Search results for "Genome-Wide Association Study"

2021

The cell—cell signaling gene CDH13 is associated with a wide spectrum of neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), autism, and major depression. CDH13 regulates axonal outgrowth and synapse formation, substantiating its relevance for neurodevelopmental processes. Several studies support the influence of CDH13 on personality traits, behavior, and executive functions. However, evidence for functional effects of common gene variation in the CDH13 gene in humans is sparse. Therefore, we tested for association of a functional intronic CDH13 SNP rs2199430 with ADHD in a sample of 998 adult patients and 884 healthy controls. The Big Five personality tra…

An APOE haplotype associated with decreased ε4 expression increases the risk of late onset Alzheimer's disease.

2011

This paper addresses a tenet of the literature on APOE, i.e., the relationship between the effects of the e4, one of the established genetic risk factor for Alzheimer's disease (AD), and its expression levels as determined by APOE promoter polymorphisms. Five polymorphisms (-491 rs449647, -427 rs769446, -219 rs405509, and e rs429358-rs7412) were studied in 1308 AD patients and 1082 control individuals from the Central-Northern Italy. Major findings of the present study are the following: 1) the variants -219T and e4 increase the risk for late onset AD (LOAD) when they are both present in cis on the same chromosome (in phase); 2) the correlation between the haplotype (-219T/e4) and AD risk p…

On the origin of mongrels: evolutionary history of free-breeding dogs in Eurasia

2015

Although a large part of the global domestic dog population is free-ranging and free-breeding, knowledge of genetic diversity in these free-breeding dogs (FBDs) and their ancestry relations to pure-breed dogs is limited, and the indigenous status of FBDs in Asia is still uncertain. We analyse genome-wide SNP variability of FBDs across Eurasia, and show that they display weak genetic structure and are genetically distinct from pure-breed dogs rather than constituting an admixture of breeds. Our results suggest that modern European breeds originated locally from European FBDs. East Asian and Arctic breeds show closest affinity to East Asian FBDs, and they both represent the earliest branching…

Genetics and novel aspects of therapies in systemic lupus erythematosus.

2015

Autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, autoimmune hepatitis and inflammatory bowel disease, have complex pathogeneses and the factors which cause these disorders are not well understood. But all have in common that they arise from a dysfunction of the immune system, interpreting self components as foreign antigens. Systemic lupus erythematosus (SLE) is one of these complex inflammatory disorders that mainly affects women and can lead to inflammation and severe damage of virtually any tissue and organ. Recently, the application of advanced techniques of genome-wide scanning revealed more genetic information about SLE than previously possible. These case-contro…

A motif-independent metric for DNA sequence specificity

2011

Abstract Background Genome-wide mapping of protein-DNA interactions has been widely used to investigate biological functions of the genome. An important question is to what extent such interactions are regulated at the DNA sequence level. However, current investigation is hampered by the lack of computational methods for systematic evaluating sequence specificity. Results We present a simple, unbiased quantitative measure for DNA sequence specificity called the Motif Independent Measure (MIM). By analyzing both simulated and real experimental data, we found that the MIM measure can be used to detect sequence specificity independent of presence of transcription factor (TF) binding motifs. We…

Duration of untreated psychosis in first-episode psychosis is not associated with common genetic variants for major psychiatric conditions: results f…

2021

The EU-GEI Project is funded by the European Community’s Seventh Framework Programme under grant agreement No. HEALTH-F2-2010–241909 (Project EU-GEI).

Variation in the glucose transporter gene SLC2A2 is associated with glycemic response to metformin

2016

Metformin is the first-line antidiabetic drug with over 100 million users worldwide, yet its mechanism of action remains unclear(1). Here the Metformin Genetics (MetGen) Consortium reports a three-stage genome-wide association study (GWAS), consisting of 13,123 participants of different ancestries. The C allele of rs8192675 in the intron of SLC2A2, which encodes the facilitated glucose transporter GLUT2, was associated with a 0.17% (P = 6.6 x 10(-14)) greater metformin-induced reduction in hemoglobin A1c (HbA1c) in 10,577 participants of European ancestry. rs8192675 was the top cis expression quantitative trait locus (cis-eQTL) for SLC2A2 in 1,226 human liver samples, suggesting a key role …

Novel genetic variant in FTO influences insulin levels and insulin resistance in severely obese children and adolescents.

2008

Background: The global prevalence of obesity and overweight is increasing rapidly among adults as well as among children and adolescents. Recent genome-wide association studies have provided strong support for association between variants in the FTO gene and obesity. We sequenced regions of the FTO gene to identify novel variants that are associated with obesity and related metabolic traits. Results: We screened exons 3 and 4 including exon-intron boundaries in FTO in 48 obese children and adolescents and identified three novel single nucleotide polymorphism in the fourth intronic region, (c.896 + 37A > G, c.896 + 117C > G and c.896 + 223A > G). We further genotyped c.896 + 223A > G in 962 …

New candidates for CD4 T cell pathogenicity in experimental neuroinflammation and multiple sclerosis

2015

Multiple sclerosis is a chronic autoimmune demyelinating disease of the central nervous system, which is thought to be triggered by environmental factors in genetically susceptible individuals leading to activation of autoreactive T lymphocytes. Large multi-centre genome-wide association studies have identified multiple genetic risk loci in multiple sclerosis. In this study, we investigated T cell transcriptomic changes in experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis. We correlated these findings with the multiple sclerosis risk genes postulated by the most recent Immunochip analysis and found that multiple sclerosis susceptibility genes were significant…

X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis

2021

Background & aims: Genome-wide association studies in primary biliary cholangitis (PBC) have failed to find X chromosome (chrX) variants associated with the disease. Here, we specifically explore the chrX contribution to PBC, a sexually dimorphic complex autoimmune disease. Methods: We performed a chrX-wide association study, including genotype data from 5 genome-wide association studies (from Italy, United Kingdom, Canada, China, and Japan; 5244 case patients and 11,875 control individuals). Results: Single-marker association analyses found approximately 100 loci displaying P < 5 × 10-4, with the most significant being a signal within the OTUD5 gene (rs3027490; P = 4.80 × 10-6; odds…