Skip to main content Accessibility help
×
Home
  • Print publication year: 2012
  • Online publication date: September 2012

2 - The implications of genetic research on alcohol dependence for prevention and treatment

from Section 1 - Introduction

Summary

Introduction

Alcohol dependence is a disorder that causes significant harm, not only to the health of affected individuals, but also through the significant social and economic costs borne by society. About 4% of the global burden of disease (measured by disability-adjusted life years; DALY) has been attributed to alcohol consumption and 1.6% to alcohol-use disorders specifically (WHO, 2008). In high-income countries such as the United States, alcohol-use disorders cause 3.4% of total disease burden (WHO, 2008).

Alcohol dependence (AD) may manifest in tolerance, withdrawal symptoms, or the use of alcohol to avoid or relieve withdrawal, drinking more than intended, unsuccessful attempts to cut down use, excessive time related to alcohol consumption (including alcohol seeking), impaired social or work activities, and continued use despite physical or psychological consequences. AD may increase a person’s risk of other forms of substance abuse, psychiatric disorders, and physical illnesses, such as heart disease and cancers, and lead to unemployment, relationship breakdowns, accidents, and imprisonment due to crimes committed as a result of alcohol abuse.

The existence of a genetic component of AD has long been suggested by the observation that the disorder runs in families. The substantial genetic contribution has subsequently been confirmed by twin and adoption studies that estimate the heritability of AD to range from 50 to 60% (Agrawal and Lynskey, 2008 ). Approximately 56% of the variance in AD is caused by genetic factors, whereas 44% is as a result of specific environmental factors not shared by family members, including peer influences and experiences after leaving the home environment (Kendler and Prescott, 2006 ). Shared environmental factors such as social class, parental rearing styles, familial attitudes to drinking, parental drinking practices, and – in the case of twins – intrauterine environment, make little contribution to AD itself (Kendler and Prescott, 2006 ) but explain about 15% of the variance in initiation of alcohol use (Sartor et al., 2009 ).

