Heritability and a genome-wide linkage analysis of a Type II/B cluster construct for cannabis dependence in an American Indian community.
Subtyping of substance dependence disorders holds promise for a number of important research areas including phenotyping for genetic studies, characterizing clinical course, and matching treatment and prevention strategies. This study sought to investigate whether a dichotomous construct similar to Babor's Types A/B and Cloninger's Types I/II for alcohol dependence can be identified for cannabis dependence in a Native American sample. In addition, heritability of this construct and its behavior in a genetic linkage analyses were evaluated. Information on cannabis use and dependence symptoms and other psychiatric disorders was obtained using the Semi-Structured Assessment for the Genetics of Alcoholism from a community sample of 606 American Indians. Hierarchical average linkage and K means cluster analysis was used, and a three-cluster solution was found to generate the best separation of variables. Ninety-one per cent of cannabis-dependent participants fell into one of the two subtypes: Type A/I cluster (n = 114, 56%) and Type B/II cluster (n = 70, 35%). Heritability (estimated using Sequential Oligogenic Linkage Analysis Routines) was only significant for the Type B/II cluster (h(2) = 0.44, SE = 0.18, P < 0.01). Evidence for linkage was found for the Type B/II cluster (versus no diagnosis) on chromosome 16 [at 139 centimorgans (cM), Log of the Odds (LOD) score = 4.4], and on chromosome 19 (at 74 cM, LOD score = 6.4). Regions of interest for this phenotype (LOD > 1.5) were also located on chromosomes 14, 21, 22. These findings suggest that a Type B/II cannabis dependence phenotype can be identified in this population and that it is in part heritable and linked to areas of the genome identified previously for drug dependence phenotypes in this population as well as in other studies.
Department of Molecular and Integrative Neurosciences, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. cindye@scripps.edu
Cindy L
CL
Ehlers
David A
DA
Gilder
Ian R
IR
Gizer
Kirk C
KC
Wilhelmsen
D000328:Adult; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D016000:Cluster Analysis; D003430:Cross-Sectional Studies; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D007198:Indians, North American / Q000235:genetics* / Q000706:statistics & numerical data; D008126:Lod Score; D008297:Male; D002189:Marijuana Abuse / Q000145:classification / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D012307:Risk Factors; D019966:Substance-Related Disorders / Q000145:classification / Q000235:genetics; D055815:Young Adult