50,902 results match your criteria genome-wide association


Phylogenetic Methods for Genome-Wide Association Studies in Bacteria.

Authors:
Xavier Didelot

Methods Mol Biol 2021 ;2242:205-220

School of Life Sciences and Department of Statistics, University of Warwick, Coventry, UK.

Genome-wide association studies in bacteria have great potential to deliver a better understanding of the genetic basis of many biologically important phenotypes, including antibiotic resistance, pathogenicity, and host adaptation. Such studies need however to account for the specificities of bacterial genomics, especially in terms of population structure, homologous recombination, and genomic plasticity. A powerful way to tackle this challenge is to use a phylogenetic approach, which is based on long-standing methodology for the evolutionary analysis of bacterial genomic data. Read More

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January 2021

Genome-wide association study of cardiac troponin I in the general population.

Hum Mol Genet 2021 May 7. Epub 2021 May 7.

Division of Research and Innovation, Akershus University Hospital, 1478 Lørenskog, Norway.

Circulating cardiac troponin proteins are associated with structural heart disease and predict incident cardiovascular disease in the general population. However, the genetic contribution to cardiac troponin I (cTnI) concentrations and its causal effect on cardiovascular phenotypes is unclear. We combine data from two large population-based studies, the Trøndelag Health Study and the Generation Scotland Scottish Family Health Study and perform a genome-wide association study of high-sensitivity cTnI concentrations with 48 115 individuals. Read More

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Pediatric psoriasis induced by HLA-B46-Cw1 haplotype: A retrospective study of psoriasis onset after hematopoietic stem cell transplantation.

J Dermatol 2021 May 7. Epub 2021 May 7.

Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.

Genome-wide association studies have identified more than 60 susceptibility loci for psoriasis, highlighting the role of genetics in psoriasis development. Although the HLA region is suggested as the most prominent susceptibility locus, the role of the HLA haplotype in the development of psoriasis is unclear. The aim of this study is to investigate how HLA haplotype changes affect the onset of psoriasis and which HLA haplotypes are associated with the development of psoriasis. Read More

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Confirmation of Xp22.11 Duplication as a Germline Susceptibility Alteration in a Wilms Tumor Arising in Horseshoe Kidney.

Fetal Pediatr Pathol 2021 May 7:1-6. Epub 2021 May 7.

The Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.

Background: There is strong evidence of a genetic contribution to Wilms tumor, such as gene variation or epigenetic changes at chromosome locus 11p15. A previous genome wide association study (GWAS) of Wilms tumor identified other significant association loci including Xp22. A 4-year-old girl developed a Wilms tumor of the left isthmus of a horseshoe kidney. Read More

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A GWAS identifies novel gene associations with facial skin wrinkling and mole count in Latin-Americans.

Br J Dermatol 2021 May 6. Epub 2021 May 6.

Instituto de Alta Investigación, Universidad de Tarapacá, Arica, Arica, 1000000, Chile.

Background: Genome-wide association studies (GWAS) have identified genes influencing skin ageing and mole count in Europeans but little is known about the relevance of these (or other genes) in non-Europeans.

Objective: To conduct a GWAS for facial skin ageing and mole count in adults < 40 years old, of mixed European, Native American and African ancestry, recruited in Latin America.

Methods: Skin ageing and mole count scores were obtained from facial photographs of >6,000 individuals. Read More

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Defining functional variants associated with Alzheimer's disease in the induced immune response.

Brain Commun 2021 19;3(2):fcab083. Epub 2021 Apr 19.

Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff CF24 4HQ, UK.

Defining the mechanisms involved in the aetiology of Alzheimer's disease from genome-wide association studies alone is challenging since Alzheimer's disease is polygenic and most genetic variants are non-coding. Non-coding Alzheimer's disease risk variants can influence gene expression by affecting miRNA binding and those located within enhancers and within CTCF sites may influence gene expression through alterations in chromatin states. In addition, their function can be cell-type specific. Read More

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Cell-Type-Specific Gene Modules Related to the Regional Homogeneity of Spontaneous Brain Activity and Their Associations With Common Brain Disorders.

Front Neurosci 2021 20;15:639527. Epub 2021 Apr 20.

Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, China.

Mapping gene expression profiles to neuroimaging phenotypes in the same anatomical space provides opportunities to discover molecular substrates for human brain functional properties. Here, we aimed to identify cell-type-specific gene modules associated with the regional homogeneity (ReHo) of spontaneous brain activity and their associations with brain disorders. Fourteen gene modules were consistently associated with ReHo in the three datasets, five of which showed cell-type-specific expression (one neuron-endothelial module, one neuron module, one astrocyte module and two microglial modules) in two independent cell series of the human cerebral cortex. Read More

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Genome-wide survival study identifies a novel synaptic locus and polygenic score for cognitive progression in Parkinson's disease.

