No evidence for association with Parkinson disease for 13 single-nucleotide polymorphisms identified by whole-genome association screening.
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ABSTRACT:
SUBMITTER: Goris A
PROVIDER: S-EPMC1474094 | biostudies-literature | 2006 Jun
REPOSITORIES: biostudies-literature
Publications
No evidence for association with Parkinson disease for 13 single-nucleotide polymorphisms identified by whole-genome association screening.
Goris A A Williams-Gray C H CH Foltynie T T Compston D A S DA Barker R A RA Sawcer S J SJ
American journal of human genetics 20060601 6
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Project description:ContextThe human tau gene, which promotes assembly of neuronal microtubules, has been associated with several rare neurologic diseases that clinically include parkinsonian features. We recently observed linkage in idiopathic Parkinson disease (PD) to a region on chromosome 17q21 that contains the tau gene. These factors make tau a good candidate for investigation as a susceptibility gene for idiopathic PD, the most common form of the disease.ObjectiveTo investigate whether the tau gene is involved in idiopathic PD.Design, setting, and participantsAmong a sample of 1056 individuals from 235 families selected from 13 clinical centers in the United States and Australia and from a family ascertainment core center, we tested 5 single-nucleotide polymorphisms (SNPs) within the tau gene for association with PD, using family-based tests of association. Both affected (n = 426) and unaffected (n = 579) family members were included; 51 individuals had unclear PD status. Analyses were conducted to test individual SNPs and SNP haplotypes within the tau gene.Main outcome measureFamily-based tests of association, calculated using asymptotic distributions.ResultsAnalysis of association between the SNPs and PD yielded significant evidence of association for 3 of the 5 SNPs tested: SNP 3, P =.03; SNP 9i, P =.04; and SNP 11, P =.04. The 2 other SNPs did not show evidence of significant association (SNP 9ii, P =.11, and SNP 9iii, P =.87). Strong evidence of association was found with haplotype analysis, with a positive association with one haplotype (P =.009) and a negative association with another haplotype (P =.007). Substantial linkage disequilibrium (P<.001) was detected between 4 of the 5 SNPs (SNPs 3, 9i, 9ii, and 11).ConclusionsThis integrated approach of genetic linkage and positional association analyses implicates tau as a susceptibility gene for idiopathic PD.
| S-EPMC3973175 | biostudies-literature
Project description:Bipolar disorder (BD) is a complex disorder with a number of susceptibility genes and environmental risk factors involved in its pathogenesis. In recent years, huge progress has been made in molecular techniques for genetic studies, which have enabled identification of numerous genomic regions and genetic variants implicated in BD across populations. Despite the abundance of genetic findings, the results have often been inconsistent and not replicated for many candidate genes/single nucleotide polymorphisms (SNPs). Therefore, the aim of the review presented here is to summarize the most important data reported so far in candidate gene and genome-wide association studies. Taking into account the abundance of association data, this review focuses on the most extensively studied genes and polymorphisms reported so far for BD to present the most promising genomic regions/SNPs involved in BD. The review of association data reveals evidence for several genes (SLC6A4/5-HTT [serotonin transporter gene], BDNF [brain-derived neurotrophic factor], DAOA [D-amino acid oxidase activator], DTNBP1 [dysbindin], NRG1 [neuregulin 1], DISC1 [disrupted in schizophrenia 1]) to be crucial candidates in BD, whereas numerous genome-wide association studies conducted in BD indicate polymorphisms in two genes (CACNA1C [calcium channel, voltage-dependent, L type, alpha 1C subunit], ANK3 [ankyrin 3]) replicated for association with BD in most of these studies. Nevertheless, further studies focusing on interactions between multiple candidate genes/SNPs, as well as systems biology and pathway analyses are necessary to integrate and improve the way we analyze the currently available association data.
| S-EPMC3798233 | biostudies-literature
Project description:BackgroundA promising application of the huge amounts of genetic data currently available lies in developing a better understanding of complex diseases, such as cancer. Analysis of publicly available databases can help identify potential candidates for genes or mutations specifically related to the cancer phenotype. In spite of their huge potential to affect gene function, no systematic attention has been paid so far to the changes that occur in untranslated regions of mRNA.ResultsIn this study, we used Expressed Sequence Tag (EST) databases as a source for cancer-related sequence polymorphism discovery at the whole-genome level. Using a novel computational procedure, we focused on the identification of untranslated region (UTR)-localized non-coding Single Nucleotide Polymorphisms (UTR-SNPs) significantly associated with the tumoral state. To explore possible relationships between genetic mutation and phenotypic variation, bioinformatic tools were used to predict the potential impact of cancer-associated UTR-SNPs on mRNA secondary structure and UTR regulatory elements. We provide a comprehensive and unbiased description of cancer-associated UTR-SNPs that may be useful to define genotypic markers or to propose polymorphisms that can act to alter gene expression levels. Our results suggest that a fraction of cancer-associated UTR-SNPs may have functional consequences on mRNA stability and/or expression.ConclusionWe have undertaken a comprehensive effort to identify cancer-associated polymorphisms in untranslated regions of mRNA and to characterize putative functional UTR-SNPs. Alteration of translational control can change the expression of genes in tumor cells, causing an increase or decrease in the concentration of specific proteins. Through the description of testable candidates and the experimental validation of a number of UTR-SNPs discovered on the secreted protein acidic and rich in cysteine (SPARC) gene, this report illustrates the utility of a cross-talk between in silico transcriptomics and cancer genetics.
