Alcohol dependence with comorbid drug dependence: genetic and phenotypic associations suggest a more severe form of the disorder with stronger genetic contribution to risk.
BACKGROUND
Twin data suggest that alcohol dependence comorbid with illicit drug dependence represents a more heritable form of the disorder. In the Collaborative Study on the Genetics of Alcoholism sample, approximately half the alcohol-dependent individuals also meet diagnostic criteria for illicit drug dependence. In this study, we tested for heterogeneity in the association between the muscarinic acetylcholine M2 receptor gene (CHRM2) and alcohol dependence, reported previously in the full sample, among the subgroups of alcohol-dependent individuals with and without comorbid drug dependence.


METHODS
Family-based association tests were conducted separately (a) in individuals with alcohol dependence with comorbid drug dependence (n = 477) and (b) in individuals with alcohol dependence without comorbid drug dependence (n = 433). These subgroups were subsequently compared on other phenotypic characteristics.


RESULTS
The evidence for association between CHRM2 and alcohol dependence came entirely from the subgroup of individuals with comorbid drug dependence. There was no evidence of association with CHRM2 among the alcohol-dependent individuals without drug dependence. Subsequent phenotypic analyses suggest that the subgroup of alcohol-dependent individuals with comorbid drug dependence differ on a number of other phenotypic characteristics, including several measures of the severity of their alcohol problems, personality traits and comorbid psychiatric disorders.


CONCLUSIONS
These analyses provide specific genetic evidence suggesting that alcohol dependence with comorbid drug dependence represents a particularly severe form of the disorder, with higher genetic contribution to vulnerability.
Dick
Danielle M
DM
Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri 63110, USA. dickd@psychiatry.wustl.edu
Agrawal
Arpana
A
Wang
Jen C
JC
Hinrichs
Anthony
A
Bertelsen
Sarah
S
Bucholz
Kathleen K
KK
Schuckit
Marc
M
Kramer
John
J
Nurnberger
John
J
Tischfield
Jay
J
Edenberg
Howard J
HJ
Goate
Alison
A
Bierut
Laura J
LJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000437:Alcoholism / Q000453:epidemiology / Q000235:genetics*; D015897:Comorbidity; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D043585:Receptor, Muscarinic M2 / Q000235:genetics*; D012307:Risk Factors; D019966:Substance-Related Disorders / Q000453:epidemiology / Q000235:genetics*
C487078:CHRM2 protein, human; D043585:Receptor, Muscarinic M2