Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
21529783
TITLE
A quantitative-trait genome-wide association study of alcoholism risk in the community: findings and implications.
ABSTRACT
BACKGROUND NlmCategory: BACKGROUND
Given moderately strong genetic contributions to variation in alcoholism and heaviness of drinking (50% to 60% heritability) with high correlation of genetic influences, we have conducted a quantitative trait genome-wide association study (GWAS) for phenotypes related to alcohol use and dependence.
METHODS NlmCategory: METHODS
Diagnostic interview and blood/buccal samples were obtained from sibships ascertained through the Australian Twin Registry. Genome-wide single nucleotide polymorphism (SNP) genotyping was performed with 8754 individuals (2062 alcohol-dependent cases) selected for informativeness for alcohol use disorder and associated quantitative traits. Family-based association tests were performed for alcohol dependence, dependence factor score, and heaviness of drinking factor score, with confirmatory case-population control comparisons using an unassessed population control series of 3393 Australians with genome-wide SNP data.
RESULTS NlmCategory: RESULTS
No findings reached genome-wide significance (p = 8.4 × 10(-8) for this study), with lowest p value for primary phenotypes of 1.2 × 10(-7). Convergent findings for quantitative consumption and diagnostic and quantitative dependence measures suggest possible roles for a transmembrane protein gene (TMEM108) and for ANKS1A. The major finding, however, was small effect sizes estimated for individual SNPs, suggesting that hundreds of genetic variants make modest contributions (1/4% of variance or less) to alcohol dependence risk.
CONCLUSIONS NlmCategory: CONCLUSIONS
We conclude that 1) meta-analyses of consumption data may contribute usefully to gene discovery; 2) translation of human alcoholism GWAS results to drug discovery or clinically useful prediction of risk will be challenging; and 3) through accumulation across studies, GWAS data may become valuable for improved genetic risk differentiation in research in biological psychiatry (e.g., prospective high-risk or resilience studies).
Copyright 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
DATE PUBLISHED
2011 Sep 15
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2010/06/29
revised 2011/01/26
accepted 2011/02/17
aheadofprint 2011/05/06
entrez 2011/05/03 06:00
pubmed 2011/05/03 06:00
medline 2012/01/10 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Heath AC Heath Andrew C AC Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA. aheath@wustl.edu
Whitfield JB Whitfield John B JB
Martin NG Martin Nicholas G NG
Pergadia ML Pergadia Michele L ML
Goate AM Goate Alison M AM
Lind PA Lind Penelope A PA
McEvoy BP McEvoy Brian P BP
Schrage AJ Schrage Andrew J AJ
Grant JD Grant Julia D JD
Chou YL Chou Yi-Ling YL
Zhu R Zhu Rachel R
Henders AK Henders Anjali K AK
Medland SE Medland Sarah E SE
Gordon SD Gordon Scott D SD
Nelson EC Nelson Elliot C EC
Agrawal A Agrawal Arpana A
Nyholt DR Nyholt Dale R DR
Bucholz KK Bucholz Kathleen K KK
Madden PA Madden Pamela A F PA
Montgomery GW Montgomery Grant W GW
INVESTIGATORS
JOURNAL
VOLUME: 70
ISSUE: 6
TITLE: Biological psychiatry
ISOABBREVIATION: Biol. Psychiatry
YEAR: 2011
MONTH: Sep
DAY: 15
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1873-2402
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Biol Psychiatry
COUNTRY: United States
ISSNLINKING: 0006-3223
NLMUNIQUEID: 0213264
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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CommentIn Biol Psychiatry. 2011 Sep 15;70(6):498-9 21864733
GRANTS
GRANTID AGENCY COUNTRY
AA07535 NIAAA NIH HHS United States
AA07728 NIAAA NIH HHS United States
AA11998 NIAAA NIH HHS United States
AA13320 NIAAA NIH HHS United States
AA13321 NIAAA NIH HHS United States
AA14041 NIAAA NIH HHS United States
AA17688 NIAAA NIH HHS United States
DA012854 NIDA NIH HHS United States
DA019951 NIDA NIH HHS United States
K05 AA017688 NIAAA NIH HHS United States
K05 AA017688-03 NIAAA NIH HHS United States
K08 DA019951 NIDA NIH HHS United States
K08 DA019951-05 NIDA NIH HHS United States
P60 AA011998 NIAAA NIH HHS United States
P60 AA011998-12 NIAAA NIH HHS United States
R01 AA007535 NIAAA NIH HHS United States
R01 AA007535-08 NIAAA NIH HHS United States
R01 AA013320 NIAAA NIH HHS United States
R01 AA013320-04 NIAAA NIH HHS United States
R01 AA013320-05 NIAAA NIH HHS United States
R01 AA013321 NIAAA NIH HHS United States
R01 AA013321-05 NIAAA NIH HHS United States
R01 AA014041-05 NIAAA NIH HHS United States
R01 DA012854 NIDA NIH HHS United States
R01 DA012854-08 NIDA NIH HHS United States
R37 AA007728 NIAAA NIH HHS United States
R37 AA007728-20 NIAAA NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Alcohol Drinking genetics
Alcoholism genetics
Case-Control Studies genetics
Genetic Predisposition to Disease genetics
Genome-Wide Association Study statistics & numerical data
Genotype statistics & numerical data
Humans statistics & numerical data
Phenotype statistics & numerical data
Polymorphism, Single Nucleotide statistics & numerical data
Quantitative Trait Loci genetics
Residence Characteristics genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
NIHMS283454 NLM
PMC3210694 NLM