Related content

Powered by UNSILO
References
Agrawal, A.Lynskey, M. T. 2008 Are there genetic influences on addiction: evidence from family, adoption and twin studiesAddiction 103 1069
Anton, R. F.O’Malley, S. S.Ciraulo, D. A. 2006 Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trialJAMA 295 2003
Anton, R. F.Oroszi, G.O’Malley, S. 2008 An evaluation of mu-opioid receptor (OPRM1) as a predictor of naltrexone response in the treatment of alcohol dependence: results from the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) studyArchives of General Psychiatry 65 135
Ball, D. 2008 Addiction science and its geneticsAddiction 103 360
Bond, C.Laforge, K. S.Tian, M. 1998 Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity: possible implications for opiate addictionProceedings of the National Academy of Sciences USA 95 9608
Bosron, W. F.Magnes, L. J.Li, T. K. 1983 Kinetic and electrophoretic properties of native and recombined isoenzymes of human liver alcohol dehydrogenaseBiochemistry 22 1852
Buckland, P. R. 2001 Genetic association studies of alcoholism: problems with the candidate gene approachAlcohol and Alcoholism 36 99
Chen, C. C.Lu, R. B.Chen, Y. C. 1999 Interaction between the functional polymorphisms of the alcohol-metabolism genes in protection against alcoholismAmerican Journal of Human Genetics 65 795
Choi, I. G.Son, H. G.Yang, B. H. 2005 Scanning of genetic effects of alcohol metabolism gene ( and ) polymorphisms on the risk of alcoholismHuman Mutation 26 224
Clarke, T. K.Schumann, G. 2009 Gene-environment interactions resulting in risky alcohol drinking behaviour are mediated by CRF and CRF1Pharmacology, Biochemistry and Behavior 93 230
Collins, F. S.Green, E. D.Guttmacher, A. E.Guyer, M. S. 2003 A vision for the future of genomics researchNature 422 835
Conrod, P. J.Peterson, J. B.Pihl, R. O.Mankowski, S. 1997 Biphasic effects of alcohol on heart rate are influenced by alcoholic family history and rate of alcohol ingestionAlcoholism, Clinical and Experimental Research 21 140
Covault, J.Tennen, H.Armell, S. 2007 Interactive effects of the serotonin transporter 5-HTTLPR polymorphism and stressful life events on college student drinking and drug useBiological Psychiatry 61 609
Covault, J.Gelerenter, J.Jensen, K.Anton, R.Kranzler, H. R. 2008 Markers in the 5′-region of associate to alcohol dependence and are in linkage disequilibrium with markers in the adjacent geneNeuropsychopharmacology 33 837
Crabb, D. W.Matsumoto, M.Chang, D.You, M. 2004 Overview of the role of alcohol dehydrogenase and aldehyde dehydrogenase and their variants in the genesis of alcohol-related pathologyThe Proceedings of the Nutrition Society 63 49
Ducci, F.Enoch, M. A.Hodgkinson, C. 2008 Interaction between a functional MAOA locus and childhood sexual abuse predicts alcoholism and antisocial personality disorder in adult womenMolecular Psychiatry 13 334
Edenberg, H. J. 2002 The collaborative study on the genetics of alcoholism: an updateAlcohol Research and Health 26 214
Edenberg, H. J. 2007 The genetics of alcohol metabolism: role of alcohol dehydrogenase and aldehyde dehydrogenase variantsAlcohol Research and Health 30 5
Edenberg, H. J.Foroud, T. 2006 The genetics of alcoholism: identifying specific genes through family studiesAddiction Biology 11 386
Ehlers, C. L.Gilder, D. A.Wall, T. L. 2004 Genomic screen for loci associated with alcohol dependence in Mission IndiansAmerican Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 129B 110
Ehlers, C. L.Spence, J. P.Wall, T. L.Gilder, D. A.Carr, L. G. 2004 Association of ALDH1 promoter polymorphisms with alcohol-related phenotypes in southwest California IndiansAlcoholism, Clinical and Experimental Research 28 1481
Eng, M. Y.Luczak, S. E.Wall, T. L. 2007 , , and genotypes in Asians: a literature reviewAlcohol Research and Health 30 22
Enoch, M. A.Hodgkinson, C. A.Yuan, Q. 2009 and as independent predictors for alcoholism in two populationsNeuropsychopharmacology 34 1245
Faraone, S. V. 1999 Genetics of Mental DisordersNew YorkGuilford Press
