85},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background: Smoking and alcohol use have been associated with common genetic variants in multiple loci. Rare variants within these loci hold promise in the identification of biological mechanisms in substance use. Exome arrays and genotype imputation can now efficiently genotype rare nonsynonymous and loss of function variants. Such variants are expected to have deleterious functional consequences and to contribute to disease risk. Methods: We analyzed ∼250,000 rare variants from 16 independent studies genotyped with exome arrays and augmented this dataset with imputed data from the UK Biobank. Associations were tested for five phenotypes: cigarettes per day, pack-years, smoking initiation, age of smoking initiation, and alcoholic drinks per week. We conducted stratified heritability analyses, single-variant tests, and gene-based burden tests of nonsynonymous/loss-of-function coding variants. We performed a novel fine-mapping analysis to winnow the number of putative causal variants within associated loci. Results: Meta-analytic sample sizes ranged from 152,348 to 433,216, depending on the phenotype. Rare coding variation explained 1.1% to 2.2% of phenotypic variance, reflecting 11% to 18% of the total single nucleotide polymorphism heritability of these phenotypes. We identified 171 genome-wide associated loci across all phenotypes. Fine mapping identified putative causal variants with double base-pair resolution at 24 of these loci, and between three and 10 variants for 65 loci. Twenty loci contained rare coding variants in the 95% credible intervals. Conclusions: Rare coding variation significantly contributes to the heritability of smoking and alcohol use. Fine-mapping genome-wide association study loci identifies specific variants contributing to the biological etiology of substance use behavior.
AU  - Brazel,DM
AU  - Jiang,Y
AU  - Hughey,JM
AU  - Turcot,V
AU  - Zhan,X
AU  - Gong,J
AU  - Batini,C
AU  - Weissenkampen,JD
AU  - Liu,MZ
AU  - Surendran,P
AU  - Young,R
AU  - Barnes,DR
AU  - Nielsen,SF
AU  - Rasheed,A
AU  - Samuel,M
AU  - Zhao,W
AU  - Kontto,J
AU  - Perola,M
AU  - Caslake,M
AU  - de,Craen AJM
AU  - Trompet,S
AU  - Uria-Nickelsen,M
AU  - Malarstig,A
AU  - Reily,DF
AU  - Hoek,M
AU  - Vogt,T
AU  - Jukema,JW
AU  - Sattar,N
AU  - Ford,I
AU  - Packard,CJ
AU  - Alam,DS
AU  - Majumder,AAS
AU  - Di,Angelantonio E
AU  - Chowdhury,R
AU  - Amouyel,P
AU  - Arveiler,D
AU  - Blankenberg,S
AU  - Ferrières,J
AU  - Kee,F
AU  - Kuulasmaa,K
AU  - Müller-Nurasyid,M
AU  - Veronesi,G
AU  - Virtamo,J
AU  - EPIC-CVD,Consortium
AU  - Frossard,P
AU  - Nordestgaard,BG
AU  - Saleheen,D
AU  - Danesh,J
AU  - Butterworth,AS
AU  - Howson,JMM
AU  - Erzurumluoglu,AM
AU  - Jackson,VE
AU  - Melbourne,CA
AU  - Varga,TV
AU  - Warren,HR
AU  - Tragante,V
AU  - Tachmazidou,I
AU  - Harris,SE
AU  - Evangelou,E
AU  - Marten,J
AU  - Zhang,W
AU  - Altmaier,E
AU  - Luan,J
AU  - Langenberg,C
AU  - Scott,RA
AU  - Yaghootkar,H
AU  - Stirrups,K
AU  - Kanoni,S
AU  - Marouli,E
AU  - Karpe,F
AU  - Dominiczak,AF
AU  - Sever,P
AU  - Poulter,N
AU  - Rolandsson,O
AU  - Baumbach,C
AU  - Afaq,S
AU  - Chambers,JC
AU  - Kooner,JS
AU  - Wareham,NJ
AU  - Renström,F
AU  - Hallmans,G
AU  - Marioni,RE
AU  - Corley,J
AU  - Starr,JM
AU  - Verweij,N
AU  - de,Boer RA
AU  - van,der Meer P
AU  - Yavas,E
AU  - Vaartjes,I
AU  - Bots,ML
AU  - Asselbergs,FW
AU  - Grabe,HJ
AU  - Völzke,H
DO  - 10.1016/j.biopsych.2018.11.024
EP  - 955
PY  - 2019///
SN  - 0006-3223
SP  - 946
TI  - Exome chip meta-analysis fine maps causal variants and elucidates the genetic architecture of rare coding variants in smoking and alcohol use
T2  - Biological Psychiatry
UR  - http://dx.doi.org/10.1016/j.biopsych.2018.11.024
UR  - https://www.sciencedirect.com/science/article/pii/S0006322318320560?via%3Dihub
VL  - 85
ER  -
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