Association of NFKB1, which encodes a subunit of the transcription factor NF- B, with alcohol dependence
Open accessAbstract
A broad region on chromosome 4q has been linked to alcohol dependence (alcoholism). We hypothesized that such broad linkage regions represent the combined action of multiple genes. Seeking to identify genes within that region that are associated with alcoholism, we have tested the association of NFKB1, located at 4q24, with alcoholism. NFKB1 encodes a 105 kDa transcription inhibitor that is cleaved to the 50 kDa DNA-binding subunit of the ubiquitous transcription factor NF-kappaB. NF-kappaB regulates many genes relevant to brain function, and its actions can be potentiated by ethanol; thus, NFKB1 is an excellent candidate gene for alcoholism. Nineteen SNPs in and near NFKB1 were analyzed in a sample of 219 multiplex alcoholic families of European American descent. Family-based association analyses detected significant evidence of association with eight SNPs and marginal evidence for five more. The association was driven by the affected individuals with earlier onset of alcoholism (55% of the sample with onset < or =21 years). Further analysis of the age of onset as a quantitative variable provided evidence for the association of 12 SNPs in this gene. Thus, variations in NFKB1 appear to affect the risk for alcoholism, particularly contributing to an earlier onset of the disease.
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Human genetic variations in NF-κB genes are associated with increased risk for alcoholism, particularly early onset.
“Human genetic variations in NF-κB genes have been associated with increased risk for human alcoholism, particularly early onset alcoholism (Edenberg et al., 2008).”
From Impulsivity, frontal lobes and risk for addiction (2009) · cites this paper as Edenberg et al., 2008
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“Human genetic variations in NF-κB genes have been associated with increased risk for human alcoholism, particularly early onset alcoholism (Edenberg et al., 2008).”
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- Authors
- Edenberg, H. J., Xuei, X., Wetherill, L. F., Bierut, L., Bucholz, K., Dick, D. M., Hesselbrock, V., Kuperman, S., Porjesz, B., Schuckit, M. A., Tischfield, J. A., Almasy, L. A., Nurnberger, J. I., & Foroud, T.
- Affiliations
- Indiana University School of Medicine (US)
- Washington University in St. Louis (US)
- University of Connecticut (US)
- University of California San Diego (US)
- Rutgers, The State University of New Jersey (US)
- Texas Biomedical Research Institute (US)
- Corresponding author
- Edenberg, H. J.
- ORCID
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-12-07
- Volume
- 17
- Issue
- 7
- Pages
- 963-970
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2141160897
- Cited by
- 89
- References
- 80
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 5 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 6 · 2017: 3 · 2016: 7 · 2015: 2 · 2014: 10 · 2013: 8 · 2012: 11
- FWCI
- 3.57
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Human Molecular Genetics (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Eli Lilly and Company
- Lilly Endowment
- State University of New York
- Washington University in St. Louis
- University of Connecticut
- National Institutes of Health
- SUNY Downstate Medical Center
- School of Medicine, Indiana University
- National Institute on Alcohol Abuse and Alcoholism (U10AA008401)
- National Institute on Drug Abuse
- 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
- NFKB1, NF-κB, alcoholism, candidate genes, single nucleotide polymorphisms, family-based association, age of onset, European Americans, genetic susceptibility
- MeSH terms
- Alcoholism, Chromosomes, Human, Pair 4, Exons, Humans, Introns, Transcription Factors, United States, Linkage Disequilibrium, NF-kappa B, Age of Onset, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, White People, NF-kappa B p50 Subunit
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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