An endophenotype approach to the genetics of alcohol dependence: a genome wide association study of fast beta EEG in families of African ancestry

J L Meyers; J Zhang; J C Wang; J Su; S I Kuo; M Kapoor; L Wetherill; S Bertelsen; D Lai; J E Salvatore; C Kamarajan; D Chorlian; A Agrawal; L Almasy; L Bauer; K K Bucholz; G Chan; V Hesselbrock; L Koganti; J Kramer; S Kuperman; N Manz; A Pandey; M Seay; D Scott; R E Taylor; D M Dick; H J Edenberg; A Goate; T Foroud; B Porjesz

doi:10.1038/mp.2016.239

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An endophenotype approach to the genetics of alcohol dependence: a genome wide association study of fast beta EEG in families of African ancestry

Journal article

Peer reviewed

An endophenotype approach to the genetics of alcohol dependence: a genome wide association study of fast beta EEG in families of African ancestry

J L Meyers, J Zhang, J C Wang, J Su, S I Kuo, M Kapoor, L Wetherill, S Bertelsen, D Lai, J E Salvatore, …

Molecular psychiatry, Vol.22(12), pp.1767-1775

12/2017

DOI: 10.1038/mp.2016.239

PMCID: PMC5503794

PMID: 28070124

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Abstract

Fast beta (20-28 Hz) electroencephalogram (EEG) oscillatory activity may be a useful endophenotype for studying the genetics of disorders characterized by neural hyperexcitability, including substance use disorders (SUDs). However, the genetic underpinnings of fast beta EEG have not previously been studied in a population of African-American ancestry (AA). In a sample of 2382 AA individuals from 482 families drawn from the Collaborative Study on the Genetics of Alcoholism (COGA), we performed a genome-wide association study (GWAS) on resting-state fast beta EEG power. To further characterize our genetic findings, we examined the functional and clinical/behavioral significance of GWAS variants. Ten correlated single-nucleotide polymorphisms (SNPs) (r >0.9) located in an intergenic region on chromosome 3q26 were associated with fast beta EEG power at P<5 × 10 . The most significantly associated SNP, rs11720469 (β: -0.124; P<4.5 × 10 ), is also an expression quantitative trait locus for BCHE (butyrylcholinesterase), expressed in thalamus tissue. Four of the genome-wide SNPs were also associated with Diagnostic and Statistical Manual of Mental Disorders Alcohol Dependence in COGA AA families, and two (rs13093097, rs7428372) were replicated in an independent AA sample (Gelernter et al.). Analyses in the AA adolescent/young adult (offspring from COGA families) subsample indicated association of rs11720469 with heavy episodic drinking (frequency of consuming 5+ drinks within 24 h). Converging findings presented in this study provide support for the role of genetic variants within 3q26 in neural and behavioral disinhibition. These novel genetic findings highlight the importance of including AA populations in genetics research on SUDs and the utility of the endophenotype approach in enhancing our understanding of mechanisms underlying addiction susceptibility.

Adult

African Americans - genetics

African Continental Ancestry Group - genetics

Alcohol Drinking - genetics

Alcohol Drinking - physiopathology

Alcoholism - diagnosis

Alcoholism - genetics

Alcoholism - physiopathology

Brain - physiopathology

Butyrylcholinesterase - genetics

Electroencephalography

Endophenotypes

Female

Genetic Predisposition to Disease

Genome-Wide Association Study

Humans

Male

Polymorphism, Single Nucleotide

Details

Title: Subtitle: An endophenotype approach to the genetics of alcohol dependence: a genome wide association study of fast beta EEG in families of African ancestry
Creators: J L Meyers - SUNY Downstate Health Sciences University
J Zhang - SUNY Downstate Health Sciences University
J C Wang - Icahn School of Medicine at Mount Sinai
J Su - Virginia Commonwealth University
S I Kuo - Virginia Commonwealth University
M Kapoor - Icahn School of Medicine at Mount Sinai
L Wetherill - Indiana University
S Bertelsen - Icahn School of Medicine at Mount Sinai
D Lai - Indiana University
J E Salvatore - Virginia Commonwealth University
C Kamarajan - SUNY Downstate Health Sciences University
D Chorlian - SUNY Downstate Health Sciences University
A Agrawal - Washington University in St. Louis
L Almasy - University of Pennsylvania
L Bauer - University of Connecticut
K K Bucholz - Washington University in St. Louis
G Chan - University of Connecticut
V Hesselbrock - University of Connecticut
L Koganti - Icahn School of Medicine at Mount Sinai
J Kramer - University of Iowa
S Kuperman - University of Iowa
N Manz - College of Wooster
A Pandey - SUNY Downstate Health Sciences University
M Seay - SUNY Downstate Health Sciences University
D Scott - Howard University
R E Taylor - Howard University
D M Dick - Virginia Commonwealth University
H J Edenberg - Indiana University
A Goate - Icahn School of Medicine at Mount Sinai
T Foroud - Indiana University
B Porjesz - SUNY Downstate Health Sciences University
Resource Type: Journal article
Publication Details: Molecular psychiatry, Vol.22(12), pp.1767-1775
DOI: 10.1038/mp.2016.239
PMID: 28070124
PMCID: PMC5503794
NLM abbreviation: Mol Psychiatry
ISSN: 1359-4184
eISSN: 1476-5578
Grant note: K01 AA024152 / NIAAA NIH HHS K01 DA037914 / NIDA NIH HHS UL1 TR002345 / NCATS NIH HHS S10 OD018522 / NIH HHS U10 AA008401 / NIAAA NIH HHS L30 DA042455 / NIDA NIH HHS K02 DA032573 / NIDA NIH HHS U01 HG004438 / NHGRI NIH HHS UL1 TR000448 / NCATS NIH HHS T32 AI007172 / NIAID NIH HHS HHSN268200782096C / NHLBI NIH HHS P30 CA091842 / NCI NIH HHS UL1 RR024992 / NCRR NIH HHS L30 AA022519 / NIAAA NIH HHS
Language: English
Date published: 12/2017
Academic Unit: Psychiatry
Record Identifier: 9984293753202771

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