Nat Genet 2021 May 6. Epub 2021 May 6.

Translational Genomics Core of Partners HealthCare Personalized Medicine, Cambridge, MA, USA.

A key driver of patients' well-being and clinical trials for Parkinson's disease (PD) is the course that the disease takes over time (progression and prognosis). To assess how genetic variation influences the progression of PD over time to dementia, a major determinant for quality of life, we performed a longitudinal genome-wide survival study of 11.2 million variants in 3,821 patients with PD over 31,053 visits. Read More

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Uncovering genetic mechanisms of hypertension through multi-omic analysis of the kidney.

Nat Genet 2021 May 6. Epub 2021 May 6.

Centre for Biostatistics, School of Health Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.

The kidney is an organ of key relevance to blood pressure (BP) regulation, hypertension and antihypertensive treatment. However, genetically mediated renal mechanisms underlying susceptibility to hypertension remain poorly understood. We integrated genotype, gene expression, alternative splicing and DNA methylation profiles of up to 430 human kidneys to characterize the effects of BP index variants from genome-wide association studies (GWASs) on renal transcriptome and epigenome. Read More

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Kidney function and obstructive lung disease: a bidirectional Mendelian randomisation study.

Eur Respir J 2021 May 6. Epub 2021 May 6.

Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea

Background: Additional study is warranted to investigate the causal effects between kidney function and obstructive lung disease.

Methods: This study was a bidirectional two-sample Mendelian randomisation (MR) analysis. The CKDGen genome-wide association study (GWAS) meta-analysis for estimated glomerular filtration rate (eGFR) including individuals of European ancestry (N=567 460) provided the genetic instrument for kidney function and outcome summary statistics. Read More

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Lrp5 mutant and crispant zebrafish faithfully model human osteoporosis, establishing the zebrafish as a platform for CRISPR-based functional screening of osteoporosis candidate genes.

J Bone Miner Res 2021 May 6. Epub 2021 May 6.

Center for Medical Genetics Ghent, Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.

Genome-wide association studies (GWAS) have improved our understanding of the genetic architecture of common, complex diseases such as osteoporosis. Nevertheless, to attribute functional skeletal contributions of candidate genes to osteoporosis-related traits there is a need for efficient and cost-effective in vivo functional testing. This can be achieved through CRISPR-based reverse genetic screens, where phenotyping is traditionally performed in stable germline KO mutants. Read More

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Type 2 diabetes is causally associated with reduced serum osteocalcin: A genome-wide association and Mendelian randomization study.

J Bone Miner Res 2021 May 6. Epub 2021 May 6.

Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.

Recent advances indicate that bone and energy metabolism are closely related. However, little direct evidence on causality has been provided in humans. We aimed to assess the association of three bone-related biomarkers 25 hydroxyvitamin D (25OHD), parathyroid hormone (PTH) and osteocalcin (OCN) with several metabolic phenotypes, and investigate any causal relevance to the associations using a Mendelian randomization (MR) study. Read More

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A polymorphism in the promoter of FRAS1 is a candidate SNP associated with metastatic prostate cancer.

Prostate 2021 May 6. Epub 2021 May 6.

Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA.

Background: Inflammation and one of its mediators, NF-kappa B (NFκB), have been implicated in prostate cancer carcinogenesis. We assessed whether germline polymorphisms associated with NFκB are associated with the risk of developing lethal disease (metastases or death from prostate cancer).

Methods: Using a Bayesian approach leveraging NFκB biology with integration of publicly available datasets we used a previously defined genome-wide functional association network specific to NFκB and lethal prostate cancer. Read More

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Genome-wide association analysis for yield-related traits at the R6 stage in a Chinese soybean mini core collection.

Genes Genomics 2021 May 6. Epub 2021 May 6.

National Center for Soybean Improvement, Key Laboratory of Biology and Genetics and Breeding for Soybean, Ministry of Agriculture, State Key Laboratory for Crop Genetics and Germplasm Enhancement, College of Agriculture, Nanjing Agricultural University, Weigang No. 1, Nanjing, 210095, Jiangsu, China.

Background: Soybean (Glycine max (L.) Merr.) is an economically important crop for vegetable oil and protein production, and yield is a critical trait for grain/vegetable uses of soybean. Read More

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Metabolic source isotopic pair labeling and genome-wide association are complementary tools for the identification of metabolite-gene associations in plants.

Plant Cell 2021 May;33(3):492-510

Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.

