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Genome-wide association studies highlight novel risk loci for septal defects and left-sided congenital heart defects.

BACKGROUND: Congenital heart defects (CHD) are structural defects of the heart affecting approximately 1% of newborns. They exhibit low penetrance and non-Mendelian patterns of inheritance as varied and complex traits. While genetic factors are known to play an important role in the development of CHD, the specific genetics remain unknown for the majority of patients. To elucidate the underlying genetic risk, we performed a genome wide association study (GWAS) of CHDs in general and specific CHD subgroups using the FinnGen Release 10 (R10) (N > 393,000), followed by functional fine-mapping thr

Large-scale genome-wide association studies reveal the genetic causal etiology between air pollutants and autoimmune diseases.

BACKGROUND: Epidemiological evidence links a close correlation between long-term exposure to air pollutants and autoimmune diseases, while the causality remained unknown. METHODS: Two-sample Mendelian randomization (TSMR) was used to investigate the role of PM10, PM2.5, NO2, and NOX (N = 423,796-456,380) in 15 autoimmune diseases (N = 14,890-314,995) using data from large European GWASs including UKB, FINNGEN, IMSGC, and IPSCSG. Multivariable Mendelian randomization (MVMR) was conducted to investigate the direct effect of each air pollutant and the mediating role of common factors, including

Integration of genome-wide association studies (GWAS) and microbiome data highlights the impact of sulfate-reducing bacteria on Alzheimer's disease.

BACKGROUND: observational studies have indicated that gut microbiome dysbiosis was associated with Alzheimer's disease (ad). However, the results are largely inconsistent and it remains unknown whether the association is causal in nature. METHODS: leveraging observational studies and genome-wide association studies (GWAS) on the gut microbiome in ad patients, we pooled the microbiome data (N = 1,109) to screen the microbiota significantly altered in ad patients and then conducted Mendelian randomisation (MR) study to determine the causal associations between altered microbiota (N = 18,340) an

PhenoExplorer: An Interactive Web-based Platform for Exploring (Epi)Genome-Wide Associations Using a Swiss Population-based Study.

The recent advent of high-throughput sequencing technologies has allowed exploring the contribution of thousands of genomic, epigenomic, transcriptomic, or proteomic variants to complex phenotypic traits. Here, we sought to conduct large-scale (Epi)Genome-Wide Association Studies (GWAS/EWAS) to investigate the associations between genomic (Single Nucleotide Polymorphism; SNP) and epigenomic (Cytosine-Phospho-Guanine; CpG) markers, with multiple phenotypic traits in a population-based context. We used data from SKIPOGH, a family- and population-based cohort conducted in the cities of Lausanne,

Genome-Wide Association Studies Based on Equine Joint Angle Measurements Reveal New QTL Affecting the Conformation of Horses.

The evaluation of conformation traits is an important part of selection for breeding stallions and mares. Some of these judged conformation traits involve joint angles that are associated with performance, health, and longevity. To improve our understanding of the genetic background of joint angles in horses, we have objectively measured the angles of the poll, elbow, carpal, fetlock (front and hind), hip, stifle, and hock joints based on one photograph of each of the 300 Franches-Montagnes (FM) and 224 Lipizzan (LIP) horses. After quality control, genome-wide association studies (GWASs) for t

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine…

Genome-wide study to detect single nucleotide polymorphisms associated with visceral and subcutaneous fat deposition in Holstein dairy cows.

Excessive abdominal fat might be associated with more severe metabolic disorders in Holstein cows. Our hypothesis was that there are genetic differences between cows with low and high abdominal fat deposition and a normal cover of subcutaneous adipose tissue. The objective of this study was to assess the genetic basis for variation in visceral adiposity in US Holstein cows. The study included adult Holstein cows sampled from a slaughterhouse (Green Bay, WI, USA) during September 2016. Only animals with a body condition score between 2.75 and 3.25 were considered. The extent of omental fat at t

Chemotherapy-induced peripheral neuropathy: evidence from genome-wide association studies and replication within multiple myeloma patients.

