Journal article
GABRR1 and GABRR2, encoding the GABA-A receptor subunits ρ1 and ρ2, are associated with alcohol dependence
American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.153B(2), pp.418-427
03/05/2010
DOI: 10.1002/ajmg.b.30995
PMCID: PMC2829340
PMID: 19536785
Abstract
The genes encoding several GABA-A receptor subunits, including
GABRA2
, have been associated with alcoholism, suggesting that variations in GABA signaling contribute to risk. Therefore, as part of a comprehensive evaluation of the GABA receptor genes, we evaluated the potential association of
GABRR1
and
GABRR2,
which encode the ρ1 and ρ2 subunits of the pentameric GABA-A/GABA-C receptors.
GABRR1
and
GABRR2
lie in a head to tail orientation spanning 137 kb on chromosome 6q14-16. We genotyped 73 SNPs, covering both genes and extending 31 kb upstream of
GABRR2
and 95 kb downstream of
GABRR1,
in a sample of 1923 European Americans from 219 multiplex alcohol dependent families. Family-based association analyses demonstrated that SNPs in both
GABRR1
and
GABRR2
were significantly associated with alcohol dependence. Among the associated SNPs was rs282129, a coding SNP (Met430Thr) in
GABRR2
. Secondary analysis using a median split for age of onset suggests that the association is strongest when the analysis is focused upon those with earlier onset of alcohol dependence. Haplotypes in each gene were significantly overtransmitted to family members who did not meet criteria for alcohol dependence (p<0.04), and a haplotype in
GABRR2
was significantly overtransmitted to family members who met a broader definition of alcoholism (p=0.002) as well as DSM-IV dependence (p=0.04).
Details
- Title: Subtitle
- GABRR1 and GABRR2, encoding the GABA-A receptor subunits ρ1 and ρ2, are associated with alcohol dependence
- Creators
- Xiaoling Xuei - Henri Begleiter Neurodynamics Laboratory, SUNY Downstate Medical Center, Brooklyn, NYLeah Flury-Wetherill - Henri Begleiter Neurodynamics Laboratory, SUNY Downstate Medical Center, Brooklyn, NYDanielle Dick - Henri Begleiter Neurodynamics Laboratory, SUNY Downstate Medical Center, Brooklyn, NYAlison Goate - Henri Begleiter Neurodynamics Laboratory, SUNY Downstate Medical Center, Brooklyn, NYJay Tischfield - Henri Begleiter Neurodynamics Laboratory, SUNY Downstate Medical Center, Brooklyn, NYJohn Nurnberger - Henri Begleiter Neurodynamics Laboratory, SUNY Downstate Medical Center, Brooklyn, NYMarc Schuckit - Henri Begleiter Neurodynamics Laboratory, SUNY Downstate Medical Center, Brooklyn, NYJohn Kramer - Henri Begleiter Neurodynamics Laboratory, SUNY Downstate Medical Center, Brooklyn, NYSam Kuperman - Henri Begleiter Neurodynamics Laboratory, SUNY Downstate Medical Center, Brooklyn, NYVictor Hesselbrock - Henri Begleiter Neurodynamics Laboratory, SUNY Downstate Medical Center, Brooklyn, NYBernice Porjesz - Henri Begleiter Neurodynamics Laboratory, SUNY Downstate Medical Center, Brooklyn, NYTatiana Foroud - Henri Begleiter Neurodynamics Laboratory, SUNY Downstate Medical Center, Brooklyn, NYHoward J Edenberg - Henri Begleiter Neurodynamics Laboratory, SUNY Downstate Medical Center, Brooklyn, NY
- Resource Type
- Journal article
- Publication Details
- American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.153B(2), pp.418-427
- DOI
- 10.1002/ajmg.b.30995
- PMID
- 19536785
- PMCID
- PMC2829340
- NLM abbreviation
- Am J Med Genet B Neuropsychiatr Genet
- ISSN
- 1552-4841
- eISSN
- 1552-485X
- Grant note
- DOI: 10.13039/100000027, name: National Institute on Alcohol Abuse and Alcoholism (NIAAA), award: U10AA008401; DOI: 10.13039/100000026, name: National Institute on Drug Abuse (NIDA); name: Indiana Genomics Initiative of Indiana University (INGEN®); name: The Lilly Endowment, Inc.
- Language
- English
- Date published
- 03/05/2010
- Academic Unit
- Psychiatry; Stead Family Department of Pediatrics
- Record Identifier
- 9984003428602771
Metrics
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