Addiction_conference_James_MacKillop

Addiction_conference_James_MacKillop - Genetic Influences...

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Unformatted text preview: Genetic Influences on Addiction: Empirical Evidence, Functional Mechanisms, and Clinical Implications James MacKillop, PhD Center for Alcohol and Addiction Studies, Brown University John E. McGeary, PhD Providence VMAC Center for Alcohol and Addiction Studies, Brown University Overview Evidence of Genetic Influences Recent Research on Potential Genetic Mechanisms Implications of Genetic Influences I. Empirical Evidence of Genetic Influences Genetic Epidemiology Genetic Linkage Analysis Candidate Gene Studies Animal Models I. Empirical Evidence of Genetic Influences Genetic Epidemiology Genetic Linkage Analysis Candidate Gene Studies Animal Models Alcoholism in Adopted Children of Alcoholic and Nonalcoholic Biological Parents Alcoholism Hx Study +- Odds-Ratio Males Goodwin et al. (1973) 18% 5% 4.11* Cloninger et al. (1981) 23% 15% 1.73* Cadoret et al. (1985) 61% 24% 5.02* Cadoret et al. (1987) 63% 20% 6.51* Sigvardsson et al. (1996) 24% 13% 2.20* Females Goodwin et al. (1973) 2% 4% 0.49 Bohman et al. (1981) 5% 3% 1.73* Cadoret et al. (1985) 33% 5% 8.88* Sigvardsson et al. (1996) 1% 1% 0.80 Table from McGue (1999a) * p < .05 I. Empirical Evidence of Genetic Influences Genetic Epidemiology Genetic Linkage Analysis Candidate Gene Studies Animal Models Prevalence of Alcoholism in Monozygotic and Dizygotic Twins Data from Kendler et al. (1997); table from McGue (1999b) Total n = 17,780 I. Empirical Evidence of Genetic Influences Genetic Epidemiology Genetic Linkage Analysis Candidate Gene Studies Animal Models Genetic Linkage Analysis: COGA Collaborative Study on the Genetics of Alcoholism Proband + > two siblings with alcoholism Sample = 262 families, n = 2282 Multiple highly significant overlapping portions of the genome Foroud et al. (2000) I. Empirical Evidence of Genetic Influences Genetic Epidemiology Genetic Linkage Analysis Candidate Gene Studies Animal Models Candidate Genes Metabolic: ALDH2 CYP1A6 CNS Neurotransmission: GABRA2 DRD2 TaqIA DRD4 VNTR SLC6A3 OPRM1 I. Empirical Evidence of Genetic Influences Genetic Epidemiology Genetic Linkage Analysis Candidate Gene Studies Animal Models Plomin (2001); adapted from Tryon (1940) Maze Bright vs. Maze Dull Rodents C57BL/6 DBA/2J Alcohol Preferring and Abstaining Mice Crabbe (2005) High Alcohol Preference Low Alcohol Preference Alcohol Consumption by Mouse Strain Crabbe (2005) I. Empirical Evidence of Genetic Influences Genetic Epidemiology Genetic Linkage Analysis Candidate Gene Studies Animal Models Overall Variance of Risk Environment 40% Genetics 60% (Heterogeneous and Polygenic) Schuckit & Crabbe (2000) II. Functional Mechanisms Underlying Genetic Influences One does not inherit risk: One inherits specific risk-promoting or risk-protective genes. Crabbe (2003) II. Functional Mechanisms Underlying Genetic Influences One does not inherit risk:...
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Addiction_conference_James_MacKillop - Genetic Influences...

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