Genomic screen for loci associated with alcohol dependence in Mission Indians

Authors

  • Cindy L. Ehlers,

    Corresponding author
    1. Department of Neuropharmacology, The Scripps Research Institute, University of California, San Diego, California
    2. Department of Psychiatry, University of California, San Diego, California
    3. Department of Neurology, University of California at San Francisco, San Francisco, California
    • The Scripps Research Institute, CVN-14, 10550 North Torrey Pines Road, La Jolla, CA 92037.
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  • David A. Gilder,

    1. Department of Neuropharmacology, The Scripps Research Institute, University of California, San Diego, California
    2. Department of Psychiatry, University of California, San Diego, California
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  • Tamara L. Wall,

    1. Department of Neuropharmacology, The Scripps Research Institute, University of California, San Diego, California
    2. Department of Psychiatry, University of California, San Diego, California
    3. VA San Diego, Healthcare System La Jolla, La Jolla, California
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  • Evelyn Phillips,

    1. Department of Neuropharmacology, The Scripps Research Institute, University of California, San Diego, California
    2. Department of Psychiatry, University of California, San Diego, California
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  • Heidi Feiler,

    1. Ernest Gallo Clinic and Research Center, Emeryville, California
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  • Kirk C. Wilhelmsen

    1. Ernest Gallo Clinic and Research Center, Emeryville, California
    2. Department of Neurology, University of California at San Francisco, San Francisco, California
    3. Department of Genetics and Neurology, University of North Carolina, Chapel Hill, North Carolina
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Abstract

Alcohol dependence is a leading cause of morbidity and mortality in Native Americans, yet biological factors underlying the disorder in this ethnic group remain illusive. 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. © 2004 Wiley-Liss, Inc.

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