Search results for "Genome-wide"
showing 10 items of 410 documents
Rare variant analyses across multiethnic cohorts identify novel genes for refractive error
2023
Refractive error, measured here as mean spherical equivalent (SER), is a complex eye condition caused by both genetic and environmental factors. Individuals with strong positive or negative values of SER require spectacles or other approaches for vision correction. Common genetic risk factors have been identified by genome-wide association studies (GWAS), but a great part of the refractive error heritability is still missing. Some of this heritability may be explained by rare variants (minor allele frequency [MAF] ≤ 0.01.). We performed multiple gene-based association tests of mean Spherical Equivalent with rare variants in exome array data from the Consortium for Refractive Error and Myopi…
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…
Variants associated with HHIP expression have sex-differential effects on lung function [version 1; peer review: 2 approved]
2020
Background: Lung function is highly heritable and differs between the sexes throughout life. However, little is known about sex-differential genetic effects on lung function. We aimed to conduct the first genome-wide genotype-by-sex interaction study on lung function to identify genetic effects that differ between males and females. Methods: We tested for interactions between 7,745,864 variants and sex on spirometry-based measures of lung function in UK Biobank (N=303,612), and sought replication in 75,696 independent individuals from the SpiroMeta consortium. Results: Five independent single-nucleotide polymorphisms (SNPs) showed genome-wide significant (P<5x10-8) interactions with sex on …
Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
2023
Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on t…
Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary …
2023
Funder: British Lung Foundation (BLF); doi: https://doi.org/10.13039/501100000351
Separating the Mechanism-Based and Off-Target Actions of Cholesteryl Ester Transfer Protein Inhibitors With CETP Gene Polymorphisms
2010
Background— Cholesteryl ester transfer protein (CETP) inhibitors raise high-density lipoprotein (HDL) cholesterol, but torcetrapib, the first-in-class inhibitor tested in a large outcome trial, caused an unexpected blood pressure elevation and increased cardiovascular events. Whether the hypertensive effect resulted from CETP inhibition or an off-target action of torcetrapib has been debated. We hypothesized that common single-nucleotide polymorphisms in the CETP gene could help distinguish mechanism-based from off-target actions of CETP inhibitors to inform on the validity of CETP as a therapeutic target. Methods and Results— We compared the effect of CETP single-nucleotide polymorphisms …
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…
A Combined Multi-Cohort Approach Reveals Novel and Known Genome-Wide Selection Signatures for Wool Traits in Merino and Merino-Derived Sheep Breeds.
2019
Merino sheep represents a valuable genetic resource worldwide. In this study, we investigated selection signatures in Merino (and Merino-derived) sheep breeds using genome-wide SNP data and two different approaches: a classical F-ST-outlier method and an approach based on the analysis of local ancestry in admixed populations. In order to capture the most reliable signals, we adopted a combined, multi-cohort approach. In particular, scenarios involving four Merino breeds (Spanish Merino, Australian Merino, Chinese Merino, and Sopravissana) were tested via the local ancestry approach, while nine pair-wise breed comparisons contrasting the above breeds, as well as the Gentile di Puglia breed, …
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…