The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Genome-wide association study of alcohol dependence:significant findings in African- and European-Americans including novel risk loci
Open accessAbstract
We report a GWAS of alcohol dependence (AD) in European-American (EA) and African-American (AA) populations, with replication in independent samples of EAs, AAs and Germans. Our sample for discovery and replication was 16 087 subjects, the largest sample for AD GWAS to date. Numerous genome-wide significant (GWS) associations were identified, many novel. Most associations were population specific, but in several cases were GWS in EAs and AAs for different SNPs at the same locus,showing biological convergence across populations. We confirmed well-known risk loci mapped to alcohol-metabolizing enzyme genes, notably ADH1B (EAs: Arg48His, P=1.17 × 10−31; AAs: Arg369Cys, P=6.33 × 10−17) and ADH1C in AAs (Thr151Thr, P=4.94 × 10−10), and identified novel risk loci mapping to the ADH gene cluster on chromosome 4 and extending centromerically beyond it to include GWS associations at LOC100507053 in AAs (P=2.63 × 10−11), PDLIM5 in EAs (P=2.01 × 10−8), and METAP in AAs (P=3.35 × 10−8). We also identified a novel GWS association (1.17 × 10−10) mapped to chromosome 2 at rs1437396, between MTIF2 and CCDC88A, across all of the EA and AA cohorts, with supportive gene expression evidence, and population-specific GWS for markers on chromosomes 5, 9 and 19. Several of the novel associations implicate direct involvement of, or interaction with, genes previously identified as schizophrenia risk loci. Confirmation of known AD risk loci supports the overall validity of the study; the novel loci are worthy of genetic and biological follow-up. The findings support a convergence of risk genes (but not necessarily risk alleles) between populations, and, to a lesser extent, between psychiatric traits.
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Cites
Principal components analysis corrects for stratification in genome-wide association studies
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A variant associated with nicotine dependence, lung cancer and peripheral arterial disease
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Genome‐wide significant association between alcohol dependence and a variant in the ADH gene cluster
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Self-citationLi, D., Zhao, H., & Gelernter, J. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.02.024 · Cited by 165
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23andMe Research Team, Walters, R. K., Polimanti, R., Johnson, E. C., McClintick, J. N., Adams, M. J., Adkins, A. E., Aliev, F., Bacanu, S.-A., Batzler, A., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0275-1 · Cited by 632
Self-citationClarke, T.-K., Adams, M. J., Davies, G., Howard, D. M., Hall, L. S., Padmanabhan, S., Murray, A. D., Smith, B. H., Campbell, A., Hayward, C., et al. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.153 · Cited by 440
Sanchez-Roige, S., Palmer, A. A., Fontanillas, P., Elson, S. L., the 23andMe Research Team, T. S. U. D. W. G. O. T. P. G. C., Adams, M. J., Howard, D. M., Edenberg, H. J., Davies, G., Crist, R. C., et al. (2019) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2018.18040369 · Cited by 430
Fast Principal-Component Analysis Reveals Convergent Evolution of ADH1B in Europe and East Asia
Galinsky, K. J., Bhatia, G., Loh, P.-R., Georgiev, S., Mukherjee, S., Patterson, N. J., & Price, A. L. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.12.022 · Cited by 371
Zhou, H., Sealock, J. M., Sanchez-Roige, S., Clarke, T.-K., Levey, D. F., Cheng, Z., Li, B., Polimanti, R., Kember, R. L., Smith, R. V., et al. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-0643-5 · Cited by 359
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Metadata
- Authors
- Gelernter, J., Kranzler, H. R., Sherva, R., Almasy, L., Koesterer, R., Smith, A. H., Anton, R., Preuss, U. W., Ridinger, M., Rujescu, D., Wodarz, N., Zill, P., Zhao, H., & Farrer, L. A.
- Venue
- Molecular Psychiatry
- Published
- 2013-10-29
- Volume
- 19
- Issue
- 1
- Pages
- 41-49
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2147425235
- Cited by
- 370
- References
- 10
- FWCI
- 23.47
- Type
- journal article
- Language
- en
- Open access
- green
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