BackgroundBased on the possible shared mechanisms of chemotherapy-induced peripheral neuropathy (CIPN) for different drugs, we aimed to aggregate results of all previously published genome-wide association studies (GWAS) on CIPN, and to replicate them within a cohort of multiple myeloma (MM) patients.MethodsFollowing a systematic literature search, data for CIPN associated single nucleotide polymorphisms (SNPs) with P-values- 5 were extracted; these associations were investigated within a cohort of 983 German MM patients treated with bortezomib, thalidomide or vincristine. Cases were subjects

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… On the other hand, recent robust genome-wide association studies (GWASs), mainly focussing on individual chemotherapeutic agents, have introduced several genetic markers to predict the risk of CIPN. … To maximize the search coverage, medical subject heading (MeSH) terms for the “genome-wide association study” and “chemotherapy” and “neuropathy” were included. …

Pooled analysis of genome-wide association studies of cervical intraepithelial neoplasia 3 (CIN3) identifies a new susceptibility locus.

Recent genome-wide association studies (GWASs) in subjects of European descent have identified associations between cervical cancer risk and three independent loci as well as multiple classical human leukocyte antigen (HLA) alleles at 6p21.3. To search for novel loci associated with development of cervical cancer, we performed a pooled analysis of data from two GWASs by imputing over 10 million genetic variants and 424 classical HLA alleles, for 1,553 intraepithelial neoplasia 3 (CIN3), 81 cervical cancer and 4,442 controls from the Swedish population. Notable findings were validated in an ind

Further investigation in europeans of susceptibility variants for polycystic ovary syndrome discovered in genome-wide association studies of Chinese individuals.

CONTEXT: Two genome-wide association studies (GWAS) of polycystic ovary syndrome (PCOS) have identified 11 susceptibility loci in Chinese individuals. Some of the risk loci identified in Chinese cohorts, mostly from the first GWAS, have been replicated in Europeans. Replication of the loci from the second GWAS in European cohorts is necessary to determine whether the same variants confer risk for PCOS in multiple ethnicities. OBJECTIVE: The objective of the study was to determine the effects of the Chinese GWAS loci in European-origin individuals. DESIGN: This was a genetic association study

Down the line from genome-wide association studies in inflammatory bowel disease: the resulting clinical benefits and the outlook for the future.

Inflammatory bowel disease (IBD), consisting of Crohn's disease and ulcerative colitis, is a chronic inflammatory disease of the gut. The etiology of IBD is complex, involving genetic as well as environmental factors. Genetic studies have identified 163 genetic risk loci for IBD, which have led to new insights into the biological mechanisms of the disease. The currently known IBD risk loci show an almost 75% overlap with genetic risk loci for other immune mediated diseases. Current studies are focused on the translation of the identified risk loci to clinical practice. The first steps towards

A Genome-Wide Association Study Identifies Candidate SNPs and Genes Associated with Body Weight in the Northern Snakehead (Channa argus) Using a 50K SNP Array.

Body weight is the principal economic trait in snakehead aquaculture, yet the genetic architecture of growth in the northern snakehead (Channa argus) remains largely unexplored. We performed a genome-wide association study (GWAS) for body weight in 205 cultured C. argus genotyped with a 50K SNP array. After quality control, 47,123 autosomal SNPs were tested under a univariate linear mixed model in GEMMA that accounted for genomic relatedness. One SNP on chromosome 7 (Chr07:1,329,732) exceeded the Bonferroni genome-wide threshold, and 14 SNPs reached a suggestive threshold, forming two candidat…

A genome-wide association study identifies new loci associated with response to SARS-CoV-2 mRNA-1273 vaccine in a cohort of healthy healthcare workers.

INTRODUCTION: The COVID-19 pandemic had significant global public health consequences, affecting over 200 countries and regions by 2020. The development and efficacy of specific vaccines, such as the mRNA-1273 (Spikevax®) vaccine developed by Moderna Inc., have substantially reduced the impact of the pandemic and mitigated its consequences. This study aims to identify novel genetic loci associated with the effectiveness of the mRNA-1273 vaccine, as measured by elevated anti-Spike (anti-S) IgG levels at multiple time points post-vaccination. MATERIALS AND METHODS: We conducted three genome-wid

Genome-Wide Association Study Reveals Quantitative Trait Loci and Candidate Genes Associated with High Interferon-gamma Production in Holstein Cattle Naturally Infected with Mycobacterium Bovis.

