Genome-wide association studies of alcohol dependence, DSM-IV criterion count and individual criteria

Dongbing Lai, Leah Wetherill, Sarah Bertelsen, Caitlin E. Carey, Chella Kamarajan, Manav Kapoor, Jacquelyn L. Meyers, Andrey P. Anokhin, David A. Bennett, Kathleen K. Bucholz, Katharine K. Chang, Philip L. De Jager, Danielle M. Dick, Victor Hesselbrock, John Kramer, Samuel Kuperman, John Nurnberger, Towfique Raj, Marc Schuckit, Denise M. Scott & 9 others Robert E. Taylor, Jay Tischfield, Ahmad R. Hariri, Howard Edenberg, Arpana Agrawal, Ryan Bogdan, Bernice Porjesz, Alison M. Goate, Tatiana Foroud

Research output: Contribution to journalArticle

Abstract

Genome-wide association studies (GWAS) of alcohol dependence (AD) have reliably identified variation within alcohol metabolizing genes (eg, ADH1B) but have inconsistently located other signals, which may be partially attributable to symptom heterogeneity underlying the disorder. We conducted GWAS of DSM-IV AD (primary analysis), DSM-IV AD criterion count (secondary analysis), and individual dependence criteria (tertiary analysis) among 7418 (1121 families) European American (EA) individuals from the Collaborative Study on the Genetics of Alcoholism (COGA). Trans-ancestral meta-analyses combined these results with data from 3175 (585 families) African-American (AA) individuals from COGA. In the EA GWAS, three loci were genome-wide significant: rs1229984 in ADH1B for AD criterion count (P = 4.16E−11) and Desire to cut drinking (P = 1.21E−11); rs188227250 (chromosome 8, Drinking more than intended, P = 6.72E−09); rs1912461 (chromosome 15, Time spent drinking, P = 1.77E−08). In the trans-ancestral meta-analysis, rs1229984 was associated with multiple phenotypes and two additional loci were genome-wide significant: rs61826952 (chromosome 1, DSM-IV AD, P = 8.42E−11); rs7597960 (chromosome 2, Time spent drinking, P = 1.22E−08). Associations with rs1229984 and rs18822750 were replicated in independent datasets. Polygenic risk scores derived from the EA GWAS of AD predicted AD in two EA datasets (P <.01; 0.61%-1.82% of variance). Identified novel variants (ie, rs1912461, rs61826952) were associated with differential central evoked theta power (loss − gain; P =.0037) and reward-related ventral striatum reactivity (P =.008), respectively. This study suggests that studying individual criteria may unveil new insights into the genetic etiology of AD liability.

Original languageEnglish (US)
Article numbere12579
JournalGenes, Brain and Behavior
Volume18
Issue number6
DOIs
StatePublished - Jul 1 2019

Fingerprint

Genome-Wide Association Study
Diagnostic and Statistical Manual of Mental Disorders
Alcoholism
Drinking
Meta-Analysis
Genome
Chromosomes, Human, Pair 15
Chromosomes, Human, Pair 8
Chromosomes, Human, Pair 2
Chromosomes, Human, Pair 1
Reward
African Americans
Alcohols
Phenotype

Keywords

  • alcohol dependence
  • DSM-IV alcohol dependence criterion
  • DSM-IV criterion count
  • DSM-IV individual criteria
  • event-related theta oscillations
  • functional magnetic resonance imaging
  • genome-wide association study
  • item response analysis
  • meta-analysis
  • polygenic risk score

ASJC Scopus subject areas

  • Genetics
  • Neurology
  • Behavioral Neuroscience

Cite this

Genome-wide association studies of alcohol dependence, DSM-IV criterion count and individual criteria. / Lai, Dongbing; Wetherill, Leah; Bertelsen, Sarah; Carey, Caitlin E.; Kamarajan, Chella; Kapoor, Manav; Meyers, Jacquelyn L.; Anokhin, Andrey P.; Bennett, David A.; Bucholz, Kathleen K.; Chang, Katharine K.; De Jager, Philip L.; Dick, Danielle M.; Hesselbrock, Victor; Kramer, John; Kuperman, Samuel; Nurnberger, John; Raj, Towfique; Schuckit, Marc; Scott, Denise M.; Taylor, Robert E.; Tischfield, Jay; Hariri, Ahmad R.; Edenberg, Howard; Agrawal, Arpana; Bogdan, Ryan; Porjesz, Bernice; Goate, Alison M.; Foroud, Tatiana.

In: Genes, Brain and Behavior, Vol. 18, No. 6, e12579, 01.07.2019.

Research output: Contribution to journalArticle

Lai, D, Wetherill, L, Bertelsen, S, Carey, CE, Kamarajan, C, Kapoor, M, Meyers, JL, Anokhin, AP, Bennett, DA, Bucholz, KK, Chang, KK, De Jager, PL, Dick, DM, Hesselbrock, V, Kramer, J, Kuperman, S, Nurnberger, J, Raj, T, Schuckit, M, Scott, DM, Taylor, RE, Tischfield, J, Hariri, AR, Edenberg, H, Agrawal, A, Bogdan, R, Porjesz, B, Goate, AM & Foroud, T 2019, 'Genome-wide association studies of alcohol dependence, DSM-IV criterion count and individual criteria', Genes, Brain and Behavior, vol. 18, no. 6, e12579. https://doi.org/10.1111/gbb.12579
Lai, Dongbing ; Wetherill, Leah ; Bertelsen, Sarah ; Carey, Caitlin E. ; Kamarajan, Chella ; Kapoor, Manav ; Meyers, Jacquelyn L. ; Anokhin, Andrey P. ; Bennett, David A. ; Bucholz, Kathleen K. ; Chang, Katharine K. ; De Jager, Philip L. ; Dick, Danielle M. ; Hesselbrock, Victor ; Kramer, John ; Kuperman, Samuel ; Nurnberger, John ; Raj, Towfique ; Schuckit, Marc ; Scott, Denise M. ; Taylor, Robert E. ; Tischfield, Jay ; Hariri, Ahmad R. ; Edenberg, Howard ; Agrawal, Arpana ; Bogdan, Ryan ; Porjesz, Bernice ; Goate, Alison M. ; Foroud, Tatiana. / Genome-wide association studies of alcohol dependence, DSM-IV criterion count and individual criteria. In: Genes, Brain and Behavior. 2019 ; Vol. 18, No. 6.
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T1 - Genome-wide association studies of alcohol dependence, DSM-IV criterion count and individual criteria

