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@ARTICLE{Brazel:144043,
author = {D. M. Brazel and Y. Jiang and J. M. Hughey and V. Turcot
and X. Zhan and J. Gong and C. Batini and J. D.
Weissenkampen and M. Liu and D. R. Barnes and S. Bertelsen
and Y.-L. Chou and A. M. Erzurumluoglu and J. D. Faul and J.
Haessler and A. R. Hammerschlag and C. Hsu and M. Kapoor and
D. Lai and N. Le and C. A. de Leeuw and A. Loukola and M.
Mangino and C. A. Melbourne and G. Pistis and B. Qaiser and
R. Rohde and Y. Shao and H. Stringham and L. Wetherill and
W. Zhao and A. Agrawal and L. Bierut and C. Chen and C. B.
Eaton and A. Goate and C. Haiman and A. Heath and W. G.
Iacono and N. G. Martin and T. J. Polderman and A. Reiner
and J. Rice and D. Schlessinger and H. S. Scholte and J. A.
Smith and J.-C. Tardif and H. A. Tindle and A. R. van der
Leij and M. Boehnke and J. Chang-Claude$^*$ and F. Cucca and
S. P. David and T. Foroud and J. M. M. Howson and S. L. R.
Kardia and C. Kooperberg and M. Laakso and G. Lettre and P.
Madden and M. McGue and K. North and D. Posthuma and T.
Spector and D. Stram and M. D. Tobin and D. R. Weir and J.
Kaprio and G. R. Abecasis and D. J. Liu and S. Vrieze and P.
Surendran and R. Young and D. R. Barnes and S. F. Nielsen
and A. Rasheed and M. Samuel and W. Zhao and J. Kontto and
M. Perola and M. Caslake and A. J. M. de Craen and S.
Trompet and M. Uria-Nickelsen and A. Malarstig and D. F.
Reily and M. Hoek and T. Vogt and J. W. Jukema and N. Sattar
and I. Ford and C. J. Packard and D. S. Alam and A. A. S.
Majumder and E. Di Angelantonio and R. Chowdhury and P.
Amouyel and D. Arveiler and S. Blankenberg and J. Ferrières
and F. Kee and K. Kuulasmaa and M. Müller-Nurasyid and G.
Veronesi and J. Virtamo and Epic-Cvd Consortium and P.
Frossard and B. G. Nordestgaard and D. Saleheen and J.
Danesh and A. S. Butterworth and J. M. M. Howson and A. M.
Erzurumluoglu and V. E. Jackson and C. A. Melbourne and T.
V. Varga and H. R. Warren and V. Tragante and I. Tachmazidou
and S. E. Harris and E. Evangelou and J. Marten and W. Zhang
and E. Altmaier and J. Luan and C. Langenberg and R. A.
Scott and H. Yaghootkar and K. Stirrups and S. Kanoni and E.
Marouli and F. Karpe and A. F. Dominiczak and P. Sever and
N. Poulter and O. Rolandsson and C. Baumbach and S. Afaq and
J. C. Chambers and J. S. Kooner and N. J. Wareham and F.
Renström and G. Hallmans and R. E. Marioni and J. Corley
and J. M. Starr and N. Verweij and R. A. de Boer and P. van
der Meer and E. Yavas and I. Vaartjes and M. L. Bots and F.
W. Asselbergs and H. J. Grabe and H. Völzke and M. Nauck
and S. Weiss and P. D. P. Pharoah and A. M. Dunning and J.
G. Dennis and D. J. Thompson and K. Michailidou and D. F.
Easton and A. C. Antoniou and J. Tyrrell and E. Mihailov and
N. J. Samani and K. Zhou and M. J. Neville and A. Metspalu
and C. N. A. Palmer and I. P. Hall and D. P. Strachan and I.
J. Deary and T. M. Frayling and C. Hayward and P. van der
Harst and E. Zeggini and Understanding Society Scientific
Group and P. B. Munroe and J.-H. Jansson and P. W. Franks
and P. Deloukas and M. J. Caulfield and L. V. Wain and M. D.
Tobin},
collaboration = {C. E. Consortium and C. f. G. o. S. Behaviour},
title = {{E}xome {C}hip {M}eta-analysis {F}ine {M}aps {C}ausal
{V}ariants and {E}lucidates the {G}enetic {A}rchitecture of
{R}are {C}oding {V}ariants in {S}moking and
{A}lcohol {U}se.},
journal = {Biological psychiatry},
volume = {85},
number = {11},
issn = {0006-3223},
address = {Amsterdam [u.a.]},
publisher = {Elsevier Science},
reportid = {DKFZ-2019-01594},
pages = {946 - 955},
year = {2019},
abstract = {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.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.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.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.},
cin = {C020},
ddc = {610},
cid = {I:(DE-He78)C020-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30679032},
pmc = {pmc:PMC6534468},
doi = {10.1016/j.biopsych.2018.11.024},
url = {https://inrepo02.dkfz.de/record/144043},
}