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
23089632
TITLE
A genome-wide association study of alcohol-dependence symptom counts in extended pedigrees identifies C15orf53.
ABSTRACT
Several studies have identified genes associated with alcohol-use disorders (AUDs), but the variation in each of these genes explains only a small portion of the genetic vulnerability. The goal of the present study was to perform a genome-wide association study (GWAS) in extended families from the Collaborative Study on the Genetics of Alcoholism to identify novel genes affecting risk for alcohol dependence (AD). To maximize the power of the extended family design, we used a quantitative endophenotype, measured in all individuals: number of alcohol-dependence symptoms endorsed (symptom count (SC)). Secondary analyses were performed to determine if the single nucleotide polymorphisms (SNPs) associated with SC were also associated with the dichotomous phenotype, DSM-IV AD. This family-based GWAS identified SNPs in C15orf53 that are strongly associated with DSM-IV alcohol-dependence symptom counts (P=4.5 × 10(-8), inflation-corrected P=9.4 × 10(-7)). Results with DSM-IV AD in the regions of interest support our findings with SC, although the associations were less significant. Attempted replications of the most promising association results were conducted in two independent samples: nonoverlapping subjects from the Study of Addiction: Genes and Environment (SAGE) and the Australian Twin Family Study of AUDs (OZALC). Nominal association of C15orf53 with SC was observed in SAGE. The variant that showed strongest association with SC, rs12912251 and its highly correlated variants (D'=1, r(2) 0.95), have previously been associated with risk for bipolar disorder.
DATE PUBLISHED
2013 Nov
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2011/12/29
revised 2012/07/26
accepted 2012/09/04
aheadofprint 2012/10/23
entrez 2012/10/24 06:00
pubmed 2012/10/24 06:00
medline 2014/10/28 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Wang JC Wang J-C JC Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA.
Foroud T Foroud T T
Hinrichs AL Hinrichs A L AL
Le NX Le N X H NX
Bertelsen S Bertelsen S S
Budde JP Budde J P JP
Harari O Harari O O
Koller DL Koller D L DL
Wetherill L Wetherill L L
Agrawal A Agrawal A A
Almasy L Almasy L L
Brooks AI Brooks A I AI
Bucholz K Bucholz K K
Dick D Dick D D
Hesselbrock V Hesselbrock V V
Johnson EO Johnson E O EO
Kang S Kang S S
Kapoor M Kapoor M M
Kramer J Kramer J J
Kuperman S Kuperman S S
Madden PA Madden P A F PA
Manz N Manz N N
Martin NG Martin N G NG
McClintick JN McClintick J N JN
Montgomery GW Montgomery G W GW
Nurnberger JI Jr Nurnberger J I JI
Rangaswamy M Rangaswamy M M
Rice J Rice J J
Schuckit M Schuckit M M
Tischfield JA Tischfield J A JA
Whitfield JB Whitfield J B JB
Xuei X Xuei X X
Porjesz B Porjesz B B
Heath AC Heath A C AC
Edenberg HJ Edenberg H J HJ
Bierut LJ Bierut L J LJ
Goate AM Goate A M AM
INVESTIGATORS
JOURNAL
VOLUME: 18
ISSUE: 11
TITLE: Molecular psychiatry
ISOABBREVIATION: Mol. Psychiatry
YEAR: 2013
MONTH: Nov
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1476-5578
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Mol Psychiatry
COUNTRY: England
ISSNLINKING: 1359-4184
NLMUNIQUEID: 9607835
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Twin Study
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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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
P01 CA089392 NCI NIH HHS United States
R01 DA013423 NIDA NIH HHS United States
R01 DA019963 NIDA NIH HHS United States
R25 DA027995 NIDA NIH HHS United States
R28 AA012725 NIAAA NIH HHS United States
U01 HG004446 NHGRI NIH HHS United States
U01HG004422 NHGRI NIH HHS United States
U01HG004438 NHGRI NIH HHS United States
U10 AA008401 NIAAA NIH HHS United States
U10 AA008401 NIAAA NIH HHS United States
U10AA008401 NIAAA NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Alcoholism genetics
Chromosomes, Human, Pair 15 genetics
Diagnostic and Statistical Manual of Mental Disorders genetics
Endophenotypes genetics
Female genetics
Genetic Predisposition to Disease genetics
Genome-Wide Association Study genetics
Genotype genetics
Humans genetics
Male genetics
Open Reading Frames genetics
Pedigree genetics
Polymorphism, Single Nucleotide genetics
Symptom Assessment genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
NIHMS466495 NLM
PMC3752321 NLM