Genomewide Association Analysis of Symptoms of Alcohol Dependence in the Molecular Genetics of Schizophrenia (MGS2) Control Sample: SYMPTOMS OF AD IN THE MGS2 CONTROL SAMPLE
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BACKGROUND: While genetic influences on alcohol dependence (AD) are substantial, progress in the identification of individual genetic variants that impact on risk has been difficult. METHODS: We performed a genome-wide association study on 3,169 alcohol consuming subjects from the population-based Molecular Genetics of Schizophrenia (MGS2) control sample. Subjects were asked 7 questions about symptoms of AD which were analyzed by confirmatory factor analysis. Genotyping was performed using the Affymetrix 6.0 array. Three sets of analyses were conducted separately for European American (EA, n = 2,357) and African-American (AA, n = 812) subjects: individual single nucleotide polymorphisms (SNPs), candidate genes and enriched pathways using gene ontology (GO) categories. RESULTS: The symptoms of AD formed a highly coherent single factor. No SNP approached genome-wide significance. In the EA sample, the most significant intragenic SNP was in KCNMA1, the human homolog of the slo-1 gene in C. Elegans. Genes with clusters of significant SNPs included AKAP9, phosphatidylinositol glycan anchor biosynthesis, class G (PIGG), and KCNMA1. In the AA sample, the most significant intragenic SNP was CEACAM6 and genes showing empirically significant SNPs included KCNQ5, SLC35B4, and MGLL. In the candidate gene based analyses, the most significant findings were with ADH1C, nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NFKB1) and ankyrin repeat and kinase domain containing 1 (ANKK1) in the EA sample, and ADH5, POMC, and CHRM2 in the AA sample. The ALIGATOR program identified a significant excess of associated SNPs within and near genes in a substantial number of GO categories over a range of statistical stringencies in both the EA and AA sample. CONCLUSIONS: While we cannot be highly confident about any single result from these analyses, a number of findings were suggestive and worthy of follow-up. Although quite large samples will be needed to obtain requisite power, the study of AD symptoms in general population samples is a viable complement to case-control studies in identifying genetic risk variants for AD.
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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 [96]
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Genetic architectures of psychiatric disorders: the emerging picture and its implications
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Recent advances in the genetic epidemiology and molecular genetics of substance use disorders
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Self-citationGenes encoding enzymes involved in ethanol metabolism
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Stress–response pathways are altered in the hippocampus of chronic alcoholics
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- Authors
- Kendler, K. S., Kalsi, G., Holmans, P. A., Sanders, A. R., Aggen, S. H., Dick, D. M., Aliev, F., Shi, J., Levinson, D. F., & Gejman, P. V.
- Affiliations
- Virginia Commonwealth University (US)
- Endeavor Health (US)
- Corresponding author
- Kendler, Kenneth S.
- ORCID
- Venue
- Alcoholism: Clinical and Experimental Research
- Publisher
- Wiley
- Published
- 2011-02-11
- Volume
- 35
- Issue
- 5
- Pages
- 963-975
- ISSN
- 0145-6008 (ISSN-L)
- PMC
- PMC3083473
- OpenAlex
- W1954226798
- Cited by
- 121
- References
- 97
- Citations by year
- 2024: 1 · 2023: 4 · 2022: 2 · 2021: 4 · 2020: 7 · 2019: 6 · 2018: 10 · 2017: 17 · 2016: 6 · 2015: 9 · 2014: 23 · 2013: 13 · 2012: 16
- FWCI
- 10.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Alcoholism Clinical and Experimental Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Emory University
- Louisiana State University
- NorthShore University HealthSystem
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (K02AA018755, R37AA011408, P30AA019372, P20AA017828, R01AA011408)
- National Institute of Mental Health (R01 MH61675, U01-MH79470, R01 MH-59571, R01MH59588, R01-MH59566, R01-MH60879, R01-MH60870, R01-MH59586, R01MH059566, R01 MH81800, R01MH59587, R01-MH59565, R01MH059571, R01MH060879, R01MH059565, R01MH081800, R01 MH-67257, R01MH060870, U01MH079469, R01MH061675, R01MH059586, R01MH059588, R01MH067257, U01MH079470, R01MH059587, U01MH-79469)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- alcoholism, alcohol dependence symptoms, genetic risk variants, single nucleotide polymorphisms, KCNMA1, KCNQ5, ANKK1, ADH1C, ADH5, proopiomelanocortin, M2 muscarinic receptor, NFKB1, CEACAM6, monoglyceride lipase, African Americans, European Americans, gene ontology pathways, alcohol consumption
- MeSH terms
- Alcoholism, Female, Genotype, Humans, Male, Population Surveillance, Random Allocation, Schizophrenia, Polymorphism, Single Nucleotide, Genome-Wide Association Study
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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