Association of NFKB1, which encodes a subunit of the transcription factor NF-κB, with alcohol dependence

Howard J Edenberg; Xiaoling Xuei; Leah Flury Wetherill; Laura Bierut; Kathleen Bucholz; Danielle M Dick; Victor Hesselbrock; Sam Kuperman; Bernice Porjesz; Marc A Schuckit; Jay A Tischfield; Laura A Almasy; J.I Nurnberger; Tatiana Foroud

doi:10.1093/hmg/ddm368

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Association of NFKB1, which encodes a subunit of the transcription factor NF-κB, with alcohol dependence

Journal article

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Association of NFKB1, which encodes a subunit of the transcription factor NF-κB, with alcohol dependence

Howard J Edenberg, Xiaoling Xuei, Leah Flury Wetherill, Laura Bierut, Kathleen Bucholz, Danielle M Dick, Victor Hesselbrock, Sam Kuperman, Bernice Porjesz, Marc A Schuckit, …

Human molecular genetics, Vol.17(7), pp.963-970

04/01/2008

DOI: 10.1093/hmg/ddm368

PMID: 18079108

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Abstract

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-κB. NF-κB 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 ≤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.

Details

Title: Subtitle: Association of NFKB1, which encodes a subunit of the transcription factor NF-κB, with alcohol dependence
Creators: Howard J Edenberg - 1 Indiana University School of Medicine, Indianapolis, IN, USA
Xiaoling Xuei - 1 Indiana University School of Medicine, Indianapolis, IN, USA
Leah Flury Wetherill - 1 Indiana University School of Medicine, Indianapolis, IN, USA
Laura Bierut - 2 Washington University School of Medicine, St Louis, MO, USA
Kathleen Bucholz - 2 Washington University School of Medicine, St Louis, MO, USA
Danielle M Dick - 2 Washington University School of Medicine, St Louis, MO, USA
Victor Hesselbrock - 3 University of Connecticut, Farmington, CT, USA
Sam Kuperman - 4 University of Iowa Carver College of Medicine, Iowa City, IA, USA
Bernice Porjesz - 5 SUNY Health Sciences Center, Brooklyn, NY, USA
Marc A Schuckit - 6 University of California, San Diego, CA, USA
Jay A Tischfield - 7 Rutgers University, Piscataway, NJ, USA
Laura A Almasy - 8 Southwest Foundation for Biomedical Research, San Antonio, TX, USA
J.I Nurnberger - 1 Indiana University School of Medicine, Indianapolis, IN, USA
Tatiana Foroud - 1 Indiana University School of Medicine, Indianapolis, IN, USA
Resource Type: Journal article
Publication Details: Human molecular genetics, Vol.17(7), pp.963-970
Publisher: Oxford University Press
DOI: 10.1093/hmg/ddm368
PMID: 18079108
ISSN: 0964-6906
eISSN: 1460-2083
Language: English
Date published: 04/01/2008
Academic Unit: Psychiatry; Stead Family Department of Pediatrics
Record Identifier: 9984003946502771

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