GABRR1 and GABRR2, encoding the GABA-A receptor subunits rho1 and rho2, are associated with alcohol dependence.

paper Primary Public

Authors: Xuei, Xiaoling; Flury-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
Year: 2010
Journal: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
PMID: 19536785
DOI: 10.1002/ajmg.b.30995
PMCID: PMC2829340

#	Section	Preview
0	Introduction	Alcoholism is a complex genetic disorder, affected by multiple genes, environmental and social…
1	Introduction	GABA-A receptors are ligand-gated anion channels formed by pentameric complexes including α, β,…
2	Introduction	GABA-A family of receptors, and they form ligand-gated chloride channels, but insensitivity of the…
3	Introduction	Several GABA receptor genes are associated with alcoholism. The association of GABRA2 with…
4	Introduction	this subgroup is characterized by greater severity of alcohol problems (Dick et al., 2007). SNPs in…
5	Introduction	There is evidence for linkage of the power in the gamma band (29-45 Hz) of the resting…
6	Introduction	concentration (400 nM) of GABA (Mihic and Harris, 1996). Two amino acids in the GABA-A receptor…
7	Introduction	Therefore, we examined whether GABRR1 and GABRR2 might be associated with alcoholism. We genotyped…
8	Materials and Methods — Subjects	Subjects were collected at six centers in the United States: Indiana University, State University of…
9	Materials and Methods — SNP genotyping	Because HapMap data indicated that flanking genes were in LD with the GABRR1-GABRR2 gene cluster, we…
10	Materials and Methods — SNP genotyping	Most assays were designed for the Sequenom MassArray system (Sequenom, San Diego, CA) using…
11	Materials and Methods — SNP genotyping	All SNPs were tested for Mendelian inheritance using the program PEDCHECK (O’Connell and Weeks,…
12	Materials and Methods — Statistical analyses	Linkage disequilibrium among genotyped SNPs was evaluated using HAPLOVIEW (Barrett et al., 2005).…
13	Materials and Methods — Statistical analyses	Family based association analyses were performed using the Pedigree Disequilibrium test (PDT)…
14	Materials and Methods — Statistical analyses	For our primary phenotype, we employed the DSM-IV criteria for alcohol dependence (American…
15	Materials and Methods — Statistical analyses	We performed secondary analyses exploring the hypothesis that genetic effects are stronger in those…
16	Results	GABRR1 and GABRR2 are in a head-to-tail orientation spanning 137 kb on chromosome 6q (Figure 1).…
17	Results	SNP coverage was further assessed using Tagger (de Bakker et al., 2005); 61 of the SNPs were…
18	Results	Six SNPs were significantly associated with alcohol dependence defined by DSM-IV criteria (p < 0.05)…
19	Results	We have previously found that the associations of GABRA2, CHRM2, and NFKB1 with alcoholism were…

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