Mycobacterium bovis (Mb) is the causative agent of bovine tuberculosis (bTb). Genetic selection aiming to identify less susceptible animals has been proposed as a complementary measure in ongoing programs toward controlling Mb infection. However, individual animal phenotypes for bTb based on interferon-gamma (IFNɣ) and its use in bovine selective breeding programs have not been explored. In the current study, IFNɣ production was measured using a specific IFNɣ ELISA kit in bovine purified protein derivative (bPPD)-stimulated blood samples collected from Holstein cattle. DNA isolated from the pe

Statistical Learning of Large-Scale Genetic Data: How to Run a Genome-Wide Association Study of Gene-Expression Data Using the 1000 Genomes Project Data.

OBJECTIVE: To assess clinical characteristics, management strategies and in-hospital outcome among high-risk patients of non-ST elevation myocardial infarction. METHODS: The retrospective cross-sectional study was conducted at Tabba Heart Institute, Karachi, and comprised data from July 2013 to December 2016 of adult non-ST elevation myocardial infarction patients who had first cardiac event having Global Registry of Acute Coronary Eventsrisk score>140. Subcategories were formed on the basis of score range 140-159, 160-189 and ?190.Stata 12.1 was used for data analysis. RESULTS: Of the 817 p

Copy number variant-based genome wide association study reveals immune-related genes associated with parasite resistance in a heritage sheep breed from the United States.

Florida Native is a heritage sheep breed in the United States and expresses superior ability to regulate gastrointestinal nematodes. The objective of the present study was to investigate the importance of copy number variants (CNVs) on resistance to natural Haemonchus contortus infections. A total of 300 Florida Native sheep were evaluated. Phenotypic records included fecal egg count (FEC, eggs/gram), FAMACHA© score, percentage cell volume (PCV, %), body condition score (BCS) and average daily gain (ADG, kg). Sheep were genotyped using the GGP Ovine 50K single nucleotide polymorphism (SNP) chi

Genome-Wide Association Study (GWAS) on Bilirubin Concentrations in Subjects with Metabolic Syndrome: Sex-Specific GWAS Analysis and Gene-Diet Interactions in a Mediterranean Population.

Although, for decades, increased serum bilirubin concentrations were considered a threatening sign of underlying liver disease and had been associated with neonatal jaundice, data from recent years show that bilirubin is a powerful antioxidant and suggest that slightly increased serum bilirubin concentrations are protective against oxidative stress-related diseases, such as cardiovascular diseases. Therefore, a better understanding of the gene-diet interactions in determining serum bilirubin concentrations is needed. None of the previous genome-wide association studies (GWAS) on bilirubin conc

A multi-ethnic genome-wide association study identifies novel loci for non-syndromic cleft lip with or without cleft palate on 2p24.2, 17q23 and 19q13.

Orofacial clefts (OFCs), which include non-syndromic cleft lip with or without cleft palate (CL/P), are among the most common birth defects in humans, affecting approximately 1 in 700 newborns. CL/P is phenotypically heterogeneous and has a complex etiology caused by genetic and environmental factors. Previous genome-wide association studies (GWASs) have identified at least 15 risk loci for CL/P. As these loci do not account for all of the genetic variance of CL/P, we hypothesized the existence of additional risk loci. We conducted a multiethnic GWAS in 6480 participants (823 unrelated cases,

Use of expression data and the CGEMS genome-wide breast cancer association study to identify genes that may modify risk in BRCA1/2 mutation carriers.

Germline mutations in BRCA1 or BRCA2 confer an increased lifetime risk of developing breast or ovarian cancer, but variable penetrance suggests that cancer susceptibility is influenced in part by modifier genes. Microarray expression profiling was conducted for 69 irradiated lymphoblastoid cell lines derived from healthy controls, or from cancer-affected women with a strong family history of breast and ovarian cancer carrying pathogenic mutations in BRCA1 or BRCA2, or with no BRCA1/2 mutations (BRCAX). Genes discriminating between BRCA1, BRCA2 or BRCAX and controls were stratified based on irr