GABRR1 and GABRR2, encoding the GABA-A receptor subunits rho1 and rho2, are associated with alcohol dependence.
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Author
Xuei, XiaolingFlury-Wetherill, Leah
Dick, Danielle
Goate, Alison
Tischfield, Jay
Nurnberger, John
Schuckit, Marc
Kramer, John
Kuperman, Sam
Hesselbrock, Victor
Porjesz, Bernice
Foroud, Tatiana
Edenberg, Howard J
Journal title
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric GeneticsPublication Volume
153BPublication Issue
2Publication Begin page
418Publication End page
427
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Show full item recordAbstract
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 rho1 and rho2 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 single nucleotide polymorphisms (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).Citation
Xuei X, Flury-Wetherill L, Dick D, Goate A, Tischfield J, Nurnberger J Jr, Schuckit M, Kramer J, Kuperman S, Hesselbrock V, Porjesz B, Foroud T, Edenberg HJ. GABRR1 and GABRR2, encoding the GABA-A receptor subunits rho1 and rho2, are associated with alcohol dependence. Am J Med Genet B Neuropsychiatr Genet. 2010 Mar 5;153B(2):418-427. doi: 10.1002/ajmg.b.30995. PMID: 19536785; PMCID: PMC2829340.DOI
10.1002/ajmg.b.30995ae974a485f413a2113503eed53cd6c53
10.1002/ajmg.b.30995
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