Understanding the course of Mission Indian alcoholism can help identify unique alcohol-related phenotypes as well as guide the development of treatment and prevention programs in this underserved population.

Alcohol dependence is a leading cause of morbidity and mortality in Native Americans, yet biological factors underlying the disorder in this ethnic group remain elusive. This study's aims were to map susceptibility loci for DSM-III-R alcohol dependence and two narrower alcohol-related phenotypes in Mission Indian families. Each participant gave a blood sample and completed an interview using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) that was used to make alcohol dependence diagnoses and the narrower phenotypes of withdrawal, and drinking severity. Genotypes were determined for a panel 791 microsatellite polymorphisms. Analyses of multipoint variance component LOD scores for the dichotomous DSM-III-R phenotype revealed no peak LOD scores that exceeded 2.0 at any chromosome location. Two chromosomes, 4 and 12, had peak LOD scores that exceeded 2 for the alcohol use severity phenotype and three chromosomes 6, 15, 16 were found to have peaks with LOD scores that exceeded 2 for the withdrawal phenotype. Evidence for linkage to chromosomes 4 and 15, and 16 have been reported previously for alcohol related phenotypes whereas no evidence has as yet been reported for chromosomes 6 and 12. Combined linkage and association analysis suggest that alcohol dehydrogenase 1B gene polymorphisms are partially responsible for the linkage result on chromosome 4 in this population. These results corroborate the importance of several chromosomal regions highlighted in prior segregation studies in alcoholism and further identify new regions of the genome that may be unique to either the restricted phenotypes evaluated or this population of Mission Indians.

These data suggest that effective environmental prevention efforts at reducing underage drinking may be an important strategy to lower the prevalence of alcohol dependence in this high-risk population.

Cannabis is the most widely used illicit drug in the United States, yet the role of genetics in individual symptoms associated with cannabis use disorders has not been evaluated. The purpose of the present set of analyses was to describe the symptomatology and estimate the heritability of DSM-IV criteria/ symptoms of cannabis dependence in a large sample of families. Participants were 2524 adults, participating in the University of California San Francisco (UCSF) Family Study of alcoholism. Seventy percent of the sample had ever used cannabis and 13.9% met DSM-IV criteria for cannabis dependence. Younger age at first cannabis use was found to be significantly associated with a shortened survival to becoming cannabis dependent. Although a greater percentage of men met criteria for cannabis dependence, women were found to demonstrate "telescoping" as indexed by a shorter survival time from initial use to dependence as compared to men. A cannabis withdrawal syndrome was identified in users, the primary symptoms of which were nervousness, appetite change, and sleep disturbance. Cannabis use (h 2 = 0.31) and dependence (h 2 = 0.20), age at first use, individual DSM-IV criteria for dependence, and cannabis-use associated symptoms of depression, trouble concentrating and paranoia were all found to be heritable. These findings suggest that within this population that cannabis use and dependence, as well as individual cannabis dependence symptoms have a significant heritable component, that cannabis dependence is more likely to occur when use Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ContributorsThe submitted manuscript has been read and approved by all authors and all authors concur with the submitted manuscript. Kirk Wilhelmsen and Cassandra Vieten designed the study and wrote the protocol. Phillip Lau, Gina Stouffer and Ian Gizer conducted the statistical analysis. David Gilder did all best final diagnoses of research participants. Cindy Ehlers wrote the first draft of the manuscript and all authors contributed to and have approved the final manuscript. In addition, the authors acknowledge that they have exercised due care in ensuring the integrity of the work, and none of the original material contained in the manuscript has been submitted for consideration nor will any of it be published elsewhere except in abstract form in connection with scientific meetings. Conflict of Interest