14,102 results match your criteria evidence genome-wide


Patterns of MHC-dependent sexual selection in a free-living population of sheep.

Mol Ecol 2021 May 7. Epub 2021 May 7.

Institute of Evolutionary Biology, University of Edinburgh.

The MHC is one of the most polymorphic gene clusters in vertebrates and play an essential role in adaptive immunity. Apart from pathogen-mediated selection, sexual selection can also contribute to the maintenance of MHC diversity. MHC-dependent sexual selection could occur via several mechanisms but at present there is no consensus as to which of these mechanisms are involved and their importance. 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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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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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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Extending Tests of Hardy-Weinberg Equilibrium to Structured Populations.

Genetics 2019 Nov;213(3):759-770

Lewis-Sigler Institute for Integrative Genomics, Princeton University, New Jersey 08544.

Testing for Hardy-Weinberg Equilibrium (HWE) is an important component in almost all analyses of population genetic data. Genetic markers that violate HWE are often treated as special cases; for example, they may be flagged as possible.. Read More

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November 2019

Extending Tests of Hardy-Weinberg Equilibrium to Structured Populations.

Genetics 2019 Nov;213(3):759-770

Lewis-Sigler Institute for Integrative Genomics, Princeton University, New Jersey 08544.

Testing for Hardy-Weinberg Equilibrium (HWE) is an important component in almost all analyses of population genetic data. Genetic markers that violate HWE are often treated as special cases; for example, they may be flagged as possible.. Read More

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November 2019

Deciphering Sex-Specific Genetic Architectures Using Local Bayesian Regressions.

Genetics 2020 May;215(1):231-241

Departments of Epidemiology and Biostatistics and Statistics and Probability, Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, Michigan, 48824.

Many complex human traits exhibit differences between sexes. While numerous factors likely contribute to this phenomenon, growing evidence from genome-wide studies suggest a partial explanation: that males and females from the same population possess differing genetic architectures. Despite this, mapping gene-by-sex (G×S) interactions remains a challenge likely because the magnitude of such an interaction is typically and exceedingly small; traditional genome-wide association techniques may be underpowered to detect such events, due partly to the burden of multiple test correction. Read More

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The relationship between cannabis and schizophrenia: a genetically informed perspective.

Addiction 2021 May 5. Epub 2021 May 5.

Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.

Background And Aims: While epidemiologic studies support a role for heavy, high-potency cannabis use on first episode psychosis, genetic models of causation suggest reverse causal effects of schizophrenia on cannabis use liability. We estimated the genetic relationship between cannabis use disorder (CUD) and schizophrenia (SCZ) and tested whether liability for CUD is causally associated with increased liability to SCZ while adjusting for tobacco smoking.

Design: This study used summary statistics from published genome-wide association studies (GWAS). Read More

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Comparison of adaptive multiple phenotype association tests using summary statistics in genome-wide association studies.

Hum Mol Genet 2021 May 5. Epub 2021 May 5.

Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27516 USA.

Genome-wide association studies have been successful mapping loci for individual phenotypes, but few studies have comprehensively interrogated evidence of shared genetic effects across multiple phenotypes simultaneously. Statistical methods have been proposed for analyzing multiple phenotypes using summary statistics, which enables studies of shared genetic effects while avoiding challenges associated with individual-level data sharing. Adaptive tests have been developed to maintain power against multiple alternative hypotheses because the most powerful single-alternative test depends on the underlying structure of the associations between the multiple phenotypes and a single nucleotide polymorphism (SNP). Read More

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Genetically determined elevated C-reactive protein associated with primary colorectal cancer risk: Mendelian randomization with lifestyle interactions.

Am J Cancer Res 2021 15;11(4):1733-1753. Epub 2021 Apr 15.

Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles, CA 90095, USA.

Systemic inflammation-related etiologic pathways via inflammatory cytokines in the development of colorectal cancer (CRC) have not been convincingly determined and may be confounded by lifestyle factors or reverse causality. We investigated the genetically predicted C-reactive protein (CRP) phenotype in the potential causal pathway of primary CRC risk in postmenopausal women in a Mendelian randomization (MR) framework. We employed individual-level data of the Women's Health Initiative Database for Genotypes and Phenotypes Study, which consists of 5 genome-wide association (GWA) studies, including 10,142 women, 737 of whom developed primary CRC. Read More

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Genome-Wide Analysis Identified a Set of Conserved lncRNAs Associated with Domestication-Related Traits in Rice.

