Dataset Information

Markers in the 5'-region of GABRG1 associate to alcohol dependence and are in linkage disequilibrium with markers in the adjacent GABRA2 gene.

ABSTRACT: Following an initial report, there have been multiple replications of an association of alcohol dependence (AD) to markers within a haplotype block that includes the 3'-half of the gene encoding the GABA(A) alpha-2 subunit (GABRA2), on chromosome 4p. We examined the intergenic extent of this haplotype block and the association to AD of markers in the adjacent 5' haplotype block in GABRG1, which encodes the GABA(A) receptor gamma-1 subunit. We genotyped 15 single nucleotide polymorphisms in the GABRG1-GABRA2 interval as well as at 34 ancestry informative markers in three samples: 435 AD and 635 screened control subjects from Connecticut and 812 participants from a multicenter AD treatment trial. We observed two large haplotype blocks in the GABRG1-GABRA2 intergenic interval with a region of increased recombination midway between the two genes. Markers in the two haplotype blocks were in moderate linkage disequilibrium. Compared with markers in the GABRA2 haplotype block, markers in the 5' GABRG1 haplotype showed greater allelic, genotypic and haplotypic association with AD in European Americans from both AD samples. Logistic regression analysis indicated that genetic elements in the GABRG1 haplotype block likely contribute to AD risk in an additive manner, whereas those in the GABRA2 haplotype block may act in a dominant manner in relation to risk of AD.

SUBMITTER: Covault J

PROVIDER: S-EPMC2743531 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature

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Markers in the 5'-region of GABRG1 associate to alcohol dependence and are in linkage disequilibrium with markers in the adjacent GABRA2 gene.

Covault Jonathan J Gelernter Joel J Jensen Kevin K Anton Raymond R Kranzler Henry R HR

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20070516 4

Following an initial report, there have been multiple replications of an association of alcohol dependence (AD) to markers within a haplotype block that includes the 3'-half of the gene encoding the GABA(A) alpha-2 subunit (GABRA2), on chromosome 4p. We examined the intergenic extent of this haplotype block and the association to AD of markers in the adjacent 5' haplotype block in GABRG1, which encodes the GABA(A) receptor gamma-1 subunit. We genotyped 15 single nucleotide polymorphisms in the G ...[more]

PMID: 17507911

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Project description:Mapping by admixture linkage disequilibrium (MALD) is a potentially powerful technique for the mapping of complex genetic diseases. The practical requirements of this method include (a) a set of markers spanning the genome that have large allele-frequency differences between the parental ethnicities contributing to the admixed population and (b) an understanding of the extent of admixture in the study population. To this end, a DNA-pooling technique was used to screen microsatellite and diallelic insertion/deletion markers for allele-frequency differences between putative representatives of the parental populations of the admixed Mexican American (MA) and African American (AA) populations. Markers with promising pooled differences were then confirmed by individual genotyping in both the parental and admixed populations. For the MA population, screening of >600 markers identified 151 ethnic-difference markers (EDMs) with delta>0.30 (where delta is the absolute value of each allele-frequency difference between two populations, summed over all marker alleles and divided by two) that are likely to be useful for MALD analysis. For the AA population, analysis of >400 markers identified 97 EDMs. In addition, individual genotyping of these markers in Pima Amerindians, Yavapai Amerindians, European American (EA) individuals, Africans from Zimbabwe, MA individuals, and AA individuals, as well as comparison to the CEPH genotyping set, suggests that the differences between subpopulations of an ethnicity are small for many markers with large interethnic differences. Estimates of admixture that are based on individual genotyping of these markers are consistent with a 60% EA:40% Amerindian contribution to MA populations and with a 20% EA:80% African contribution to AA populations. Taken together, these data suggest that EDMs with large interpopulation and small intrapopulation differences can be readily identified for MALD studies in both AA and MA populations.

Dataset Information

Markers in the 5'-region of GABRG1 associate to alcohol dependence and are in linkage disequilibrium with markers in the adjacent GABRA2 gene.

Publications

Markers in the 5'-region of GABRG1 associate to alcohol dependence and are in linkage disequilibrium with markers in the adjacent GABRA2 gene.

Similar Datasets

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