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

Abstract

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 2524 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, 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.

Genome-wide scan for self-rating of the effects of alcohol in American Indians

“…This site is near a location (35 cM) that has been reported previously to be linked to cannabis craving (Ehlers et al ., 2009b) in the San Francisco Family Alcoholism study. Additionally, a location near this area on chromosome 9 was identified in a South West Indian population for an alcohol dependence phenotype (Long et al, 1998).…”

“…The lifetime prevalence of substance dependence in this Indian population is high and evidence for heritability and linkage to specific chromosome locations and associations with candidate genes has been demonstrated (see Wall et al, 2003; Ehlers et al, 2004b, 2006b, 2007a,b,c, 2008a,b, 2009a,b, 2010a; Ehlers and Wilhelmsen, 2005, 2007; Wilhelmsen and Ehlers, 2005). The current study’s aims were to: (1) map loci linked to SRE phenotypes and (2) to determine if there was overlap of the loci identified for SRE phenotypes and loci previously mapped for alcohol and other substance dependence in this American Indian community.…”

The Genetic Basis Of The Comorbidity Between Cannabis Use And Major Depression

“…This meta-analysis also observed SNP-based heritability estimates (between 13-20%) lower than twin-based estimations [22], possibly indicating rare variants are also important in this phenotype. Nevertheless, linkage studies (which are ostensibly able to capture both common and rarer variation due to the familybased design) are yet to identify replicated linkage signals for cannabis use [23][24][25].…”

Cannabis : usage et dépendance

“…La précocité de la consommation de cannabis est également prédictive de dépendance ultérieure comme l'ont montré plusieurs études longitudinales telles que les études NHSDA [6], University of California San Francisco (UCSF), Family Study of alcoholism [8] ainsi que les effets subjectifs positifs ressentis lors des 1ères prises (« se sentir content », « se sentir relaxé », « rire », etc.) [9].…”

“…Les études d'épidémiologie génétiques, en particulier les études d'agrégation familiale et les études de jumeaux ont estimé l'héritabilité de la dépendance au cannabis entre 50 et 59 % selon les études [13][14][15]. Ces facteurs de risque peuvent être spécifiques au cannabis ou communs à l'ensemble des addictions [8,14,16].…”