Int J Mol Sci 2021 Apr 29;22(9). Epub 2021 Apr 29.

Guangdong Provincial Key Laboratory of Plant Resources, State Key Laboratory for Biocontrol, School of Life Science, Sun Yat-Sen University, Guangzhou 510275, China.

Crop domestication, which gives rise to a number of desirable agronomic traits, represents a typical model system of plant evolution. Numerous genomic evidence has proven that noncoding RNAs such as microRNAs and phasiRNAs, as well as protein-coding genes, are selected during crop domestication. However, limited data shows plant long noncoding RNAs (lncRNAs) are also involved in this biological process. Read More

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Investigating Olfactory Gene Variation and Odour Identification in Older Adults.

Genes (Basel) 2021 Apr 29;12(5). Epub 2021 Apr 29.

Centre for Healthy Brain Ageing, Faculty of Medicine, School of Psychiatry, University of New South Wales (UNSW), Sydney, NSW 2031, Australia.

Ageing is associated with a decrease in odour identification. Additionally, deficits in olfaction have been linked to age-related disease and mortality. Heritability studies suggest genetic variation contributes to olfactory identification. Read More

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Vulture genomes reveal molecular adaptations underlying obligate scavenging and low levels of genetic diversity.

Mol Biol Evol 2021 May 3. Epub 2021 May 3.

Department of Ecology, Tibetan Centre for Ecology and Conservation at WHU-TU, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan 430072, China.

Obligate scavenging on dead and decaying animal matter is a rare dietary specialization that in extant vertebrates is restricted to vultures. These birds perform essential ecological services, yet many vulture species have undergone recent steep population declines and are now endangered. To test for molecular adaptations underlying obligate scavenging in vultures, and to assess whether genomic features might have contributed to their population declines, we generated high-quality genomes of the Himalayan and bearded vultures, representing both independent origins of scavenging within the Accipitridae, alongside a sister taxon, the upland buzzard. Read More

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Rampant genome-wide admixture across the Heliconius radiation.

Genome Biol Evol 2021 May 4. Epub 2021 May 4.

Smithsonian Tropical Research Institute, Gamboa, Panama.

How frequent is gene flow between species? The pattern of evolution is typically portrayed as a phylogenetic tree, yet gene flow between good species may be an important mechanism in diversification, spreading adaptive traits and leading to a complex pattern of phylogenetic incongruence. This process has thus far been studied mainly among a few closely related species, or in geographically restricted areas such as islands, but not on the scale of a continental radiation. Using a nearly complete genomic representation of 47 species in the genus, we demonstrate that admixture has played a role throughout the evolution of the charismatic Neotropical butterflies Heliconius. Read More

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Learning a genome-wide score of human-mouse conservation at the functional genomics level.

Nat Commun 2021 05 3;12(1):2495. Epub 2021 May 3.

Bioinformatics Interdepartmental Program, University of California, Los Angeles, CA, USA.

Identifying genomic regions with functional genomic properties that are conserved between human and mouse is an important challenge in the context of mouse model studies. To address this, we develop a method to learn a score of evidence of conservation at the functional genomics level by integrating information from a compendium of epigenomic, transcription factor binding, and transcriptomic data from human and mouse. The method, Learning Evidence of Conservation from Integrated Functional genomic annotations (LECIF), trains neural networks to generate this score for the human and mouse genomes. Read More

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Detecting Gene-Environment Interaction for Maternal Exposures Using Case-Parent Trios Ascertained Through a Case With Non-Syndromic Orofacial Cleft.

Front Cell Dev Biol 2021 16;9:621018. Epub 2021 Apr 16.

Department of Epidemiology, School of Public Health, Johns Hopkins University, Baltimore, MD, United States.

