Journal article
A genome wide association study of alcohol dependence symptom counts in extended pedigrees identifies C15orf53
Molecular psychiatry, Vol.18(11), pp.1218-1224
10/23/2012
DOI: 10.1038/mp.2012.143
PMCID: PMC3752321
PMID: 23089632
Abstract
Several studies have identified genes associated with alcohol use disorders, 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 (COGA) to identify novel genes affecting risk for alcohol dependence. 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). Secondary analyses were performed to determine if the single nucleotide polymorphisms (SNPs) associated with symptom count were also associated with the dichotomous phenotype, DSM-IV alcohol dependence. This family-based GWAS identified SNPs in
C15orf53
that are strongly associated with DSM-IV alcohol (
p
=4.5×10
−8
, inflation corrected
p
=9.4×10
−7
). Results with DSM-IV alcohol dependence in the regions of interest support our findings with symptom count, though the associations were less significant. Attempted replications of the most promising association results were conducted in two independent samples: non-overlapping subjects from the Study of Addiction: Genes and Environment (SAGE) and the Australian twin-family study of alcohol use disorders (OZALC). Nominal association of
C15orf53
with symptom count was observed in SAGE. The variant that showed strongest association with symptom count, rs12912251 and its highly correlated variants (D′=1, r
2
≥ 0.95), has previously been associated with risk for bipolar disorder.
Details
- Title: Subtitle
- A genome wide association study of alcohol dependence symptom counts in extended pedigrees identifies C15orf53
- Creators
- Jen-Chyong Wang - Washington University in St. LouisTatiana Foroud - Indiana UniversityAnthony L Hinrichs - Washington University in St. LouisNhung XH Le - Washington University in St. LouisSarah Bertelsen - Washington University in St. LouisJohn P Budde - Washington University in St. LouisOscar Harari - Washington University in St. LouisDaniel L Koller - Indiana UniversityLeah Wetherill - Indiana UniversityArpana Agrawal - Washington University in St. LouisLaura Almasy - Texas Biomedical Research InstituteAndrew I Brooks - Rutgers, The State University of New JerseyKathleen Bucholz - Washington University in St. LouisDanielle Dick - Virginia Commonwealth UniversityVictor Hesselbrock - University of ConnecticutEric O Johnson - RTI InternationalSun Kang - SUNY Downstate Health Sciences UniversityManav Kapoor - Washington University in St. LouisJohn Kramer - University of IowaSamuel Kuperman - University of IowaPamela AF Madden - Washington University in St. LouisNiklas Manz - SUNY Downstate Health Sciences UniversityNicholas G Martin - QIMR Berghofer Medical Research InstituteJeanette N McClintick - Indiana UniversityGrant W Montgomery - QIMR Berghofer Medical Research InstituteJohn I Nurnberger - Indiana UniversityMadhavi Rangaswamy - SUNY Downstate Health Sciences UniversityJohn Rice - Washington University in St. LouisMarc Schuckit - University of California San DiegoJay A Tischfield - Texas Biomedical Research InstituteJohn B Whitfield - QIMR Berghofer Medical Research InstituteXiaoling Xuei - Indiana UniversityBernice Porjesz - SUNY Downstate Health Sciences UniversityAndrew C Heath - Washington University in St. LouisHoward J Edenberg - Indiana UniversityLaura J Bierut - Washington University in St. LouisAlison M Goate - Washington University in St. Louis
- Resource Type
- Journal article
- Publication Details
- Molecular psychiatry, Vol.18(11), pp.1218-1224
- DOI
- 10.1038/mp.2012.143
- PMID
- 23089632
- PMCID
- PMC3752321
- NLM abbreviation
- Mol Psychiatry
- ISSN
- 1359-4184
- eISSN
- 1476-5578
- Grant note
- U10 AA008401 || AA / National Institute on Alcohol Abuse and Alcoholism : NIAAA
- Language
- English
- Date published
- 10/23/2012
- Academic Unit
- Psychiatry
- Record Identifier
- 9984293755602771
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