Feinn, R.Nellissery, M.Kranzler, H. R. 2005 Meta-analysis of the association of a functional serotonin transporter promoter polymorphism with alcohol dependenceAmerican Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 133B 79
Feldstein Ewing, S. W.Lachance, H. A.Bryan, A.Hutchison, K. E. 2009 Do genetic and individual risk factors moderate the efficacy of motivational enhancement therapy? Drinking outcomes with an emerging adult sampleAddiction Biology 14 356
Flint, J.Munafò, M. R. 2008 Forum: Interactions between gene and environmentCurrent Opinion in Psychiatry 21 315
Flowers, C. R.Veenstra, D. 2004 The role of cost-effectiveness analysis in the era of pharmacogenomicsPharmacoeconomics 22 481
Gartner, C. E.Barendregt, J. J.Hall, W. D. 2009 Multiple genetic tests for susceptibility to smoking do not outperform simple family historyAddiction 104 118
Gelernter, J.Kranzler, H. R. 2009 Genetics of alcohol dependenceHuman Genetics 126 91
Gelernter, J.Gueorguieva, R.Kranzler, H. R. 2007 Opioid receptor gene (, , and ) variants and response to naltrexone treatment for alcohol dependence: results from the VA Cooperative StudyAlcoholism, Clinical and Experimental Research 31 555
Gianoulakis, C. 2001 Influence of the endogenous opioid system on high alcohol consumption and genetic predisposition to alcoholismJournal of Psychiatry and Neuroscience 26 304
Guindalini, C.Scivoletto, S.Ferreira, R. G. M. 2005 Association of genetic variants in alcohol dehydrogenase 4 with alcohol dependence in Brazilian patientsAmerican Journal of Psychiatry 162 1005
Hall, W. 2004 Feeling ‘better than well’EMBO Reports 5 1105
Hall, W. D.Gartner, C. E.Carter, A. 2008 The genetics of nicotine addiction liability: ethical and social policy implicationsAddiction 103 350
Hasin, D.Aharonovich, E.Liu, X. 2002 Alcohol and in Israel: Ashkenazis, Sephardics, and recent Russian immigrantsAmerican Journal of Psychiatry 159 1432
Heilig, M.Thorsell, A.Sommer, W. H. 2010 Translating the neuroscience of alcoholism into clinical treatments: from blocking the buzz to curing the bluesNeuroscience and Biobehavioral Reviews 35 334
Heinz, A.Goldman, D.Gallinat, J.Schumann, G.Puls, I. 2004 Pharmacogenetic insights to monoaminergic dysfunction in alcohol dependencePsychopharmacology 174 561
Heinz, A.Beck, A.Wrase, J. 2009 Neurotransmitter systems in alcohol dependencePharmacopsychiatry 42 S95
Holtzman, N. A.Marteau, T. M. 2000 Will genetics revolutionize medicine?New England Journal of Medicine 343 141
Huang, C. L. C. 2010 The role of serotonin and possible interaction of serotonin-related genes with alcohol dehydrogenase and aldehyde dehydrogenase genes in alcohol dependence: a reviewAmerican Journal of Translational Research 2 190
Janssens, A. C. J. W.Aulchenko, Y. S.Elefante, S. 2006 Predictive testing for complex diseases using multiple genes: fact or fiction?Genetics in Medicine 8 395
Kalsi, G.Prescott, C. A.Kendler, K. S.Riley, B. P. 2009 Unraveling the molecular mechanisms of alcohol dependenceTrends in Genetics 25 49
Kaminen-Ahola, N.Ahola, A.Maga, M. 2010 Maternal ethanol consumption alters the epigenotype and the phenotype of offspring in a mouse modelPLoS Genetics 6 e1000811
Kendler, K. S.Prescott, C. A. 2006 Genes, Environment and PsychopathologyNew YorkGuilford Press
Khoury, M. J.Yang, Q.Gwinn, M.Little, J.Dana, F. W. 2004 An epidemiologic assessment of genomic profiling for measuring susceptibility to common diseases and targeting interventionsGenetics in Medicine 6 38
Kim, S. G.Kim, C. M.Kang, D. H. 2004 Association of functional opioid receptor genotypes with alcohol dependence in KoreansAlcoholism, Clinical and Experimental Research 28 986
Kohnke, M. D. 2008 Approach to the genetics of alcoholism: a review based on pathophysiologyBiochemical Pharmacology 75 160
Kohnke, M. D.Kolb, W.Lutz, U.Maurer, S.Batra, A. 2006 The serotonin transporter promotor polymorphism is not associated with alcoholism or severe forms of alcohol withdrawal in a German samplePsychiatric Genetics 16 227
Koob, G. F.Le Moal, M. 2006 Neurobiology of AddictionNew York:Academic Press
Kraft, P.Hunter, D. J. 2009 Genetic risk prediction – are we there yet?New England Journal of Medicine 360 1701
