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Population admixture modulates risk for alcohol dependence |
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| Authors: | Lingjun Zuo Xingguang Luo Jennifer B Listman Henry R Kranzler Shuang Wang Raymond F Anton Hilary P Blumberg Murray B Stein Godfrey D Pearlson Jonathan Covault Dennis S Charney Daniel P van Kammen Lawrence H Price Jaakko Lappalainen Joyce Cramer John H Krystal Joel Gelernter |
| Institution: | 1. Department of Psychiatry, Yale University School of Medicine, VA Psychiatry 116A2, 950 Campbell Avenue, West Haven, CT, 06516, USA 2. VA Connecticut Healthcare System, West Haven Campus, West Haven, CT, USA 3. Department of Anthropology, New York University, New York, NY, USA 4. Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, USA 5. Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA 6. Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA 7. Departments of Psychiatry and Family and Preventive Medicine, University of California, La Jolla, San Diego, CA, USA 8. Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA 9. Clinical Development, ACADIA Pharmaceuticals, San Diego, CA, USA 10. Department of Psychiatry and Human Behavior, Butler Hospital, Warren Alpert Medical School of Brown University, Providence, RI, USA 11. Department of Genetics, Yale University School of Medicine, New Haven, CT, USA 12. Department of Neurobiology, Yale University School of Medicine, New Haven, CT, USA |
| Abstract: | The admixture of different ancestral populations in America may have important implications for the risk for psychiatric disorders, as it appears to have for other medical disorders. The present study investigated the role of population admixture in risk for several psychiatric disorders in European-Americans (EAs) and African-Americans (AAs). This is a multisite study with 3,792 subjects recruited from across the United States, including 3,119 EAs and 673 AAs. These subjects included healthy controls and those with substance dependence (SD) including alcohol dependence (AD), cocaine dependence, and opioid dependence], social phobia, affective disorders, and schizophrenia. In addition, DNA was included from 78 West Africans. The degree of admixture for each subject was estimated by analysis of a set of ancestry-informative genetic markers using the program STRUCTURE, and was compared between cases and controls. As noted previously, the degree of admixture in AAs was higher than EAs. In EAs, the degree of admixture (with African ancestry) was significantly lower in patients with SD (mainly AD) than controls (P = 0.009 for SD; P = 0.008 for AD). This finding suggests that population admixture may modulate risk for alcohol dependence. Population admixture might protect against alcohol dependence by increasing average heterozygosity and reducing the risk of deleterious recessive alleles. We cannot exclude the possibility that the results might have been influenced by selection bias due to the multisite nature of the study. |
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