Genome-wide admixture mapping of DSM-IV alcohol dependence, criterion count, and the self-rating of the effects of ethanol in African American populations

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2021-04
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English
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Medical and Molecular Genetics, School of Medicine
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Wiley
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Abstract

African Americans (AA) have lower prevalence of alcohol dependence and higher subjective response to alcohol than European Americans. Genome-wide association studies (GWAS) have identified genes/variants associated with alcohol dependence specifically in AA; however, the sample sizes are still not large enough to detect variants with small effects. Admixture mapping is an alternative way to identify alcohol dependence genes/variants that may be unique to AA. In this study, we performed the first admixture mapping of DSM-IV alcohol dependence diagnosis, DSM-IV alcohol dependence criterion count, and two scores from the self-rating of effects of ethanol (SRE) as measures of response to alcohol: the first five times of using alcohol (SRE-5) and average of SRE across three times (SRE-T). Findings revealed a region on chromosome 4 that was genome-wide significant for SRE-5 (p value = 4.18E-05). Fine mapping did not identify a single causal variant to be associated with SRE-5; instead, conditional analysis concluded that multiple variants collectively explained the admixture mapping signal. PPARGC1A, a gene that has been linked to alcohol consumption in previous studies, is located in this region. Our finding suggests that admixture mapping is a useful tool to identify genes/variants that may have been missed by current GWAS approaches in admixed populations.

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Lai, D., Kapoor, M., Wetherill, L., Schwandt, M., Ramchandani, V. A., Goldman, D., Chao, M., Almasy, L., Bucholz, K., Hart, R. P., Kamarajan, C., Meyers, J. L., Nurnberger, J. I., Tischfield, J., Edenberg, H. J., Schuckit, M., Goate, A., Scott, D. M., Porjesz, B., … Foroud, T. (2021). Genome-wide admixture mapping of DSM-IV alcohol dependence, criterion count, and the self-rating of the effects of ethanol in African American populations. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 186(3), 151–161. https://doi.org/10.1002/ajmg.b.32805
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American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
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