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Genome‐Wide Association Study of Alcohol Dependence Implicates a Region on Chromosome 11
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Background: Alcohol dependence is a complex disease, and although linkage and candidate gene studies have identified several genes associated with the risk for alcoholism, these explain only a portion of the risk. Methods: We carried out a genome‐wide association study (GWAS) on a case–control sample drawn from the families in the Collaborative Study on the Genetics of Alcoholism. The cases all met diagnostic criteria for alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders–Fourth Edition; controls all consumed alcohol but were not dependent on alcohol or illicit drugs. To prioritize among the strongest candidates, we genotyped most of the top 199 single nucleotide polymorphisms (SNPs) (p ≤ 2.1 × 10−4) in a sample of alcohol‐dependent families and performed pedigree‐based association analysis. We also examined whether the genes harboring the top SNPs were expressed in human brain or were differentially expressed in the presence of ethanol in lymphoblastoid cells. Results: Although no single SNP met genome‐wide criteria for significance, there were several clusters of SNPs that provided mutual support. Combining evidence from the case–control study, the follow‐up in families, and gene expression provided strongest support for the association of a cluster of genes on chromosome 11 (SLC22A18, PHLDA2, NAP1L4, SNORA54, CARS, and OSBPL5) with alcohol dependence. Several SNPs nominated as candidates in earlier GWAS studies replicated in ours, including CPE, DNASE2B, SLC10A2, ARL6IP5, ID4, GATA4, SYNE1, and ADCY3. Conclusions: We have identified several promising associations that warrant further examination in independent samples.
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For ALC, the published GWAS are small and no large-scale meta-analysis has been conducted.
“For ALC, the published GWAS are small and no large-scale meta-analysis has been conducted. 93–97”
From Genetic architectures of psychiatric disorders: the emerging picture and its implications (2012) · cites this paper as [94]
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Polygenic Scores for Major Depressive Disorder and Risk of Alcohol Dependence
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“Several GWAS of AD have © 2015 Society for the Study of Addiction Addiction Biology, 22, 535–549 been performed, detecting different risk loci (Bierut et al. 2010; Edenberg et al. 2010; Zuo et al. 2012; Gelernter et al. 2014; Quillen et al. 2014).”
Background
Metadata
- Authors
- Edenberg, H. J., Koller, D. L., Xuei, X., Wetherill, L., McClintick, J. N., Almasy, L., Bierut, L. J., Bucholz, K. K., Goate, A., Aliev, F., Dick, D., Hesselbrock, V., Hinrichs, A., Kramer, J., Kuperman, S., Nurnberger, J. I., Rice, J. P., Schuckit, M. A., Taylor, R., Todd Webb, B., Tischfield, J. A., Porjesz, B., & Foroud, T.
- Affiliations
- Indiana University School of Medicine (US)
- University of Iowa (US)
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Edenberg, Howard J.
- ORCID
- Venue
- Alcoholism: Clinical and Experimental Research
- Publisher
- Wiley
- Published
- 2010-04-23
- Volume
- 34
- Issue
- 5
- Pages
- 840-852
- ISSN
- 0145-6008 (ISSN-L)
- 1530-0277
- PMC
- PMC2884073
- OpenAlex
- W1547613518
- Cited by
- 293
- References
- 73
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 5 · 2023: 7 · 2022: 7 · 2021: 7 · 2020: 8 · 2019: 12 · 2018: 16 · 2017: 23 · 2016: 23 · 2015: 29 · 2014: 29 · 2013: 38 · 2012: 38
- FWCI
- 21.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alcoholism Clinical and Experimental Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- SUNY Digital Repository Support (State University of New York System) (submittedVersion, cc-by-nc-nd)
- IUScholarWorks (Indiana University) (submittedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (K02AA018755, R01AA012725, R24AA012725, R28AA012725, U10AA008401)
- National Human Genome Research Institute (U01HG004438, HHSN268200782096C)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- alcoholism, alcoholism genetics, chromosome 11, single nucleotide polymorphisms, Collaborative Study on the Genetics of Alcoholism, SLC22A18, PHLDA2, candidate genes
- MeSH terms
- Adolescent, Adult, Alcoholism, Chromosomes, Human, Pair 11, Female, Follow-Up Studies, Gene Expression Regulation, Humans, Male, Middle Aged, Case-Control Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Gene Expression Profiling, Genome-Wide Association Study, Young Adult
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