Search results for "Disposition"
showing 10 items of 832 documents
Replication of interleukin 23 receptor and autophagy-related 16-like 1 association in adult- and pediatric-onset inflammatory bowel disease in Italy.
2008
AIM: To investigate gene variants in a large Italian inflammatory bowel disease (IBD) cohort, and to analyze the correlation of sub-phenotypes (including age at diagnosis) and epistatic interaction with other IBD genes. METHODS: Total of 763 patients with Crohn's disease (CD, 189 diagnosed at age < 19 years), 843 with ulcerative colitis (UC, 179 diagnosed < 19 years), 749 healthy controls, and 546 healthy parents (273 trios) were included in the study. The rs2241880 [autophagy-related 16-like 1 (ATG16L1)], rs11209026 and rs7517847 [interleukin 23 receptor (IL23R)], rs2066844, rs2066845, rs2066847 (CARD15), rs1050152 (OCTN1), and rs2631367 (OCTN2) gene variants were genotyped. RESULTS: The f…
DLG5 variants do not influence susceptibility to inflammatory bowel disease in the Scottish population
2005
Introduction: Recent data have suggested that specific haplotypic variants of the DLG5 gene on chromosome 10q23 may be associated with susceptibility to inflammatory bowel disease (IBD) in Germany. Haplotype D, notably characterised by the presence of a G→A substitution at nucleotide 113, was associated with susceptibility to Crohn’s disease (CD) whereas an extended haplotype A conferred protection. Aims: Association of DLG5 haplotypic variants with disease susceptibility, genotype-phenotype relationships, and epistasis with CARD15 was investigated in the Scottish population. Patients and methods: A total of 374 CD, 305 ulcerative colitis (UC), and 294 healthy controls (HC) were studied. Ge…
Statistical colocalization of monocyte gene expression and genetic risk variants for type 1 diabetes
2012
One mechanism by which disease-associated DNA variation can alter disease risk is altering gene expression. However, linkage disequilibrium (LD) between variants, mostly single-nucleotide polymorphisms (SNPs), means it is not sufficient to show that a particular variant associates with both disease and expression, as there could be two distinct causal variants in LD. Here, we describe a formal statistical test of colocalization and apply it to type 1 diabetes (T1D)-associated regions identified mostly through genome-wide association studies and expression quantitative trait loci (eQTLs) discovered in a recently determined large monocyte expression data set from the Gutenberg Health Study (1…
No association of alcohol dependence with HOMER 1 and 2 genetic variants.
2010
Several lines of evidence indicate that alterations of the central cortico-accumbens glutamate pathway are involved in the development and maintenance of alcohol- and substance-use disorders. The HOMER protein family is encoded by 3 genes HOMER (1–3) which are components of the excitatory postsynaptic density complex and function to modulate synaptic activity by the regulation of glutamate signaling. HOMER 1 and 2 have been reported to contribute to chronic alcohol-induced long-term neurochemical changes in the endogenous reward system. Data from animal models suggest a potential role of the Homer protein family in the development of alcohol and substance use. The aim of this study is to as…
Genome-wide association data provide further support for an association between 5-HTTLPR and major depressive disorder.
2013
Abstract Background Dysfunctions of serotonergic neurotransmission are supposed to be involved in the pathogenesis of psychiatric disorders such as major depressive disorder (MDD). The concentration of serotonin (5-hydroxytryptamine, 5-HT) in the synaptic cleft is essentially regulated by the 5-HT transporter (5-HTT). A length polymorphism repeat in the 5-HTT promoter region, termed 5-HTTLPR, has been commonly investigated for an association with psychiatric disorders. Methods Genotyping of the 5-HTTLPR is time-consuming and technically challenging. Recently, a two-SNP haplotype was identified that tags the 5-HTTLPR at r 2 =0.775. This allows extraction of 5-HTTLPR genotype information from…
Association of Common Variants in NPPA and NPPB with Circulating Natriuretic Peptides and Blood Pressure
2009
We examined the association of common variants at the NPPA-NPPB locus with circulating concentrations of the natriuretic peptides, which have blood pressure-lowering properties. We genotyped SNPs at the NPPA-NPPB locus in 14,743 individuals of European ancestry, and identified associations of plasma atrial natriuretic peptide with rs5068 (P = 8 x 10(-70)), rs198358 (P = 8 x 10(-30)) and rs632793 (P = 2 x 10(-10)), and of plasma B-type natriuretic peptide with rs5068 (P = 3 x 10(-12)), rs198358 (P = 1 x 10(-25)) and rs632793 (P = 2 x 10(-68)). In 29,717 individuals, the alleles of rs5068 and rs198358 that showed association with increased circulating natriuretic peptide concentrations were a…
Replication of previous genome-wide association studies of psychiatric diseases in a large schizophrenia case-control sample from Spain.
2014
Genome wide association studies (GWAS) has allowed the discovery of some interesting risk variants for schizophrenia (SCZ). However, this high-throughput approach presents some limitations, being the most important the necessity of highly restrictive statistical corrections as well as the loss of statistical power inherent to the use of a Single Nucleotide Polymorphism (SNP) analysis approach. These problems can be partially solved through the use of a polygenic approach. We performed a genotyping study in SCZ using 86 previously associated SNPs identified by GWAS of SCZ, bipolar disorder (BPD) and autistic spectrum disorder (ASD) patients. The sample consisted of 3063 independent cases wit…
IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes
2018
GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 ca…
Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease
2011
1. The CARDIoGRAM Consortium. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nature Genetics. 2011;43:333–338. ### Study Hypothesis Recently, genome-wide association studies (GWAS) have identified several common variants that are associated with risk of coronary artery disease (CAD) and myocardial infarction (MI). The authors state that the current loci discovered in CAD and MI GWAS explain only a small fraction of the heritability of this complex disease. The authors hypothesized that a larger study would provide more power to discover common variants with modest effect sizes. Therefore, they formed the Coronary ARtery DIsease Genome-wid…
Lack of association between estrogen receptor 1 gene polymorphisms and multiple sclerosis in southern Italy in humans
2002
Estrogen receptor 1 gene polymorphisms (ESR1) have been found to be associated with multiple sclerosis (MS) in both Japanese and Finnish populations. We investigated the association between ESR1 polymorphisms (PvuII and XbaI) and MS in a study of 132 MS patients and 129 controls from the same geographic background (southern Italy). Allelic and genotypic frequencies were not different between MS patients and population controls for either the PvuII or XbaI polymorphism. This result suggests that the association between a given disease and a genomic characteristic must be confirmed by separate investigations in different populations. © 2002 Elsevier Science Ireland Ltd. All rights reserved.