| S-EPMC1774567 | biostudies-literature
Project description:Genetic susceptibility is involved in the pathogenesis of vitiligo. Association studies with a whole genome-based approach instead of a single or a few candidate genes may be useful for discovering new susceptible genes. Although the etiology of non-segmental and segmental types is different, the association between gene polymorphisms and vitiligo has been reported, without defining types or in non-segmental type. Whole genome-based single nucleotide polymorphisms (SNPs) were examined in patients with non-segmental and segmental types of vitiligo using the Affymetrix GeneChip 500K mapping array, and 10 functional classes of significant SNPs were selected. Genotyping and data analysis of selected 10 SNPs was performed using real-time PCR. Genotype and allele frequencies were significantly different between both types of vitiligo and three of the target SNPs, DNAH5 (rs2277046), STRN3 (rs2273171), and KIAA1005 (rs3213758). A stronger association was suggested between the mutation in KIAA1005 (rs3213758) and the segmental type compared to the non-segmental type of vitiligo. DNAH5 (rs2277046), STRN3 (rs2273171), and KIAA1005 (rs3213758) may be new vitiligo-related SNPs in Korean patients, either non-segmental or segmental type.
| S-EPMC3653093 | biostudies-literature
Project description: Not available
| S-EPMC1474092 | biostudies-literature
Project description:Psoriasis is an immune-mediated chronic and painful disease characterized by red raised patches of inflamed skin that may have desquamation, silvery-white scales, itching and cracks. The susceptibility of developing psoriasis depends on multiple factors, with a complex interplay between genetic and environmental factors. Studies have suggested an association between autosomal dominant CARD14 (caspase recruitment domain-containing protein 14) gain-of-function mutations with the pathophysiology of psoriasis. In this study, non-synonymous single-nucleotide polymorphisms (nsSNPs) of CARD14 gene were assessed to determine their association with psoriasis in Pakistani population. A total of 123 subjects (63 patients with psoriasis and 60 normal controls) were included in this study. DNA was extracted from blood, and PCR analysis was performed followed by Sanger sequencing for 18 CARD14 specific nsSNPs (14 previously reported and the 4 most pathogenic nsSNPs identified using bioinformatics analysis). Among the 18 tested SNPs, only 2 nsSNP, rs2066965 (R547S) and rs34367357 (V585I), were found to be associated with psoriasis. Furthermore, rs2066965 heterozygous genotype was found to be more prevalent in patients with joint pain. Additionally, the 3D structure of CARD14 protein was predicted using alpha-fold2. NMSim web server was used to perform coarse grind simulations of wild-type CARD14 and two mutated structures. R547S increases protein flexibility, whereas V353I is shown to promote CARD14-induced NF-kappa B activation. This study confirms the association between two CARD14 nsSNPs, rs2066965 and rs34367357 with psoriasis in a Pakistani population, and could be helpful in identifying the role of CARD14 gene variants as potential genetic markers in patients with psoriasis.
| S-EPMC9409305 | biostudies-literature
Project description:Several whole-genome association studies have reported identification of type 2 diabetes susceptibility genes in various European-derived study populations. Little investigation of these loci has been reported in other ethnic groups, specifically African Americans. Striking differences exist between these populations, suggesting they may not share identical genetic risk factors. Our objective was to examine the influence of type 2 diabetes genes identified in whole-genome association studies in a large African American case-control population.Single nucleotide polymorphisms (SNPs) in 12 loci (e.g., TCF7L2, IDE/KIF11/HHEX, SLC30A8, CDKAL1, PKN2, IGF2BP2, FLJ39370, and EXT2/ALX4) associated with type 2 diabetes in European-derived populations were genotyped in 993 African American type 2 diabetic and 1,054 African American control subjects. Additionally, 68 ancestry-informative markers were genotyped to account for the impact of admixture on association results.Little evidence of association was observed between SNPs, with the exception of those in TCF7L2, and type 2 diabetes in African Americans. One TCF7L2 SNP (rs7903146) showed compelling evidence of association with type 2 diabetes (admixture-adjusted additive P [P(a)] = 1.59 x 10(-6)). Only the intragenic SNP on 11p12 (rs9300039, dominant P [P(d)] = 0.029) was also associated with type 2 diabetes after admixture adjustments. Interestingly, four of the SNPs are monomorphic in the Yoruba population of the HAPMAP project, with only the risk allele from the populations of European descent present.Results suggest that these variants do not significantly contribute to interindividual susceptibility to type 2 diabetes in African Americans. Consequently, genes contributing to type 2 diabetes in African Americans may, in part, be different from those in European-derived study populations. High frequency of risk alleles in several of these genes may, however, contribute to the increased prevalence of type 2 diabetes in African Americans.
