Progress Toward Identification of Alcoholism Susceptibility鉴定酒精中毒易感性的研究进展.pptVIP

Progress Toward Identification of Alcoholism Susceptibility Genes on Chromosome 7 in the COGA dataset Alison M. Goate, Ph.D. Genetics of alcoholism To what extent do genetic influences impact the trait of interest? Can we identify these genetic influences? How do these genes act and interact with other genetic/environmental influences? The heritability of alcoholism Twin adoption studies Denmark, Sweden, Finland, Australia, USA Across birth cohorts late 1800s to early 1970s Across methods of assessment In-patient hospitalizations, gov’t records, diagnostics interview Across diagnostic criteria Feighner, DSMIII-R, DSMIV, ICD Heritability estimates 51-65% in females 48-73% in males COGACollaborative Study of the Genetics of Alcoholism “The long-term objective of this multi-dimensional interdisciplinary research project is to characterize the genetic factors involved in the determination of predisposition to alcoholism. This substantial undertaking involves the expertise of biochemists, clinicians, geneticists, neuropsychologists, neurophysiologists, and statisticians.” --original COGA grant application, 1989 COGA strategy COGACollaborative Study of the Genetics of Alcoholism Patients identified through inpatient/outpatient treatment programs at 6 sites General sample: 1,227 families (n=9265) Semi-structured Assessment for the Genetics of Alcoholism Interview (SSAGA) Genetic sample: 262 families (n=2282) Blood draw, EEG/ERP, neuropsychological assessments 2 waves of data collection Phenotypes used in the genetic analyses Alcohol dependence COGA= DSMIIIR plus Feighner criteria DSMIV ICD10 Other substance abuse Cocaine dependence Marijuana dependence Habitual smoking (2 packs/day for at least 6 months) Comorbid disorders depression Endophenotypes Electroencephalogram (EEG) Event related potential (ERP) Neurophysiological Endophenotypes   S-transform of evoked activity to target in VP3 yields time-frequency characteristics of signa