Two large studies of case-parent trios ascertained through a proband with a non-syndromic orofacial cleft (OFC, which includes cleft lip and palate, cleft lip alone, or cleft palate alone) were used to test for possible gene-environment (G × E) interaction between genome-wide markers (both observed and imputed) and self-reported maternal exposure to smoking, alcohol consumption, and multivitamin supplementation during pregnancy. The parent studies were as follows: GENEVA, which included 1,939 case-parent trios recruited largely through treatment centers in Europe, the United States, and Asia, and 1,443 case-parent trios from the Pittsburgh Orofacial Cleft Study (POFC) also ascertained through a proband with an OFC including three major racial/ethnic groups (European, Asian, and Latin American). Exposure rates to these environmental risk factors (maternal smoking, alcohol consumption, and multivitamin supplementation) varied across studies and among racial/ethnic groups, creating substantial differences in power to detect G × E interaction, but the trio design should minimize spurious results due to population stratification. Read More

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Individual Differences in Intertemporal Choice.

Front Psychol 2021 16;12:643670. Epub 2021 Apr 16.

Department of Psychology, University of Bonn, Bonn, Germany.

Intertemporal choice involves deciding between smaller, sooner and larger, later rewards. People tend to prefer smaller rewards that are available earlier to larger rewards available later, a phenomenon referred to as temporal or delay discounting. Despite its ubiquity in human and non-human animals, temporal discounting is subject to considerable individual differences. Read More

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Impact of serum calcium levels on total body bone mineral density: A mendelian randomization study in five age strata.

Clin Nutr 2021 Mar 25;40(5):2726-2733. Epub 2021 Mar 25.

Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, 100069, China; Key Laboratory of Cerebral Microcirculation in Universities of Shandong, Department of Neurology, Second Affiliated Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, 271000, Shandong, China; National Engineering Laboratory of Internet Medical Diagnosis and Treatment Technology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China; Beijing Key Laboratory of Hypoxia Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China. Electronic address:

Background & Aims: Mendelian randomization (MR) studies have reported the causal association between serum calcium levels and bone mineral density (BMD). The results showed that genetically increased serum calcium levels in individuals with normal calcium levels did not increase BMD and could even reduce BMD. However, whether there are differences in the association between serum calcium and BMD in different age strata remains unclear. Read More

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Assembly and characterization of the genome of chard (Beta vulgaris ssp. vulgaris var. cicla).

J Biotechnol 2021 Apr 28. Epub 2021 Apr 28.

Institute of Computational Biology, Department of Biotechnology, University of Life Sciences and Natural Resources, Vienna (BOKU), Muthgasse 18, 1190, Vienna, Austria. Electronic address:

Chard (Beta vulgaris ssp. vulgaris var. cicla) is a member of one of four different cultigroups of beets. Read More

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Ongoing controversies and recent insights of the ARMS2-HTRA1 locus in age-related macular degeneration.

Exp Eye Res 2021 Apr 27:108605. Epub 2021 Apr 27.

Age-related macular degeneration (AMD) is the most common cause of central vision loss among elderly populations in industrialized countries. Genome-wide association studies have consistently associated two genomic loci with progression to late-stage AMD: the complement factor H (CFH) locus on chromosome 1q31 and the age-related maculopathy susceptibility 2-HtrA serine peptidase 1 (ARMS2-HTRA1) locus on chromosome 10q26. While the CFH risk variant has been shown to alter complement activity, the ARMS2-HTRA1 risk haplotype remains enigmatic due to high linkage disequilibrium and inconsistent functional findings spanning two genes that are plausibly causative for AMD risk. Read More

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Protective genes and pathways in Alzheimer's disease: moving towards precision interventions.

Mol Neurodegener 2021 04 29;16(1):29. Epub 2021 Apr 29.

Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, 1207 17th Ave S, Nashville, TN, 37212, USA.

Alzheimer's disease (AD) is a progressive, neurodegenerative disorder that is characterized by neurodegeneration, cognitive impairment, and an eventual inability to perform daily tasks. The etiology of Alzheimer's is complex, with numerous environmental and genetic factors contributing to the disease. Late-onset AD is highly heritable (60 to 80%), and over 40 risk loci for AD have been identified via large genome-wide association studies, most of which are common variants with small effect sizes. Read More

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Common Variation in Cytoskeletal Genes is Associated with Conotruncal Heart Defects.

Genes (Basel) 2021 Apr 27;12(5). Epub 2021 Apr 27.

Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, TX 77030, USA.

There is strong evidence for a genetic contribution to non-syndromic congenital heart defects (CHDs). However, exome- and genome-wide studies conducted at the variant and gene-level have identified few genome-wide significant CHD-related genes. Gene-set analyses are a useful complement to such studies and candidate gene-set analyses of rare variants have provided insight into the genetics of CHDs. Read More

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Identification and Expression Analysis of / Gene Family in L.

