Genome-wide association studies of alcohol dependence, DSM-IV criterion count and individual criteria
dc.contributor.author | Lai, Dongbing | |
dc.contributor.author | Wetherill, Leah | |
dc.contributor.author | Bertelsen, Sarah | |
dc.contributor.author | Carey, Caitlin E. | |
dc.contributor.author | Kamarajan, Chella | |
dc.contributor.author | Kapoor, Manav | |
dc.contributor.author | Meyers, Jacquelyn L. | |
dc.contributor.author | Anokhin, Andrey P. | |
dc.contributor.author | Bennett, David A. | |
dc.contributor.author | Bucholz, Kathleen K. | |
dc.contributor.author | Chang, Katharine K. | |
dc.contributor.author | Jager, Philip L. De | |
dc.contributor.author | Dick, Danielle M. | |
dc.contributor.author | Hesselbrock, Victor | |
dc.contributor.author | Kramer, John | |
dc.contributor.author | Kuperman, Samuel | |
dc.contributor.author | Nurnberger, John I. | |
dc.contributor.author | Raj, Towfique | |
dc.contributor.author | Schuckit, Marc | |
dc.contributor.author | Scott, Denise M. | |
dc.contributor.author | Taylor, Robert E. | |
dc.contributor.author | Tischfield, Jay | |
dc.contributor.author | Hariri, Ahmad R. | |
dc.contributor.author | Edenberg, Howard J. | |
dc.contributor.author | Agrawal, Arpana | |
dc.contributor.author | Bogdan, Ryan | |
dc.contributor.author | Porjesz, Bernice | |
dc.contributor.author | Goate, Alison M. | |
dc.contributor.author | Foroud, Tatiana | |
dc.contributor.department | Medical and Molecular Genetics, School of Medicine | en_US |
dc.date.accessioned | 2021-01-25T22:56:45Z | |
dc.date.available | 2021-01-25T22:56:45Z | |
dc.date.issued | 2019-06-04 | |
dc.description.abstract | Genome-wide association studies (GWAS) of alcohol dependence (AD) have reliably identified variation within alcohol metabolizing genes (e.g., ADH1B) but have inconsistently located other signals, which may be partially attributable to symptom heterogeneity underlying the disorder. We conducted GWASs of DSM-IV AD (primary analysis), DSM-IV AD criterion count (secondary analysis), and individual dependence criteria (tertiary analysis) among 7,418 (1,121 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 3,175 (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<0.01; 0.61-1.82% of variance). Identified novel variants (i.e., rs1912461, rs61826952) were associated with differential central evoked theta power (loss minus gain; p=0.0037) and reward-related ventral striatum reactivity (p=0.008), respectively. This study suggests that studying individual criteria may unveil new insights into the genetic etiology of AD liability. | en_US |
dc.eprint.version | Author's manuscript | en_US |
dc.identifier.citation | Lai, D., Wetherill, L., Bertelsen, S., Carey, C. E., Kamarajan, C., Kapoor, M., Meyers, J. L., Anokhin, A. P., Bennett, D. A., Bucholz, K. K., Chang, K. K., Jager, P. L. D., Dick, D. M., Hesselbrock, V., Kramer, J., Kuperman, S., Nurnberger, J. I., Raj, T., Schuckit, M., … Foroud, T. (2019). Genome-wide association studies of alcohol dependence, DSM-IV criterion count and individual criteria. Genes, Brain and Behavior, 18(6), e12579. https://doi.org/10.1111/gbb.12579 | en_US |
dc.identifier.issn | 1601-183X | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/24989 | |
dc.language.iso | en_US | en_US |
dc.publisher | Wiley | en_US |
dc.relation.isversionof | https://doi.org/10.1111/gbb.12579 | en_US |
dc.relation.journal | Genes, Brain and Behavior | en_US |
dc.source | PMC | en_US |
dc.subject | alcohol dependence | en_US |
dc.subject | DSM-IV alcohol dependence criterion | en_US |
dc.subject | DSM-IV criterion count | en_US |
dc.subject | DSM-IV individual criteria | en_US |
dc.subject | item response analysis | en_US |
dc.subject | genome-wide association study | en_US |
dc.subject | meta-analysis | en_US |
dc.subject | polygenic risk score | en_US |
dc.subject | Event-Related Theta Oscillations (ERO) | en_US |
dc.subject | functional Magnetic Resonance Imaging (fMRI) | en_US |
dc.title | Genome-wide association studies of alcohol dependence, DSM-IV criterion count and individual criteria | en_US |
dc.type | Article | en_US |
Files
Original bundle
1 - 1 of 1
Loading...
- Name:
- nihms-1031511.pdf
- Size:
- 217.76 KB
- Format:
- Adobe Portable Document Format
- Description:
- Author's manuscript
License bundle
1 - 1 of 1
No Thumbnail Available
- Name:
- license.txt
- Size:
- 1.99 KB
- Format:
- Item-specific license agreed upon to submission
- Description: