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Selected SNPs (selected + snp)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Association of psoriasis to PGLYRP and SPRR genes at PSORS4 locus on 1q shows heterogeneity between Finnish, Swedish and Irish families

EXPERIMENTAL DERMATOLOGY, Issue 2 2009
Kati Kainu
Abstract:, A susceptibility locus for psoriasis, PSORS4, has been mapped to chromosome 1q21 in the region of the epidermal differentiation complex. The region has been refined to a 115 kb interval around the loricrin (LOR) gene. However, no evidence of association between polymorphisms in the LOR gene and psoriasis has been found. Therefore, we have analysed association to three candidate gene clusters of the region, the S100, small proline-rich protein (SPRR) and PGLYRP (peptidoglycan recognition protein) genes, which all contain functionally interesting psoriasis candidate genes. In previous studies, the SPRR and S100 genes have shown altered expression in psoriasis. Also polymorphisms in the PGLYRP genes have shown to be associated with psoriasis. We genotyped altogether 29 single nucleotide polymorphisms (SNPs) in 255 Finnish psoriasis families and analysed association with psoriasis using transmission disequilibrium test. A five-SNP haplotype of PGLYRP SNPs associated significantly with psoriasis. There was also suggestive evidence of association to SPRR gene locus in Finnish families. To confirm the putative associations, selected SNPs were genotyped also in a family collection of Swedish and Irish patients. The families supported association to the two gene regions, but there was also evidence of allelic heterogeneity. [source]

GABRA2 and Alcohol Use Disorders: No Evidence of an Association in an Italian Case,Control Study

ALCOHOLISM, Issue 4 2010
Nicoletta Onori
Background:, Alcoholism is a major health and social issue, a highly frequent disease and a cause of premature death. It is also the most expensive addictive disorder being related to high morbidity and mortality, violence, accidents, and social and legal problems. It is a quantitative disorder, where the combined incidence of environmental and multiple genetic factors varies from 1 subject to another. Recent association studies have identified several genes as candidates for alcoholism, including GABAA receptor genes, due to their role in mediating several behavioral effects of alcohol, such as motor incoordination, anxiolysis, sedation, and withdrawal. The proposed association between the 3, half of the gene encoding the alpha-2 subunit of GABA receptor (3,-GABRA2) and alcohol use disorders (AUDs) has received several independent confirmations. Methods:, In this study, 10 single nucleotide polymorphisms (SNPs) of the 3,-GABRA2 gene, previously reported to be implicated in alcohol dependence, were used to evaluate the linkage between selected SNPs and AUDs in an Italian sample and to compare findings with those of previous studies. Results:, No evidence of an association was found at the allele, genotype, haplotype, or diplotype levels between the 3,-GABRA2 polymorphisms investigated and alcoholism in 149 Italian alcoholics (98 alcohol dependents and 51 alcohol abusers) and 278 controls. Conclusions:, Despite previous reports, we did not find an association between AUDs and 3,-GABRA2 polymorphisms. This is probably due to the minimal comorbidity of our Italian sample suggesting that this gene is implicated in polysubstance dependence rather than in alcoholism alone. [source]

SNP Selection for Association Studies: Maximizing Power across SNP Choice and Study Size

ANNALS OF HUMAN GENETICS, Issue 6 2005
F. Pardi
Summary Selection of single nucleotide polymorphisms (SNPs) is a problem of primary importance in association studies and several approaches have been proposed. However, none provides a satisfying answer to the problem of how many SNPs should be selected, and how this should depend on the pattern of linkage disequilibrium (LD) in the region under consideration. Moreover, SNP selection is usually considered as independent from deciding the sample size of the study. However, when resources are limited there is a tradeoff between the study size and the number of SNPs to genotype. We show that tuning the SNP density to the LD pattern can be achieved by looking for the best solution to this tradeoff. Our approach consists of formulating SNP selection as an optimization problem: the objective is to maximize the power of the final association study, whilst keeping the total costs below a given budget. We also propose two alternative algorithms for the solution of this optimization problem: a genetic algorithm and a hill climbing search. These standard techniques efficiently find good solutions, even when the number of possible SNPs to choose from is large. We compare the performance of these two algorithms on different chromosomal regions and show that, as expected, the selected SNPs reflect the LD pattern: the optimal SNP density varies dramatically between chromosomal regions. [source]

Contribution of a haplotype in the HLA region to anti,cyclic citrullinated peptide antibody positivity in rheumatoid arthritis, independently of HLA,DRB1

ARTHRITIS & RHEUMATISM, Issue 12 2009
Yukinori Okada
Objective To examine the risk of anti,cyclic citrullinated peptide (anti-CCP) antibody positivity in rheumatoid arthritis (RA) patients carrying certain haplotypes in the HLA region. Methods A total of 1,389 Japanese patients with RA were genotyped for 30 single-nucleotide polymorphisms (SNPs) in the HLA region using commercial oligonucleotide arrays (from Perlegen or Affymetrix) as well as for HLA,DRB1 alleles using a sequence-specific polymerase chain reaction method. Stepwise logistic regression was used to select from among the 30 SNPs the ones that represented a risk of anti-CCP antibody positivity. Haplotypes of the selected SNPs were inferred using an expectation-maximization algorithm. Associations of individual SNPs were evaluated with the Cochran-Armitage test for trend. DRB1 alleles and haplotypes were evaluated with the chi-square test. Heterogeneities of risks among the shared epitope (SE) and non-SE HLA,DRB1 alleles were examined using the exact test. Haplotype associations that were independent of individual HLA,DRB1 alleles were evaluated using the likelihood ratio test. Results Significant associations were found for 9 SNPs (smallest P value being 2.4 × 10,8) and in 4 HLA,DRB1 alleles (smallest P value being 2.0 × 10,10 in DRB1*0405). Stepwise logistic regression selected 4 SNPs (rs9262638, rs7775228, rs4713580, and rs9277359). Among the 16 inferred haplotypes of these 4 SNPs, 6 indicated significant associations (smallest P value being 1.9 × 10,11). Risks among SE and non-SE alleles were significantly heterogeneous (P = 0.0095 and P = 9.8 × 10,9, respectively), indicating the importance of stratification with individual DRB1 alleles rather than SE alleles. Conditional analysis of the risk associated with individual DRB1 alleles identified a risk haplotype that was independent of DRB1 (odds ratio 2.00 [95% confidence interval 1.44,2.79], P = 2.6 × 10,5). Conclusion Heterogeneous risks of anti-CCP antibody positivity were confirmed among SE and non-SE alleles in our patient population. A risk haplotype in the HLA region that is independent of HLA,DRB1 was confirmed. [source]