A genome-wide association study of alcohol-dependence symptom counts in extended pedigrees identifies C15orf53

被引：63

作者：

Wang, J-C ^{[1
]}

Foroud, T. ^{[2
]}

Hinrichs, A. L. ^{[1
]}

Le, N. X. H. ^{[1
]}

Bertelsen, S. ^{[1
]}

Budde, J. P. ^{[1
]}

Harari, O.

Koller, D. L. ^{[2
]}

Wetherill, L. ^{[2
]}

Agrawal, A. ^{[1
]}

Almasy, L. ^{[3
]}

Brooks, A. I. ^{[4
]}

Bucholz, K. ^{[1
]}

Dick, D. ^{[5
]}

Hesselbrock, V. ^{[6
]}

Johnson, E. O. ^{[7
]}

Kang, S. ^{[8
]}

Kapoor, M. ^{[1
]}

Kramer, J. ^{[9
]}

Kuperman, S. ^{[10
]}

Madden, P. A. F. ^{[1
]}

Manz, N. ^{[8
]}

Martin, N. G. ^{[11
]}

McClintick, J. N. ^{[12
]}

Montgomery, G. W. ^{[11
]}

Nurnberger, J. I., Jr. ^{[13
]}

Rangaswamy, M. ^{[8
]}

Rice, J. ^{[1
]}

Schuckit, M. ^{[14
]}

Tischfield, J. A. ^{[3
]}

Whitfield, J. B. ^{[11
]}

Xuei, X. ^{[12
]}

Porjesz, B.

Heath, A. C. ^{[1
]}

Edenberg, H. J. ^{[2
,12
]}

Bierut, L. J. ^{[1
]}

Goate, A. M. ^{[1
]}

机构：

[1] Washington Univ, Dept Psychiat, Sch Med, St Louis, MO 63110 USA

[2] Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA

[3] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA

[4] Rutgers State Univ, Dept Genet, Piscataway, NJ USA

[5] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA

[6] Univ Connecticut, Ctr Hlth, Dept Psychiat, Farmington, CT 06032 USA

[7] Res Triangle Inst Int, Div Hlth Social & Econ Res, Res Triangle Pk, NC USA

[8] Suny Downstate Med Ctr, Dept Psychiat & Behav Sci, Henri Begleiter Neurodynam Lab, Brooklyn, NY 11203 USA

[9] Univ Iowa, Coll Med, Dept Psychiat, Iowa City, IA 52242 USA

[10] Univ Iowa Hosp, Div Child Psychiat, Iowa City, IA USA

[11] Queensland Inst Med Res, Brisbane, Qld 4006, Australia

[12] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN USA

[13] Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA

[14] Univ Calif San Diego, San Diego Dept Psychiat, La Jolla, CA USA

来源：

MOLECULAR PSYCHIATRY | 2013年 / 18卷 / 11期

关键词：

C15orf53; DSM-IV alcohol-dependence symptoms; family-based GWAS; quantitative traits; ENVIRONMENTAL CONTRIBUTIONS; GENERAL-POPULATION; GENETIC INFLUENCES; BIPOLAR DISORDER; FAMILY; SAMPLE; RISK; COMORBIDITY; RELATIVES; PATTERNS;

D O I：

10.1038/mp.2012.143

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 x 10(-8), inflation-corrected P = 9.4 x 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.

引用

页码：1218 / 1224

页数：7

共 48 条

[1]

[Anonymous], 2010, GLOB STRAT RED HARMF

[2]

[Anonymous], 2006, QUANTO 1 2 COMPUTER

[3] Inattentiveness, parental smoking and adolescent smoking initiation [J].

Barman, SK ;

Pulkkinen, L ;

Kaprio, J ;

Rose, RJ .

ADDICTION, 2004, 99 (08) :1049-1061

[4] EVENT-RELATED BRAIN POTENTIALS DIFFERENTIATE PRIMING AND RECOGNITION TO FAMILIAR AND UNFAMILIAR FACES [J].

BEGLEITER, H ;

PORJESZ, B ;

WANG, WY .

ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY, 1995, 94 (01) :41-49

[5] A genome-wide association study of alcohol dependence [J].

Bierut, Laura J. ;

Agrawal, Arpana ;

Bucholz, Kathleen K. ;

Doheny, Kimberly F. ;

Laurie, Cathy ;

Pugh, Elizabeth ;

Fisher, Sherri ;

Fox, Louis ;

Howells, William ;

Bertelsen, Sarah ;

Hinrichs, Anthony L. ;

Almasy, Laura ;

Breslau, Naomi ;

Culverhouse, Robert C. ;

Dick, Danielle M. ;

Edenberg, Howard J. ;

Foroud, Tatiana ;

Grucza, Richard A. ;

Hatsukami, Dorothy ;

Hesselbrock, Victor ;

Johnson, Eric O. ;

Kramer, John ;

Krueger, Robert F. ;

Kuperman, Samuel ;

Lynskey, Michael ;

Mann, Karl ;

Neuman, Rosalind J. ;

Noethen, Markus M. ;

Nurnberger, John I., Jr. ;

Porjesz, Bernice ;

Ridinger, Monika ;

Saccone, Nancy L. ;

Saccone, Scott F. ;

Schuckit, Marc A. ;

Tischfield, Jay A. ;

Wang, Jen C. ;

Rietschel, Marcella ;

Goate, Alison M. ;

Rice, John P. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (11) :5082-5087

[6] A Unified Approach to Genotype Imputation and Haplotype-Phase Inference for Large Data Sets of Trios and Unrelated Individuals [J].

Browning, Brian L. ;

Browning, Sharon R. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2009, 84 (02) :210-223

[7] Can we subtype alcoholism? A latent class analysis of data from relatives of alcoholics in a multicenter family study of alcoholism [J].

Bucholz, KK ;

Heath, AC ;

Reich, T ;

Hesselbrock, VM ;

Kramer, JR ;

Nurnberger, JI ;

Schuckit, MA .

ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 1996, 20 (08) :1462-1471

[8] GWAF: an R package for genome-wide association analyses with family data [J].

Chen, Ming-Huei ;

Yang, Qiong .

BIOINFORMATICS, 2010, 26 (04) :580-581

[9] Genomic control for association studies [J].

Devlin, B ;

Roeder, K .

BIOMETRICS, 1999, 55 (04) :997-1004

[10] Role of GABRA2 in Trajectories of Externalizing Behavior Across Development and Evidence of Moderation by Parental Monitoring [J].

Dick, Danielle M. ;

Latendresse, Shawn J. ;

Lansford, Jennifer E. ;

Budde, John P. ;

Goate, Alison ;

Dodge, Kenneth A. ;

Pettit, Gregory S. ;

Bates, John E. .

ARCHIVES OF GENERAL PSYCHIATRY, 2009, 66 (06) :649-657

← 1 2 3 4 5 →