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

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

doi:10.1002/ajmg.b.32805

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

Am J Med Genet B Neuropsychiatr Genet. 2021 Apr;186(3):151-161. doi: 10.1002/ajmg.b.32805. Epub 2020 Jul 11.

Authors

Dongbing Lai¹, Manav Kapoor², Leah Wetherill¹, Melanie Schwandt³, Vijay A Ramchandani⁴, David Goldman³, Michael Chao², Laura Almasy⁵, Kathleen Bucholz⁶, Ronald P Hart⁷, Chella Kamarajan⁸, Jacquelyn L Meyers⁸, John I Nurnberger^{1

9}, Jay Tischfield¹⁰, Howard J Edenberg^{1

11}, Marc Schuckit¹², Alison Goate², Denise M Scott¹³, Bernice Porjesz⁸, Arpana Agrawal⁶, Tatiana Foroud¹

Affiliations

¹ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
² Department of Neuroscience, Icahn School of Medicine at Mt. Sinai, New York, New York, USA.
³ Office of the Clinical Director, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA.
⁴ Section on Human Psychopharmacology, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA.
⁵ Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
⁶ Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.
⁷ Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey, USA.
⁸ Henri Begleiter Neurodynamics Lab, Department of Psychiatry, State University of New York, Downstate Medical Center, Brooklyn, New York, USA.
⁹ Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹⁰ Department of Genetics and the Human Genetics Institute of New Jersey, Rutgers University, Piscataway, New Jersey, USA.
¹¹ Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹² Department of Psychiatry, University of California, San Diego Medical School, San Diego, California, USA.
¹³ Departments of Pediatrics and Human Genetics, Howard University, Washington, District of Columbia, USA.

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.

Keywords: African American; DSM-IV alcohol dependence; admixture mapping; criterion count; response to ethanol.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Alcoholism / etiology
Alcoholism / genetics*
Alcoholism / physiopathology
Black or African American / genetics*
Case-Control Studies
Diagnostic and Statistical Manual of Mental Disorders
Ethanol / pharmacology*
Genetic Predisposition to Disease*
Genome-Wide Association Study*
Humans
Polymorphism, Single Nucleotide*
Retrospective Studies
Self Report*
White People

Substances

Ethanol

Abstract

Publication types

MeSH terms

Substances

Grants and funding