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

Ehlers, Cindy L.a b; Gizer, Ian R.c; Schuckit, Marc A.b; Wilhelmsen, Kirk C.c

doi: 10.1097/YPG.0b013e32833add87
Original Articles

Objective: This study's aims were to map loci linked to self-rating of the effects of alcohol and to determine if there was overlap with loci mapped earlier for other substance dependence phenotypes in an American Indian community at high risk for substance dependence.

Methods: Each participant gave a blood sample and completed a structured diagnostic interview using the Semi Structured Assessment for the Genetics of Alcoholism. Retrospective report of responses to alcohol during the FIRST FIVE TIMES they had ever drank alcohol was estimated from the Self-Rating of the Effects of Alcohol (SRE) questionnaire for each participant. Genotypes were determined for a panel of 791 micro-satellite polymorphisms in 381 members of multiplex families using SOLAR.

Results: Analyses of multipoint variance component Log of Odds (LOD) scores, for the FIRST FIVE TIMES phenotype, revealed two loci that had a LOD score greater than 3.0 on chromosomes 6 and 9. In addition, three locations were identified with LOD scores above 2.0 on chromosomes 10, 12, 17.

Conclusion: These results corroborate the importance of regions on chromosome 6 and 9 highlighted in earlier segregation studies in this and other populations for substance dependence-related phenotypes, as well as an area on chromosome 10 earlier identified for the FIRST FIVE TIMES phenotype in the collaborative study on the genetics of alcoholism. These studies additionally lend further support the construct that the SRE may represent an important endophenotype associated with alcohol and other substance dependence.

aDepartment of Molecular and Integrative Neurosciences, The Scripps Research Institute

bDepartment of Psychiatry, University of California San Diego, La Jolla, California

cDepartment of Genetics and Neurology, The Carolina Center for Genome Sciences and the Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, North Carolina, USA

Correspondence to Professor Cindy L. Ehlers, PhD, The Scripps Research Institute, Department of Molecular and Integrative Neurosciences, 10550 North Torrey Pines Road, SP30-1501, La Jolla, CA 92037, USA

Tel: +1 858 784 7058; fax: +1 858 784 7409; e-mail: cindye@scripps.edu

Received 9 November 2009 Revised 26 February 2010 Accepted 10 April 2010

© 2010 Lippincott Williams & Wilkins, Inc.