The optimal extraction of information from untargeted metabolomics analyses is a continuing challenge. Here, we describe an approach that combines stable isotope labeling, liquid chromatography- mass spectrometry (LC-MS), and a computational pipeline to automatically identify metabolites produced from a selected metabolic precursor. We identified the subset of the soluble metabolome generated from phenylalanine (Phe) in Arabidopsis thaliana, which we refer to as the Phe-derived metabolome (FDM) In addition to identifying Phe-derived metabolites present in a single wild-type reference accession, the FDM was established in nine enzymatic and regulatory mutants in the phenylpropanoid pathway. Read More

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Genetic Meta-Analysis of Twin Birth Weight Shows High Genetic Correlation with Singleton Birth Weight.

Hum Mol Genet 2021 May 6. Epub 2021 May 6.

Department of Medical Epidemiology and Biostatististics, Karolinska Institutet, Stockholm, Sweden.

Birth weight (BW) is an important predictor of newborn survival and health and has associations with many adult health outcomes, including cardio-metabolic disorders, autoimmune diseases, and mental health. On average, twins have a lower BW than singletons as a result of a different pattern of fetal growth and shorter gestational duration. Therefore, investigations into the genetics of BW often exclude data from twins, leading to a reduction in sample size and remaining ambiguities concerning the genetic contribution to BW in twins. Read More

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Polygenic Scores for Cognitive Abilities and Their Association with Different Aspects of General Intelligence-A Deep Phenotyping Approach.

Mol Neurobiol 2021 May 5. Epub 2021 May 5.

Department of Biopsychology, Institute of Cognitive Neuroscience, Ruhr University Bochum, Bochum, Germany.

Intelligence is a highly polygenic trait and genome-wide association studies (GWAS) have identified thousands of DNA variants contributing with small effects. Polygenic scores (PGS) can aggregate those effects for trait prediction in independent samples. As large-scale light-phenotyping GWAS operationalized intelligence as performance in rather superficial tests, the question arises which intelligence facets are actually captured. Read More

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TeoNAM: A Nested Association Mapping Population for Domestication and Agronomic Trait Analysis in Maize.

Genetics 2019 Nov;213(3):1065-1078

Laboratory of Genetics, University of Wisconsin-Madison, Wisconsin 53706.

Recombinant inbred lines (RILs) are an important resource for mapping genes controlling complex traits in many species. While RIL populations have been developed for maize, a maize RIL population with multiple teosinte inbred lines as parents has been lacking. Here, we report a teosinte nested association mapping (TeoNAM) population, derived from crossing five teosinte inbreds to the maize inbred line W22. Read More

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November 2019

TeoNAM: A Nested Association Mapping Population for Domestication and Agronomic Trait Analysis in Maize.

Genetics 2019 Nov;213(3):1065-1078

Laboratory of Genetics, University of Wisconsin-Madison, Wisconsin 53706.

Recombinant inbred lines (RILs) are an important resource for mapping genes controlling complex traits in many species. While RIL populations have been developed for maize, a maize RIL population with multiple teosinte inbred lines as parents has been lacking. Here, we report a teosinte nested association mapping (TeoNAM) population, derived from crossing five teosinte inbreds to the maize inbred line W22. Read More

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November 2019

A New Polygenic Model for Nonfamilial Colorectal Cancer Inheritance Based on the Genetic Architecture of the Azoxymethane-Induced Mouse Model.

Genetics 2020 Mar;214(3):691-702

Department of Molecular and Cellular Medicine, Texas A&M University, College Station, Texas 77843.

The azoxymethane carcinogen model of non-familial colorectal cancer has been used in mice to identify six new susceptibility loci and confirm 18 of 24 previous detected susceptibility loci. Using a population-based approach, the genetic architecture of colon cancer.. Read More

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Efficient Algorithms for Calculating Epistatic Genomic Relationship Matrices.

Genetics 2020 Nov;216(3):651-669

The genomic relationship matrix plays a key role in the analysis of genetic diversity, genomic prediction, and genome-wide association studies. The epistatic genomic relationship matrix is a natural generalization of the classic genomic relationship matrix in the sense that it implicitly models the epistatic effects among all markers. Calculating the exact form of the epistatic relationship matrix requires high computational load, and is hence not feasible when the number of markers is large, or when high-degree of epistasis is in consideration. Read More

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November 2020

Retrospective Association Analysis of Longitudinal Binary Traits Identifies Important Loci and Pathways in Cocaine Use.

Genetics 2019 Dec;213(4):1225-1236

Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut 06520.

