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

  • Author(s): Lai, Dongbing;
  • Kapoor, Manav;
  • Wetherill, Leah;
  • Schwandt, Melanie;
  • Ramchandani, Vijay A;
  • Goldman, David;
  • Chao, Michael;
  • Almasy, Laura;
  • Bucholz, Kathleen;
  • Hart, Ronald P;
  • Kamarajan, Chella;
  • Meyers, Jacquelyn L;
  • Nurnberger, John I;
  • Tischfield, Jay;
  • Edenberg, Howard J;
  • Schuckit, Marc;
  • Goate, Alison;
  • Scott, Denise M;
  • Porjesz, Bernice;
  • Agrawal, Arpana;
  • Foroud, Tatiana
  • et al.
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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