Kuehn, B. M. 2009 Findings on alcohol dependence point to promising avenues for targeted therapiesThe Journal of the American Medical Association 301 1643
Le Foll, B.Gallo, A.Le Strat, Y.Lu, L.Gorwood, P. 2009 Genetics of dopamine receptors and drug addiction: a comprehensive reviewBehavioural Pharmacology 20 1
Lee, S. Y.Hahan, C.Y.Lee, J. F. 2010 MAOA interacts with the gene in anxiety-depression alcohol dependenceAlcoholism, Clinical and Experimental Research 34 1212
Lerman, C.Wileyto, E. P.Patterson, F. 2004 The functional mu opioid receptor () variant predicts short-term response to nicotine replacement therapy in a clinical trialPharmacogenomics Journal 4 184
Luczak, S. E.Shea, S. H.Carr, L. G.Li, T. K.Wall, T. L. 2002 Binge drinking in Jewish and non-Jewish white college studentsAlcoholism, Clinical and Experimental Research 26 1773
Luczak, S. E.Glatt, S. J.Wall, T. L. 2006 Meta-analyses of and with alcohol dependence in AsiansPsychological Bulletin 132 607
Luo, X.Kranzler, H. R.Zuo, L. 2005 gene variation is associated with alcohol and drug dependence: results from family controlled and population-structured association studiesPharmacogenetics and Genomics 15 755
Luo, X.Kranzler, H. R.Zuo, L. 2006 gene variation is associated with alcohol dependence and drug dependence in European Americans: results from HWD tests and case-control association studiesNeuropsychopharmacology 31 1085
Mattes, J. A. 2009 Questionable efficacy for naltrexone in patients with Archives of General Psychiatry 66 796
McCarver, D. G.Thomasson, H. R.Martier, S. S.Sokol, R. J.Li, T. K. 1997 Alcohol dehydrogenase-2*3 allele protects against alcohol-related birth defects among African AmericansJournal of Pharmacology and Experimental Therapeutics 283 1095
McHugh, R. K.Hofmann, S. G.Asnaani, A.Sawyer, A. T.Otto, M. W. 2010 The serotonin transporter gene and risk for alcohol dependence: a meta-analytic reviewDrug and Alcohol Dependence 108 1
Miller, W. R.Walters, S. T.Bennett, M. E. 2001 How effective is alcoholism treatment in the United States?Journal of Studies on Alcohol 62 211
Munafò, M. R.Elliot, K. M.Murphy, M. F. G.Walton, R. T.Johnstone, E. C. 2007 Association of the mu-opioid receptor gene with smoking cessationPharmacogenomics Journal 7 353
Munafò, M. R.Matheson, I. J.Flint, J. 2007 Association of the gene Taq1A polymorphism and alcoholism: a meta-analysis of case-control studies and evidence of publication biasMolecular Psychiatry 12 454
Neumark, Y. D.Friedlander, Y.Thomasson, H. R.Li, T. K. 1998 Association of the allele with reduced ethanol consumption in Jewish men in Israel: a pilot studyJournal of Studies on Alcohol 59 133
Nilsson, K. W.Sjoberg, R. L.Damberg, M. 2005 Role of the serotonin transporter gene and family function in adolescent alcohol consumptionAlcoholism, Clinical and Experimental Research 29 564
Nilsson, K. W.Sjoberg, R. L.Wargelius, H. L. 2007 The monoamine oxidase A (MAO-A) gene, family function and maltreatment as predictors of destructive behaviour during male adolescent alcohol consumptionAddiction 102 389
Oota, H.Pakstis, A. J.Bonne-Tamir, B. 2004 The evolution and population genetics of the locus: random genetic drift, selection, and low levels of recombinationAnnals of Human Genetics 68 93
Ooteman, W.Naassila, M.Koeter, M. W. J. 2009 Predicting the effect of naltrexone and acamprosate in alcohol-dependent patients using genetic indicatorsAddiction Biology 14 328
Osier, M.Pakstis, A. J.Kidd, J. R. 1999 Linkage disequilibrium at the and loci and risk of alcoholismAmerican Journal of Human Genetics 64 1147
Oslin, D. W.Berettini, W.Kranzler, H. R. 2003 A functional polymorphism of the mu-opioid receptor gene is associated with naltrexone response in alcohol-dependent patientsNeuropsychopharmacology 28 1546
Pandey, S.Ugale, R.Zhang, H.Tang, L.Prakash, A. 2008 Brain chromatin remodeling: a novel mechanism of alcoholismJournal of Neuroscience 28 3729
Pharoah, P. D. P.Antoniou, A.Bobrow, M. 2002 Polygenic susceptibility to breast cancer and implications for preventionNature Genetics 31 33
Pierucci-Lagha, A.Covault, J.Feinn, R. 2005 alleles moderate the subjective effects of alcohol, which are attenuated by finasterideNeuropsychopharmacology 30 1193