Longitudinal phenotypes have been increasingly available in genome-wide association studies (GWAS) and electronic health record-based studies for identification of genetic variants that influence complex traits over time. For longitudinal binary data, there remain significant challenges in gene mapping, including misspecification of the model for phenotype distribution due to ascertainment. Here, we propose L-BRAT (Longitudinal Binary-trait Retrospective Association Test), a retrospective, generalized estimating equation-based method for genetic association analysis of longitudinal binary outcomes. Read More

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December 2019

Retrospective Association Analysis of Longitudinal Binary Traits Identifies Important Loci and Pathways in Cocaine Use.

Genetics 2019 Dec;213(4):1225-1236

Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut 06520.

Longitudinal phenotypes have been increasingly available in genome-wide association studies (GWAS) and electronic health record-based studies for identification of genetic variants that influence complex traits over time. For longitudinal binary data, there remain significant challenges in gene mapping, including misspecification of the model for phenotype distribution due to ascertainment. Here, we propose L-BRAT (Longitudinal Binary-trait Retrospective Association Test), a retrospective, generalized estimating equation-based method for genetic association analysis of longitudinal binary outcomes. Read More

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December 2019

Two Synthetic 18-Way Outcrossed Populations of Diploid Budding Yeast with Utility for Complex Trait Dissection.

Genetics 2020 Jun;215(2):323-342

Department of Ecology and Evolutionary Biology, School of Biological Sciences, University of California, Irvine, California 92697-2525.

Advanced-generation multiparent populations (MPPs) are a valuable tool for dissecting complex traits, having more power than genome-wide association studies to detect rare variants and higher resolution than F2 linkage mapping. To extend the advantages of MPPs in budding yeast, we describe the creation and characterization of two outbred MPPs derived from 18 genetically diverse founding strains. We carried out de novo assemblies of the genomes of the 18 founder strains, such that virtually all variation segregating between these strains is known, and represented those assemblies as Santa Cruz Genome Browser tracks. Read More

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Signaling by AWC Olfactory Neurons Is Necessary for Caenorhabditis elegans' Response to Prenol, an Odor Associated with Nematode-Infected Insects.

Genetics 2020 Sep;216(1):145-157

Department of Nematology, University of California, Riverside, California 92521.

Chemosensation plays a role in the behaviors and life cycles of numerous organisms, including nematodes. Many guilds of nematodes exist, ranging from the free-living Caenorhabditis elegans to various parasitic species such as entomopathogenic nematodes (EPNs), which are parasites of insects. Despite ecological differences, previous research has shown that both EPNs and C. Read More

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September 2020

Natural Variation and Genetic Determinants of Caenorhabditis elegans Sperm Size.

Genetics 2019 Oct;213(2):615-632

Université Côte d'Azur, CNRS, Inserm, IBV, Nice 06100, France.

The diversity in sperm shape and size represents a powerful paradigm to understand how selection drives the evolutionary diversification of cell morphology. Experimental work on the sperm biology of the male-hermaphrodite nematode Caenorhabditis elegans has elucidated diverse factors important for sperm fertilization success, including the competitive superiority of larger sperm. Yet despite extensive research, the molecular mechanisms regulating C. Read More

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October 2019

Interpreting Coronary Artery Disease Risk Through Gene-Environment Interactions in Gene Regulation.

Genetics 2019 Oct;213(2):651-663

Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan 48201.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Epidemiological and genome-wide association studies have identified environmental and genetic risk factors for CVD. Using human vascular endothelial cells treated with dexamethasone, retinoic acid, caffeine, and selenium. Read More

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October 2019

Interpreting Coronary Artery Disease Risk Through Gene-Environment Interactions in Gene Regulation.

Genetics 2019 Oct;213(2):651-663

Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan 48201.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Epidemiological and genome-wide association studies have identified environmental and genetic risk factors for CVD. Using human vascular endothelial cells treated with dexamethasone, retinoic acid, caffeine, and selenium. Read More

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October 2019

Natural Variation and Genetic Determinants of Caenorhabditis elegans Sperm Size.

Genetics 2019 Oct;213(2):615-632

Université Côte d'Azur, CNRS, Inserm, IBV, Nice 06100, France.

The diversity in sperm shape and size represents a powerful paradigm to understand how selection drives the evolutionary diversification of cell morphology. Experimental work on the sperm biology of the male-hermaphrodite nematode Caenorhabditis elegans has elucidated diverse factors important for sperm fertilization success, including the competitive superiority of larger sperm. Yet despite extensive research, the molecular mechanisms regulating C. Read More

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October 2019

Inferring the Nature of Missing Heritability in Human Traits Using Data from the GWAS Catalog.

Genetics 2019 Jul;212(3):891-904

Departamento de Bioquímica, Genética e Inmunología, Universidade de Vigo, 36310, Spain.

Here, López-Cortegano and Caballero carried out a meta-analysis using records from a database of genome-wide studies in order to investigate the nature of missing heritability in humans... Read More

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