AU - Lai, Dongbing

AU - Wetherill, Leah

AU - Bertelsen, Sarah

AU - Carey, Caitlin E.

AU - Kamarajan, Chella

AU - Kapoor, Manav

AU - Meyers, Jacquelyn L.

AU - Anokhin, Andrey P.

AU - Bennett, David A.

AU - Bucholz, Kathleen K.

AU - Chang, Katharine K.

AU - De Jager, Philip L.

AU - Dick, Danielle M.

AU - Hesselbrock, Victor

AU - Kramer, John

AU - Kuperman, Samuel

AU - Nurnberger, John

AU - Raj, Towfique

AU - Schuckit, Marc

AU - Scott, Denise M.

AU - Taylor, Robert E.

AU - Tischfield, Jay

AU - Hariri, Ahmad R.

AU - Edenberg, Howard

AU - Agrawal, Arpana

AU - Bogdan, Ryan

AU - Porjesz, Bernice

AU - Goate, Alison M.

AU - Foroud, Tatiana

PY - 2019/7/1

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N2 - Genome-wide association studies (GWAS) of alcohol dependence (AD) have reliably identified variation within alcohol metabolizing genes (eg, ADH1B) but have inconsistently located other signals, which may be partially attributable to symptom heterogeneity underlying the disorder. We conducted GWAS of DSM-IV AD (primary analysis), DSM-IV AD criterion count (secondary analysis), and individual dependence criteria (tertiary analysis) among 7418 (1121 families) European American (EA) individuals from the Collaborative Study on the Genetics of Alcoholism (COGA). Trans-ancestral meta-analyses combined these results with data from 3175 (585 families) African-American (AA) individuals from COGA. In the EA GWAS, three loci were genome-wide significant: rs1229984 in ADH1B for AD criterion count (P = 4.16E−11) and Desire to cut drinking (P = 1.21E−11); rs188227250 (chromosome 8, Drinking more than intended, P = 6.72E−09); rs1912461 (chromosome 15, Time spent drinking, P = 1.77E−08). In the trans-ancestral meta-analysis, rs1229984 was associated with multiple phenotypes and two additional loci were genome-wide significant: rs61826952 (chromosome 1, DSM-IV AD, P = 8.42E−11); rs7597960 (chromosome 2, Time spent drinking, P = 1.22E−08). Associations with rs1229984 and rs18822750 were replicated in independent datasets. Polygenic risk scores derived from the EA GWAS of AD predicted AD in two EA datasets (P <.01; 0.61%-1.82% of variance). Identified novel variants (ie, rs1912461, rs61826952) were associated with differential central evoked theta power (loss − gain; P =.0037) and reward-related ventral striatum reactivity (P =.008), respectively. This study suggests that studying individual criteria may unveil new insights into the genetic etiology of AD liability.

AB - Genome-wide association studies (GWAS) of alcohol dependence (AD) have reliably identified variation within alcohol metabolizing genes (eg, ADH1B) but have inconsistently located other signals, which may be partially attributable to symptom heterogeneity underlying the disorder. We conducted GWAS of DSM-IV AD (primary analysis), DSM-IV AD criterion count (secondary analysis), and individual dependence criteria (tertiary analysis) among 7418 (1121 families) European American (EA) individuals from the Collaborative Study on the Genetics of Alcoholism (COGA). Trans-ancestral meta-analyses combined these results with data from 3175 (585 families) African-American (AA) individuals from COGA. In the EA GWAS, three loci were genome-wide significant: rs1229984 in ADH1B for AD criterion count (P = 4.16E−11) and Desire to cut drinking (P = 1.21E−11); rs188227250 (chromosome 8, Drinking more than intended, P = 6.72E−09); rs1912461 (chromosome 15, Time spent drinking, P = 1.77E−08). In the trans-ancestral meta-analysis, rs1229984 was associated with multiple phenotypes and two additional loci were genome-wide significant: rs61826952 (chromosome 1, DSM-IV AD, P = 8.42E−11); rs7597960 (chromosome 2, Time spent drinking, P = 1.22E−08). Associations with rs1229984 and rs18822750 were replicated in independent datasets. Polygenic risk scores derived from the EA GWAS of AD predicted AD in two EA datasets (P <.01; 0.61%-1.82% of variance). Identified novel variants (ie, rs1912461, rs61826952) were associated with differential central evoked theta power (loss − gain; P =.0037) and reward-related ventral striatum reactivity (P =.008), respectively. This study suggests that studying individual criteria may unveil new insights into the genetic etiology of AD liability.

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KW - DSM-IV alcohol dependence criterion

KW - DSM-IV criterion count

KW - DSM-IV individual criteria

KW - event-related theta oscillations

KW - functional magnetic resonance imaging

KW - genome-wide association study

KW - item response analysis

KW - meta-analysis

KW - polygenic risk score

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