TY - JOUR
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 I.
AU - Raj, Towfique
AU - Schuckit, Marc
AU - Scott, Denise M.
AU - Taylor, Robert E.
AU - Tischfield, Jay
AU - Hariri, Ahmad R.
AU - Edenberg, Howard J.
AU - Agrawal, Arpana
AU - Bogdan, Ryan
AU - Porjesz, Bernice
AU - Goate, Alison M.
AU - Foroud, Tatiana
N1 - Funding Information:
A.A. receives additional funding support from NIDA (DA032573). A.P.A. receives additional funding support from NIH (HD083614, DA040716, DA038834). R.B. receives additional funding support from NIH (AG052564, HD083614, AG045231). C.E.C. received additional funding support from the National Science Foundation (DGE-1143954) and the Mr and Mrs Spencer T. Olin Fellowship Program. D.M.D. receives additional funding from National Institute on Alcohol Abuse and Alcoholism (K02AA018755). A.R.H. receives additional funding support from NIH (R01-DA031579 and R01-AG049789). J.L.M. receives additional funding support from NIDA (K01DA037914).
Funding Information:
This national collaborative study is supported by NIH Grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA). Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to the Johns Hopkins University, contract number HHSN268201200008I. The Duke Neurogenetics Study is supported by Duke University and the National Institutes of Health (NIH) (R01-DA033369). A.A. receives additional funding support from NIDA (DA032573). A.P.A. receives additional funding support from NIH (HD083614, DA040716, DA038834). R.B. receives additional funding support from NIH (AG052564, HD083614, AG045231). C.E.C. received additional funding support from the National Science Foundation (DGE-1143954) and the Mr and Mrs Spencer T. Olin Fellowship Program. D.M.D. receives additional funding from National Institute on Alcohol Abuse and Alcoholism (K02AA018755). A.R.H. receives additional funding support from NIH (R01-DA031579 and R01-AG049789). J.L.M. receives additional funding support from NIDA (K01DA037914). A.M.G. is listed as an inventor on issued U.S. Patent 8080371, ?Markers for Addiction? covering the use of certain variants in determining the diagnosis, prognosis and treatment of addiction. J.I.N. receives support as an investigator for Janssen. No other authors report biomedical financial interests or potential conflicts of interest.
Funding Information:
National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse (NIDA), Grant/Award Number: U10AA008401; National Institute on Drug Abuse, Grant/Award Numbers: DA032573, K01DA037914; NIDA; National Institutes of Health (NIH), Grant/Award Numbers: R01-AG049789, R01-DA031579, AG045231, HD083614, AG052564, DA038834, DA040716; National Science Foundation, Grant/Award Number: DGE-1143954; NIDA; Duke University; NIH, Grant/Award Numbers: AG045231, AG052564, DA038834, DA040716, HD083614, HHSN268201200008I, K02AA018755, R01-AG049789, R01-DA031579, R01-DA033369
Funding Information:
We continue to be inspired by our memories of Henri Begleiter and Theodore Reich, founding PI and Co-PI of COGA, and also owe a debt of gratitude to other past organizers of COGA, including Ting-Kai Li, P. Michael Conneally, Raymond Crowe and Wendy Reich, for their critical contributions. This national collaborative study is supported by NIH Grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA).
Funding Information:
The Duke Neurogenetics Study is supported by Duke University and the National Institutes of Health (NIH) (R01-DA033369).
Funding Information:
Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to the Johns Hopkins University, contract number HHSN268201200008I.
Publisher Copyright:
© 2019 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society
PY - 2019/7
Y1 - 2019/7
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.
KW - DSM-IV alcohol dependence criterion
KW - DSM-IV criterion count
KW - DSM-IV individual criteria
KW - alcohol dependence
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
UR - http://www.scopus.com/inward/record.url?scp=85067028100&partnerID=8YFLogxK
U2 - 10.1111/gbb.12579
DO - 10.1111/gbb.12579
M3 - Article
C2 - 31090166
AN - SCOPUS:85067028100
SN - 1601-1848
VL - 18
JO - Genes, Brain and Behavior
JF - Genes, Brain and Behavior
IS - 6
M1 - e12579
ER -