TY - JOUR
T1 - Genome-wide admixture mapping of DSM-IV alcohol dependence, criterion count, and the self-rating of the effects of ethanol in African American populations
AU - Lai, Dongbing
AU - Kapoor, Manav
AU - Wetherill, Leah
AU - Schwandt, Melanie
AU - Ramchandani, Vijay A.
AU - Goldman, David
AU - Chao, Michael
AU - Almasy, Laura
AU - Bucholz, Kathleen
AU - Hart, Ronald P.
AU - Kamarajan, Chella
AU - Meyers, Jacquelyn L.
AU - Nurnberger, John I.
AU - Tischfield, Jay
AU - Edenberg, Howard J.
AU - Schuckit, Marc
AU - Goate, Alison
AU - Scott, Denise M.
AU - Porjesz, Bernice
AU - Agrawal, Arpana
AU - Foroud, Tatiana
N1 - Publisher Copyright:
© 2020 Wiley Periodicals, LLC.
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
KW - African American
KW - DSM-IV alcohol dependence
KW - admixture mapping
KW - criterion count
KW - response to ethanol
UR - http://www.scopus.com/inward/record.url?scp=85087707202&partnerID=8YFLogxK
U2 - 10.1002/ajmg.b.32805
DO - 10.1002/ajmg.b.32805
M3 - Article
C2 - 32652861
AN - SCOPUS:85087707202
SN - 1552-4841
VL - 186
SP - 151
EP - 161
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
IS - 3
ER -