Pinto, E.Reggers, J.Gorwood, P. 2008 The short allele of the serotonin transporter promoter polymorphism influences relapse in alcohol dependenceAlcohol and Alcoholism 43 398
Ray, L. A.Hutchison, K. E. 2007 Effects of naltrexone on alcohol sensitivity and genetic moderators of medication response: a double-blind placebo-controlled studyArchives of General Psychiatry 64 1069
Ray, L. A.MirandaJr., R.MacKillop, J. 2009 A preliminary pharmacogenetic investigation of adverse events from topiramate in heavy drinkersExperimental and Clinical Psychopharmacology 17 122
Ray, L. A.Mackillop, J.Monti, P. M. 2010 Subjective responses to alcohol consumption as endophenotypes: advancing behavioral genetics in etiological and treatment models of alcoholismSubstance Use and Misuse 45 1742
Renthal, W.Nestler, E. J. 2008 Epigenetic mechanisms in drug addictionTrends in Molecular Medicine 14 341
Rose, R. J.Dick, D. M. 2005 Gene-environment interplay in adolescent drinking behaviourAlcohol Research and Health 28 222
Sartor, C. E.Lynskey, M. T.Bucholz, K. K. 2009 Timing of first alcohol use and alcohol dependence: evidence of common genetic influencesAddiction 104 1512
Smith, L.Watson, M.Gates, S.Ball, D.Foxcroft, D. 2008 Meta-analysis of the association of the Taq1A polymorphism with the risk of alcohol dependency: a HuGE gene-disease association reviewAmerican Journal of Epidemiology 167 125
Soyka, M.Rosner, S. 2008 Opioid antagonists for pharmacological treatment of alcohol dependence – a critical reviewCurrent Drug Abuse Reviews 1 280
Spence, J. P.Liang, T.Eriksson, C. J. 2003 Evaluation of aldehyde dehydrogenase 1 promoter polymorphisms identified in human populationsAlcoholism, Clinical and Experimental Research 27 1389
Szeto, C. Y.Tang, N. L.Lee, D. T.Stadlin, A. 2001 Association between mu opioid receptor gene polymorphisms and Chinese heroin addictsNeuroreport 12 1103
Thomasson, H. R.Edenberg, H. J.Crabb, D. W. 1991 Alcohol and aldehyde dehydrogenase genotypes and alcoholism in Chinese menAmerican Journal of Human Genetics 48 677
Van der Zwaluw, C. S.Engels, R. C. M. E. 2009 Gene-environment interactions and alcohol use and dependence: current status and future challengesAddiction 104 907
Van der Zwaluw, C. S.Van den Wildenberg, E.Wiers, R. W. 2007 Polymorphisms in the mu-opioid receptor gene () and the implications for alcohol dependence in humansPharmacogenomics 8 1427
Viken, R. J.Rose, R. J.Morzorati, S. L.Christian, J. C.Li, T. K. 2003 Subjective intoxication in response to alcohol challenge: heritability and covariation with personality, breath alcohol level, and drinking historyAlcoholism, Clinical and Experimental Research 27 795
Viljoen, D. L.Carr, L. G.Foroud, T. M. 2001 Alcohol dehydrogenase-2*2 allele is associated with decreased prevalence of fetal alcohol syndrome in the mixed-ancestry population of the Western Cape Province, South AfricaAlcoholism, Clinical and Experimental Research 25 1719
Vineis, P.Schulte, P.McMichael, A. J. 2001 Misconceptions about the use of genetic tests in populationsLancet 357 709
Wald, N. J.Hackshaw, A. K.Frost, C. D. 1999 When can a risk factor be used as a worthwhile screening test?British Medical Journal 319 1562
Wall, T. L.Carr, L. G.Ehlers, C. L. 2003 Protective association of genetic variation in alcohol dehydrogenase with alcohol dependence in Native American Mission IndiansAmerican Journal of Psychiatry 160 41
Warren, K. R.Li, T. K. 2005 Genetic polymorphisms: impact on the risk of fetal alcohol spectrum disordersBirth Defects Research. Part A, Clinical and Molecular Teratology 73 195
Whitfield, J. B. 2002 Alcohol dehydrogenase and alcohol dependence: variation in genotype-associated risk between populationsAmerican Journal of Human Genetics 71 1247
Williams, R. 2010 Genomics in our own handsLancet Neurology 9 656
World Health Organization 2008 The Global Burden of Disease: 2004 UpdateGenevaWorld Health Organization
Zhou, Y.Proudnikov, D.Yuferov, V.Kreek, M. J. 2010 Drug-induced and genetic alterations in stress-responsive systems: Implications for specific addictive diseasesBrain Research 1314 235