| S-EPMC2494685 | biostudies-literature
Project description:ObjectiveThis study aimed to examine single-nucleotide polymorphisms (SNPs) of seven previously reported obesity genes in East Asians and to analyse their associations and synergistic effects on obesity in the Taiwanese population.DesignCross-sectional study.SettingOne medical centre in northern Taiwan.ParticipantsA total of 323 non-obese and 264 obese participants were recruited. The threshold for obesity in this study was a body mass index of ≥27 kg/m(2), as defined by the Ministry of Health and Welfare in Taiwan. The study was performed with the approval of the institutional review board of MacKay Memorial Hospital, Taipei, Taiwan (application number 12MMHIS106).Outcome measuresWe analysed the genotype distributions of seven SNPs localising to the PPARγ2, GNB3, SDC3, ADRB2, FTO, PPARγ and ESR1 genes in obese and non-obese groups and then paired obesity-related SNPs to determine if they have synergistic effects on obesity.ResultsAnalysis of the genotype distributions in obese and non-obese groups revealed only a significant positive correlation between an SNP in rs2282440-syndecan 3 (SDC3) and obesity in the Taiwanese population (p=0.006). In addition, the T/T genotype of SDC3 was significantly associated with a larger waist and hip circumference, higher body fat percentage and lower high-density lipoprotein cholesterol. Moreover, the combination of the rs2282440-SDC3T/T genotype with the rs1801282-peroxisome proliferator-activated receptor-gamma2 gene (PPARγ2) G carrier genotype was strongly associated with obesity (OR=6.77).ConclusionsWe found that the rs2282440-SDC3T/T genotype is associated with obesity in the Taiwanese population. Furthermore, there is a synergistic effect of the high-risk alleles of the SDC3 and PPARγ2 genes on the obese phenotype in the Taiwanese population.Trial registration number12MMHIS106; Results.
| S-EPMC4986083 | biostudies-literature
Project description:INTRODUCTION: Migraine is a chronic, neurovascular polygenic disease where genetic and environmental factors are involved in its etiology. Dysfunction of neuronal ion transportation can provide a model for predisposition for common forms of migraine. Mutations in genes encoding ion channels disturb the rhythmic function of exposed tissue that may also explain the episodic nature of migraine. Our aim was to study the single nucleotide polymorphisms of CACNA1A gene in migraine patients. MATERIALS AND METHODS: The subjects were the patients of migraine, in the age range of 18-80 years, diagnosed by a Neurologist, as per the diagnostic criteria of International Headache Society (IHS) Classification 2004 after excluding other causes of headache by clinical examination and relevant investigations. The controls were the age and sex matched healthy persons from the same population excluding the relatives of patients. Only those patients and the controls, who voluntarily participated in the study, were taken and their blood samples were taken for the study. Deoxyribonucleic acid (DNA) extraction was performed according to the manufacturer's protocol for Qiagen DNA extraction kits (Qiagen, Hilden, NRW, Germany). DNA content was quantified by spectrophotometric absorption (Nanodrop Spectrophotometer, BioLab, Scoresby, VIC, Australia). Polymerase chain reaction was performed using an iCycler Thermal Cycler (Bio.Rad, Hercules, CA, USA). The polymorphic analysis of CACNA1A gene was carried out by two methods: Restriction fragment length polymorphism and sequencing. RESULTS: The study included a total of 25 patients of migraine, diagnosed on out-patient department basis as per IHS Classification 2004 and compared with age and sex matched 25 healthy controls. Most of the patients 23 (92%) were below the age of 50 years. 20 of the patients (80%) were females and 5 (20%) were males. The polymorphic analysis of CACNA1A gene revealed the presence of only the wild form of the gene for the codon E993V in both case and control groups. CONCLUSION: In our study, we could not find any polymorphism of CACNA1A gene in the selected patients. Instead the wild type of genotype was found in both patients and controls. This negative result presented here, implies that if the CACNA1A gene is involved in typical migraine (with and without aura), its contribution is very modest and therefore difficult to discern. Nevertheless, there are other genes that could be considered potential candidates for typical migraine susceptibility for which further research is needed.
| S-EPMC4065480 | biostudies-other
Project description:We studied several methods for selecting single-nucleotide polymorphisms (SNPs) in a disease association study. Two major categories for analytical strategy are the univariate and the set selection approaches. The univariate approach evaluates each SNP marker one at a time, while the set selection approach tests disease association of a set of SNP markers simultaneously. We examined various test statistics that can be utilized in testing disease association and also reviewed several multiple testing procedures that can properly control the family-wise error rates when the univariate approach is applied to multiple markers. The set association methods were then briefly reviewed. Finally, we applied these methods to the data from Collaborative Study on the Genetics of Alcoholism (COGA).
| S-EPMC1866686 | biostudies-literature