Genetics of alcohol dependence

被引:88
作者
Gelernter, Joel [1 ,2 ,3 ,4 ]
Kranzler, Henry R. [5 ]
机构
[1] Yale Univ, Sch Med, VAMC 116A2, Dept Psychiat, West Haven, CT 06516 USA
[2] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA
[3] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT USA
[4] VA Connecticut Healthcare Syst, West Haven, CT USA
[5] Univ Connecticut, Sch Med, Dept Psychiat, Farmington, CT USA
关键词
OPIOID RECEPTOR GENE; SEROTONIN TRANSPORTER GENE; GENOME-WIDE ASSOCIATION; POPULATION-BASED SAMPLE; STRESSFUL LIFE EVENTS; LINKAGE DISEQUILIBRIUM; LUNG-CANCER; SUBSTANCE DEPENDENCE; SUSCEPTIBILITY LOCUS; NALTREXONE TREATMENT;
D O I
10.1007/s00439-009-0701-2
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Alcohol dependence (AD), a genetically influenced phenotype, is extremely costly to individuals and to society in the United States and throughout the world, contributing to morbidity and mortality and a host of economic, interpersonal, and societal problems. Although until recently the only genes established to affect risk for AD were those encoding several alcohol metabolizing enzymes, there are now several other genes that can be regarded as confirmed risk loci, discovered through linkage and candidate gene association studies. While the mechanism of action of the effects of alcohol-metabolizing enzymes on AD risk is thought to be well understood, we are still in the early stages of understanding the physiology of other risk loci. Further, it is clear that only a small number of the many genes that influence risk for AD have been identified. Newer methodologies (e.g., genomewide association, study of copy number variation, and deep sequencing of candidate loci to identify rare risk variants) that have improved our understanding of other complex traits hold the promise of identifying a greater set of AD susceptibility loci.
引用
收藏
页码:91 / 99
页数:9
相关论文
共 81 条
[1]   Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1 [J].
Amos, Christopher I. ;
Wu, Xifeng ;
Broderick, Peter ;
Gorlov, Ivan P. ;
Gu, Jian ;
Eisen, Timothy ;
Dong, Qiong ;
Zhang, Qing ;
Gu, Xiangjun ;
Vijayakrishnan, Jayaram ;
Sullivan, Kate ;
Matakidou, Athena ;
Wang, Yufei ;
Mills, Gordon ;
Doheny, Kimberly ;
Tsai, Ya-Yu ;
Chen, Wei Vivien ;
Shete, Sanjay ;
Spitz, Margaret R. ;
Houlston, Richard S. .
NATURE GENETICS, 2008, 40 (05) :616-622
[2]   An evaluation of μ-opioid receptor (OPRM1) as a predictor of naltrexone response in the treatment of alcohol dependence [J].
Anton, Raymond F. ;
Oroszi, Gabor ;
O'Malley, Stephanie ;
Couper, David ;
Swift, Robert ;
Pettinati, Helen ;
Goldman, David .
ARCHIVES OF GENERAL PSYCHIATRY, 2008, 65 (02) :135-144
[3]   Combined pharmacotherapies and behavioral interventions for alcohol dependence - The COMBINE study: A randomized controlled trial [J].
Anton, RF ;
O'Malley, SS ;
Ciraulo, DA ;
Cisler, RA ;
Couper, D ;
Donovan, DM ;
Gastfriend, DR ;
Hosking, JD ;
Johnson, BA ;
LoCastro, JS ;
Longabaugh, R ;
Mason, BJ ;
Mattson, ME ;
Miller, WR ;
Pettinati, HM ;
Randall, CL ;
Swift, R ;
Weiss, RD ;
Williams, LD ;
Zweben, A .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2006, 295 (17) :2003-2017
[4]   Association of an Asn40Asp (A118G) polymorphism in the μ-opioid receptor gene with substance dependence:: A meta-analysis [J].
Arias, Albert ;
Feinn, Richard ;
Kranzler, Henry R. .
DRUG AND ALCOHOL DEPENDENCE, 2006, 83 (03) :262-268
[5]   Variation in GABRA2 predicts drinking behavior in project MATCH subjects [J].
Bauer, Lance O. ;
Covault, Jonathan ;
Harel, Ofer ;
Das, Sourish ;
Gelernter, Joel ;
Anton, Raymond ;
Kranzler, Henry R. .
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 2007, 31 (11) :1780-1787
[6]   α-5/α-3 nicotinic receptor subunit alleles increase risk for heavy smoking [J].
Berrettine, W. ;
Yuan, X. ;
Tozzi, F. ;
Song, K. ;
Francks, C. ;
Chilcoat, H. ;
Waterworth, D. ;
Muglia, P. ;
Mooser, V. .
MOLECULAR PSYCHIATRY, 2008, 13 (04) :368-373
[7]   Novel genes identified in a high-density genome wide association study for nicotine dependence [J].
Bierut, Laura Jean ;
Madden, Pamela A. F. ;
Breslau, Naomi ;
Johnson, Eric O. ;
Hatsukami, Dorothy ;
Pomerleau, Ovide F. ;
Swan, Gary E. ;
Rutter, Joni ;
Bertelsen, Sarah ;
Fox, Louis ;
Fugman, Douglas ;
Goate, Alison M. ;
Hinrichs, Anthony L. ;
Konvicka, Karel ;
Martin, Nicholas G. ;
Montgomery, Grant W. ;
Saccone, Nancy L. ;
Saccone, Scott F. ;
Wang, Jen C. ;
Chase, Gary A. ;
Rice, John P. ;
Ballinger, Dennis G. .
HUMAN MOLECULAR GENETICS, 2007, 16 (01) :24-35
[8]   Interaction between CRHR1 gene and stressful life events predicts adolescent heavy alcohol use [J].
Blomeyer, Dorothea ;
Treutlein, Jens ;
Esser, Guenter ;
Schmidt, Martin H. ;
Schumann, Gunter ;
Laucht, Manfred .
BIOLOGICAL PSYCHIATRY, 2008, 63 (02) :146-151
[9]   Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene [J].
Caspi, A ;
Sugden, K ;
Moffitt, TE ;
Taylor, A ;
Craig, IW ;
Harrington, H ;
McClay, J ;
Mill, J ;
Martin, J ;
Braithwaite, A ;
Poulton, R .
SCIENCE, 2003, 301 (5631) :386-389
[10]   Opinion - Gene-environment interactions in psychiatry: joining forces with neuroscience [J].
Caspi, Avshalom ;
Moffitt, Terrie E. .
NATURE REVIEWS NEUROSCIENCE, 2006, 7 (07) :583-590