Int J Mol Sci 2021 Apr 28;22(9). Epub 2021 Apr 28.

College of Natural Resource and Environment, Northwest A&F University, Yangling 712100, China.

Slow type anion channels (SLAC/SLAHs) play important roles during anion transport, growth and development, abiotic stress responses and hormone responses in plants. However, there is few report on SLAC/SLAHs in rapeseed (). Genome-wide identification and expression analysis of / gene family members were performed in . Read More

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Genome-Wide Chromatin Analysis of FFPE Tissues Using a Dual-Arm Robot with Clinical Potential.

Cancers (Basel) 2021 Apr 28;13(9). Epub 2021 Apr 28.

Division of Molecular Modification and Cancer Biology, National Cancer Center Research Institute, Tokyo 104-0045, Japan.

Although chromatin immunoprecipitation and next-generation sequencing (ChIP-seq) using formalin-fixed paraffin-embedded tissue (FFPE) has been reported, it remained elusive whether they retained accurate transcription factor binding. Here, we developed a method to identify the binding sites of the insulator transcription factor CTCF and the genome-wide distribution of histone modifications involved in transcriptional activation. Importantly, we provide evidence that the ChIP-seq datasets obtained from FFPE samples are similar to or even better than the data for corresponding fresh-frozen samples, indicating that FFPE samples are compatible with ChIP-seq analysis. Read More

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Cystic Fibrosis Lung Disease Modifiers and Their Relevance in the New Era of Precision Medicine.

Genes (Basel) 2021 Apr 13;12(4). Epub 2021 Apr 13.

Department of Paediatric Respiratory Medicine, Royal Brompton and Harefield Hospitals, London SW3 6NP, UK.

Our understanding of cystic fibrosis (CF) has grown exponentially since the discovery of the cystic fibrosis transmembrane conductance regulator () gene in 1989. With evolving genetic and genomic tools, we have come to better understand the role of genotypes in the pathophysiology of the disease. This, in turn, has paved the way for the development of modulator therapies targeted at mutations in the , which are arguably one of the greatest advances in the treatment of CF. Read More

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Genome-Wide Transcriptional Analysis and Functional Validation Linked a Cluster of Epsilon Glutathione S-Transferases with Insecticide Resistance in the Major Malaria Vector across Africa.

Genes (Basel) 2021 Apr 13;12(4). Epub 2021 Apr 13.

LSTM Research Unit, Centre for Research in Infectious Diseases (CRID), Yaoundé P.O. Box 13591, Cameroon.

Resistance is threatening the effectiveness of insecticide-based interventions in use for malaria control. Pinpointing genes associated with resistance is crucial for evidence-based resistance management targeting the major malaria vectors. Here, a combination of RNA-seq based genome-wide transcriptional analysis and RNA-silencing in vivo functional validation were used to identify key insecticide resistance genes associated with DDT and DDT/permethrin cross-resistance across Africa. Read More

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Functional Genomic Analyses of the 21q22.3 Locus Identifying Functional Variants and Candidate Gene for Breast Cancer Risk.

Cancers (Basel) 2021 Apr 23;13(9). Epub 2021 Apr 23.

Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Department of Medicine, Division of Epidemiology, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.

We previously identified a locus at 21q22.3, tagged by the single nucleotide polymorphism (SNP) rs35418111, being associated with breast cancer risk at a genome-wide significance level; however, the underlying causal functional variants and gene(s) responsible for this association are unknown. We performed functional genomic analyses to identify potential functional variants and target genes that may mediate this association. Read More

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Genome-Wide Methylation Mapping Using Nanopore Sequencing Technology Identifies Novel Tumor Suppressor Genes in Hepatocellular Carcinoma.

Int J Mol Sci 2021 Apr 11;22(8). Epub 2021 Apr 11.

Institut fuer Zellbiochemie, OE4310, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30623 Hannover, Germany.

Downregulation of multiple tumor suppressor genes (TSGs) plays an important role in cancer formation. Recent evidence has accumulated that cancer progression involves genome-wide alteration of epigenetic modifications, which may cause downregulation of the tumor suppressor gene. Using hepatocellular carcinoma (HCC) as a system, we mapped 5-methylcytosine signal at a genome-wide scale using nanopore sequencing technology to identify novel TSGs. Read More

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