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. KramerS. Kuperman, N. Manz, A. Pandey, M. Seay, D. Scott, R. E. Taylor, D. M. Dick, Howard Edenberg, A. Goate, Tatiana Foroud, B. Porjesz

Research output: Contribution to journalArticle

12 Citations (Scopus)

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) (r2>0.9) located in an intergenic region on chromosome 3q26 were associated with fast beta EEG power at P<5 × 10-8. The most significantly associated SNP, rs11720469 (β: −0.124; P<4.5 × 10-9), 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.Molecular Psychiatry advance online publication, 10 January 2017; doi:10.1038/mp.2016.239.

Original languageEnglish (US)
JournalMolecular Psychiatry
DOIs
StateAccepted/In press - Jan 10 2017

Fingerprint

Endophenotypes
Genome-Wide Association Study
Alcoholism
Electroencephalography
Single Nucleotide Polymorphism
Substance-Related Disorders
Butyrylcholinesterase
Genetic Research
Inborn Genetic Diseases
Intergenic DNA
Quantitative Trait Loci
Population Genetics
Adult Children
Thalamus
Diagnostic and Statistical Manual of Mental Disorders
African Americans
Drinking
Psychiatry
Publications
Young Adult

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

Cite this

An endophenotype approach to the genetics of alcohol dependence : a genome wide association study of fast beta EEG in families of African ancestry. / Meyers, J. L.; Zhang, J.; Wang, J. C.; Su, J.; Kuo, S. I.; Kapoor, M.; Wetherill, L.; Bertelsen, S.; Lai, D.; Salvatore, J. E.; Kamarajan, C.; Chorlian, D.; Agrawal, A.; Almasy, L.; Bauer, L.; Bucholz, K. K.; Chan, G.; Hesselbrock, V.; Koganti, L.; Kramer, J.; Kuperman, S.; Manz, N.; Pandey, A.; Seay, M.; Scott, D.; Taylor, R. E.; Dick, D. M.; Edenberg, Howard; Goate, A.; Foroud, Tatiana; Porjesz, B.

In: Molecular Psychiatry, 10.01.2017.

Research output: Contribution to journalArticle

Meyers, JL, Zhang, J, Wang, JC, Su, J, Kuo, SI, Kapoor, M, Wetherill, L, Bertelsen, S, Lai, D, Salvatore, JE, Kamarajan, C, Chorlian, D, Agrawal, A, Almasy, L, Bauer, L, Bucholz, KK, Chan, G, Hesselbrock, V, Koganti, L, Kramer, J, Kuperman, S, Manz, N, Pandey, A, Seay, M, Scott, D, Taylor, RE, Dick, DM, Edenberg, H, Goate, A, Foroud, T & Porjesz, B 2017, 'An endophenotype approach to the genetics of alcohol dependence: a genome wide association study of fast beta EEG in families of African ancestry', Molecular Psychiatry. https://doi.org/10.1038/mp.2016.239
Meyers, J. L. ; Zhang, J. ; Wang, J. C. ; Su, J. ; Kuo, S. I. ; Kapoor, M. ; Wetherill, L. ; Bertelsen, S. ; Lai, D. ; Salvatore, J. E. ; Kamarajan, C. ; Chorlian, D. ; Agrawal, A. ; Almasy, L. ; Bauer, L. ; Bucholz, K. K. ; Chan, G. ; Hesselbrock, V. ; Koganti, L. ; Kramer, J. ; Kuperman, S. ; Manz, N. ; Pandey, A. ; Seay, M. ; Scott, D. ; Taylor, R. E. ; Dick, D. M. ; Edenberg, Howard ; Goate, A. ; Foroud, Tatiana ; Porjesz, B. / An endophenotype approach to the genetics of alcohol dependence : a genome wide association study of fast beta EEG in families of African ancestry. In: Molecular Psychiatry. 2017.
@article{d9c6b6e52e414b3c8a0dddadbd73667c,
title = "An endophenotype approach to the genetics of alcohol dependence: a genome wide association study of fast beta EEG in families of African ancestry",
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) (r2>0.9) located in an intergenic region on chromosome 3q26 were associated with fast beta EEG power at P<5 × 10-8. The most significantly associated SNP, rs11720469 (β: −0.124; P<4.5 × 10-9), 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.Molecular Psychiatry advance online publication, 10 January 2017; doi:10.1038/mp.2016.239.",
author = "Meyers, {J. L.} and J. Zhang and Wang, {J. C.} and J. Su and Kuo, {S. I.} and M. Kapoor and L. Wetherill and S. Bertelsen and D. Lai and Salvatore, {J. E.} and C. Kamarajan and D. Chorlian and A. Agrawal and L. Almasy and L. Bauer and Bucholz, {K. K.} and G. Chan and V. Hesselbrock and L. Koganti and J. Kramer and S. Kuperman and N. Manz and A. Pandey and M. Seay and D. Scott and Taylor, {R. E.} and Dick, {D. M.} and Howard Edenberg and A. Goate and Tatiana Foroud and B. Porjesz",
year = "2017",
month = "1",
day = "10",
doi = "10.1038/mp.2016.239",
language = "English (US)",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - An endophenotype approach to the genetics of alcohol dependence

T2 - a genome wide association study of fast beta EEG in families of African ancestry

AU - Meyers, J. L.

AU - Zhang, J.

AU - Wang, J. C.

AU - Su, J.

AU - Kuo, S. I.

AU - Kapoor, M.

AU - Wetherill, L.

AU - Bertelsen, S.

AU - Lai, D.

AU - Salvatore, J. E.

AU - Kamarajan, C.

AU - Chorlian, D.

AU - Agrawal, A.

AU - Almasy, L.

AU - Bauer, L.

AU - Bucholz, K. K.

AU - Chan, G.

AU - Hesselbrock, V.

AU - Koganti, L.

AU - Kramer, J.

AU - Kuperman, S.

AU - Manz, N.

AU - Pandey, A.

AU - Seay, M.

AU - Scott, D.

AU - Taylor, R. E.

AU - Dick, D. M.

AU - Edenberg, Howard

AU - Goate, A.

AU - Foroud, Tatiana

AU - Porjesz, B.

PY - 2017/1/10

Y1 - 2017/1/10

N2 - 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) (r2>0.9) located in an intergenic region on chromosome 3q26 were associated with fast beta EEG power at P<5 × 10-8. The most significantly associated SNP, rs11720469 (β: −0.124; P<4.5 × 10-9), 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.Molecular Psychiatry advance online publication, 10 January 2017; doi:10.1038/mp.2016.239.

AB - 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) (r2>0.9) located in an intergenic region on chromosome 3q26 were associated with fast beta EEG power at P<5 × 10-8. The most significantly associated SNP, rs11720469 (β: −0.124; P<4.5 × 10-9), 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.Molecular Psychiatry advance online publication, 10 January 2017; doi:10.1038/mp.2016.239.

UR - http://www.scopus.com/inward/record.url?scp=85008645116&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85008645116&partnerID=8YFLogxK

U2 - 10.1038/mp.2016.239

DO - 10.1038/mp.2016.239

M3 - Article

C2 - 28070124

AN - SCOPUS:85008645116

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

ER -