Search results for "association study"
showing 10 items of 374 documents
A two-stage genome-wide association study of sporadic amyotrophic lateral sclerosis
2009
The cause of sporadic amyotrophic lateral sclerosis (ALS) is largely unknown, but genetic factors are thought to play a significant role in determining susceptibility to motor neuron degeneration. To identify genetic variants altering risk of ALS, we undertook a two-stage genome-wide association study (GWAS): we followed our initial GWAS of 545 066 SNPs in 553 individuals with ALS and 2338 controls by testing the 7600 most associated SNPs from the first stage in three independent cohorts consisting of 2160 cases and 3008 controls. None of the SNPs selected for replication exceeded the Bonferroni threshold for significance. The two most significantly associated SNPs, rs2708909 and rs2708851 …
Type 1 Diabetes and Autoimmune Thyroid Disease—The Genetic Link
2021
Type 1 diabetes (T1D) and autoimmune thyroid disease (AITD) are the most frequent chronic autoimmune diseases worldwide. Several autoimmune endocrine and non-endocrine disorders tend to occur together. T1D and AITD often cluster in individuals and families, seen in the formation of autoimmune polyendocrinopathy (AP). The close relationship between these two diseases is largely explained by sharing a common genetic background. The HLA antigens DQ2 (DQA1*0501-DQB1*0201) and DQ8 (DQA1*0301-DQB1*0302), tightly linked with DR3 and DR4, are the major common genetic predisposition. Moreover, functional single nucleotide polymorphisms (or rare variants) of various genes, such as the cytotoxic T-lym…
Polygenic association between attention-deficit/hyperactivity disorder liability and cognitive impairments.
2022
AbstractBackgroundA recent genome-wide association study (GWAS) identified 12 independent loci significantly associated with attention-deficit/hyperactivity disorder (ADHD). Polygenic risk scores (PRS), derived from the GWAS, can be used to assess genetic overlap between ADHD and other traits. Using ADHD samples from several international sites, we derived PRS for ADHD from the recent GWAS to test whether genetic variants that contribute to ADHD also influence two cognitive functions that show strong association with ADHD: attention regulation and response inhibition, captured by reaction time variability (RTV) and commission errors (CE).MethodsThe discovery GWAS included 19 099 ADHD cases …
Association Study of Genetic Variants in the 14q11 - 14q13 Proteasomal Genes Cluster with Juvenile Idiopathic Arthritis (JIA) in Latvian Population
2009
Association Study of Genetic Variants in the 14q11 - 14q13 Proteasomal Genes Cluster with Juvenile Idiopathic Arthritis (JIA) in Latvian Population The possible role of proteasomes in the development of autoimmune diseases was hypothesised after discovery of the involvement of proteasomal LMP2 and LMP7 subunits in antigene processing. The objective of this study was to determine the association between allelic variants of the genes encoding proteasomal proteins PSME1, PSME2 and PSMA6 and juvenile idiopathic arthritis (JIA) in the Latvian population. One Indel G-4543 CA-4544 →GA and four SNPs related to the PSMA6 gene (A-2486 →G and C-1910 →T, upstream promoter, C-110 →A of promoter, and C-8…
FPGA-based Acceleration of Detecting Statistical Epistasis in GWAS
2014
Abstract Genotype-by-genotype interactions (epistasis) are believed to be a significant source of unexplained genetic variation causing complex chronic diseases but have been ignored in genome-wide association studies (GWAS) due to the computational burden of analysis. In this work we show how to benefit from FPGA technology for highly parallel creation of contingency tables in a systolic chain with a subsequent statistical test. We present the implementation for the FPGA-based hardware platform RIVYERA S6-LX150 containing 128 Xilinx Spartan6-LX150 FPGAs. For performance evaluation we compare against the method iLOCi[9]. iLOCi claims to outperform other available tools in terms of accuracy.…
Genome-wide association study and mouse expression data identify a highly conserved 32 kb intergenic region between WNT3 and WNT9b as possible suscep…
2014
Item does not contain fulltext Bladder exstrophy-epispadias complex (BEEC), the severe end of the urorectal malformation spectrum, has a profound impact on continence as well as sexual and renal functions. It is widely accepted that for the majority of cases the genetic basis appears to be multifactorial. Here, we report the first study which utilizes genome-wide association methods to analyze a cohort comprising patients presenting the most common BEEC form, classic bladder exstrophy (CBE), to identify common variation associated with risk for isolated CBE. We employed discovery and follow-up samples comprising 218 cases/865 controls and 78 trios in total, all of European descent. Our disc…
Macrophage scavenger receptor 1 mediates lipid-induced inflammation in non-alcoholic fatty liver disease.
2022
Background & Aims: Obesity-associated inflammation is a key player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the role of macrophage scavenger receptor 1 (MSR1, CD204) remains incompletely understood. Methods: A total of 170 NAFLD liver biopsies were processed for transcriptomic analysis and correlated with clinicopathological features. Msr1(-/-) and wild-type mice were subjected to a 16-week high-fat and high-cholesterol diet. Mice and ex vivo human liver slices were treated with a monoclonal antibody against MSR1. Genetic susceptibility was assessed using genome-wide association study data from 1,483 patients with NAFLD and 430,101 participants of the U…
Genome-Wide Inhibition of Pro-atherogenic Gene Expression by Multi-STAT Targeting Compounds as a Novel Treatment Strategy of CVDs.
2018
Cardiovascular diseases (CVDs), including atherosclerosis, are globally the leading cause of death. Key factors contributing to onset and progression of atherosclerosis include the pro-inflammatory cytokines Interferon (IFN)a and IFN? and the Pattern Recognition Receptor (PRR) Toll-like receptor 4 (TLR4). Together, they trigger activation of Signal Transducer and Activator of Transcription (STAT)s. Searches for compounds targeting the pTyr-SH2 interaction area of STAT3, yielded many small molecules, including STATTIC and STX-0119. However, many of these inhibitors do not seem STAT3-specific. We hypothesized that multi-STAT-inhibitors that simultaneously block STAT1, STAT2, and STAT3 activit…
Association of a single nucleotide polymorphism of RANK gene with blood pressure in Spanish women
2020
Abstract In addition to governing key functions in bone metabolism and the immune system, the RANK/RANKL/OPG system plays a role in the vascular system, particularly in vascular calcification and atherosclerosis. Given that these 2 phenotypes are considered a major cause of high blood pressure (BP), in this study we analyzed the association of SNPs in RANK and OPG genes with blood pressure. An observational study was conducted of 2 SNPs in the RANK gene (rs884205 and rs78326403) and 1 in the OPG gene (rs4876869) with systolic (SBP) and diastolic blood pressure (DBP) in a cohort of 695 women. Data analysis revealed a statistically significant association between the SNP rs884205 and BP press…
KCND3 is a novel susceptibility locus for early repolarization
2019
AbstractThe presence of an early repolarization pattern (ERP) on the surface electrocardiogram (ECG) is associated with risk of ventricular fibrillation and sudden cardiac death. Family studies have shown that ERP is a highly heritable trait but molecular genetic determinants are unknown. We assessed the ERP in 12-lead ECGs of 39,456 individuals and conducted a two-stage meta-analysis of genome-wide association studies (GWAS). In the discovery phase, we included 2,181 cases and 23,641 controls from eight European ancestry studies and identified 19 genome-wide significant (p<5E-8) variants in the KCND3 (potassium voltage gated channel subfamily D member 3) gene with a p-value of 4.6E-10. …