Linkage analyses of cannabis dependence, craving, and withdrawal in the San Francisco family study

• Published in: American journal of medical genetics. Part B, Neuropsychiatric genetics Neuropsychiatric genetics, 2010-04, Vol.153B (3), p.802-811
• Main Authors: Ehlers, Cindy L., Gizer, Ian R., Vieten, Cassandra, Wilhelmsen, Kirk C.
• Format: Article
• Language: English
• Subjects: Alcoholism; Alcoholism - genetics; Biological and medical sciences; Cannabis; Chromosome 1; Chromosome Mapping; Chromosomes; Classical genetics, quantitative genetics, hybrids; Computer Simulation; dependence; Drug abuse; Drug addiction; Family; Family studies; Female; Fundamental and applied biological sciences. Psychology; Gene polymorphism; Genetic Linkage; Genetics of eukaryotes. Biological and molecular evolution; genome scan; Genomes; Genotype; heritability; Human; Humans; Linkage analysis; Male; marijuana; Marijuana Abuse - genetics; Medical genetics; Medical sciences; Microsatellites; Middle Aged; Phenotype; San Francisco; Substance Withdrawal Syndrome - genetics
• ISSN: 1552-4841; 1552-485X; 1552-485X
• DOI: 10.1002/ajmg.b.31050

Cannabis is the most widely used illicit drug in the United States. There is ample evidence that cannabis use has a heritable component, yet the genes underlying cannabis use disorders are yet to be completely identified. This study's aims were to map susceptibility loci for cannabis use and dependence and two narrower cannabis‐related phenotypes of “craving” and “withdrawal” using a family study design. Participants were 2,524 adults participating in the University of California San Francisco (UCSF) Family Alcoholism Study. DSM‐IV diagnoses of cannabis dependence, as well as indices of cannabis craving and withdrawal, were obtained using a modified version of the Semi‐Structured Assessment for the Genetics of Alcoholism (SSAGA). Genotypes were determined for a panel of 791 microsatellite polymorphisms. Multipoint variance component LOD scores were obtained using SOLAR. Genome‐wide significance for linkage (LOD > 3.0) was not found for the DSM‐IV cannabis dependence diagnosis; however, linkage analyses of cannabis “craving” and the cannabis withdrawal symptom of “nervous, tense, restless, or irritable” revealed five sites with LOD scores over 3.0 on chromosomes 1, 3, 6, 7, and 9. These results identify new regions of the genome associated with cannabis use phenotypes as well as corroborate the importance of several chromosome regions highlighted in previous linkage analyses for other substance dependence phenotypes. © 2009 Wiley‐Liss, Inc.