2,405 results match your criteria genome-wide framework


HIGH CROSSOVER RATE1 encodes PROTEIN PHOSPHATASE X1 and restricts meiotic crossovers in Arabidopsis.

Nat Plants 2021 Apr 12. Epub 2021 Apr 12.

Department of Plant Sciences, University of Cambridge, Cambridge, UK.

Meiotic crossovers are tightly restricted in most eukaryotes, despite an excess of initiating DNA double-strand breaks. The majority of plant crossovers are dependent on class I interfering repair, with a minority formed via the class II pathway. Class II repair is limited by anti-recombination pathways; however, similar pathways repressing class I crossovers have not been identified. Read More

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Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19.

Nat Med 2021 Apr 9. Epub 2021 Apr 9.

Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA, USA.

Drug repurposing provides a rapid approach to meet the urgent need for therapeutics to address COVID-19. To identify therapeutic targets relevant to COVID-19, we conducted Mendelian randomization analyses, deriving genetic instruments based on transcriptomic and proteomic data for 1,263 actionable proteins that are targeted by approved drugs or in clinical phase of drug development. Using summary statistics from the Host Genetics Initiative and the Million Veteran Program, we studied 7,554 patients hospitalized with COVID-19 and >1 million controls. Read More

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Prediction of biological age and evaluation of genome-wide dynamic methylomic changes throughout human aging.

G3 (Bethesda) 2021 Apr 7. Epub 2021 Apr 7.

Department of Animal and Dairy Sciences, University of Wisconsin-Madison, 53706, Madison, WI, USA.

The use of DNA methylation signatures to predict chronological age and aging rate is of interest in many fields, including disease prevention and treatment, forensics, and anti-aging medicine. Although a large number of methylation markers are significantly associated with age, most age-prediction methods use a few markers selected based on either previously published studies or datasets containing methylation information. Here, we implemented reproducing kernel Hilbert spaces (RKHS) regression and a ridge regression model in a Bayesian framework that utilized phenotypic and methylation profiles simultaneously to predict chronological age. Read More

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Causal effects of plasma lipids on the risk of atrial fibrillation: A multivariable mendelian randomization study.

Nutr Metab Cardiovasc Dis 2021 Feb 20. Epub 2021 Feb 20.

Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. Electronic address:

Background And Aims: Observational studies have suggested that plasma lipids contribute substantially to cardiovascular disease, but "cholesterol paradox" in atrial fibrillation (AF) remains. We sought to investigate the causal effects of lipid profiles on the risk of AF.

Methods And Results: Two-sample Mendelian randomization (MR) framework was implemented to examine the causality of association. Read More

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February 2021

Phenotypically independent profiles relevant to mental health are genetically correlated.

Transl Psychiatry 2021 Apr 1;11(1):202. Epub 2021 Apr 1.

NORMENT, KG Jebsen Centre for Neurodevelopmental Disorders, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Genome-wide association studies (GWAS) and family-based studies have revealed partly overlapping genetic architectures between various psychiatric disorders. Given clinical overlap between disorders, our knowledge of the genetic architectures underlying specific symptom profiles and risk factors is limited. Here, we aimed to derive distinct profiles relevant to mental health in healthy individuals and to study how these genetically relate to each other and to common psychiatric disorders. Read More

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The histone variant Sl_H2A.Z regulates carotenoid biosynthesis and gene expression during tomato fruit ripening.

Hortic Res 2021 Apr 1;8(1):85. Epub 2021 Apr 1.

Department of Horticulture, College of Horticulture and Plant Protection, Yangzhou University, 225009, Yangzhou, Jiangsu, China.

The conserved histone variant H2A.Z is essential for transcriptional regulation; defense responses; and various biological processes in plants, such as growth, development, and flowering. However, little is known about how H2A. Read More

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Genetic factors influencing a neurobiological substrate for psychiatric disorders.

Transl Psychiatry 2021 Mar 29;11(1):192. Epub 2021 Mar 29.

Institute of Neuroscience and Medicine (INM-1, INM-7), Research Centre Jülich, Jülich, Germany.

A retrospective meta-analysis of magnetic resonance imaging voxel-based morphometry studies proposed that reduced gray matter volumes in the dorsal anterior cingulate and the left and right anterior insular cortex-areas that constitute hub nodes of the salience network-represent a common substrate for major psychiatric disorders. Here, we investigated the hypothesis that the common substrate serves as an intermediate phenotype to detect genetic risk variants relevant for psychiatric disease. To this end, after a data reduction step, we conducted genome-wide association studies of a combined common substrate measure in four population-based cohorts (n = 2271), followed by meta-analysis and replication in a fifth cohort (n = 865). Read More

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Genome-wide identification and expression analysis of the B-box transcription factor gene family in grapevine (Vitis vinifera L.).

BMC Genomics 2021 Mar 29;22(1):221. Epub 2021 Mar 29.

State Key Laboratory of Crop Stress Biology in Arid Areas, College of Horticulture, Northwest A&F University, Yangling, 712100, Shaanxi, China.

Background: B-box (BBX) zinc-finger transcription factors play important roles in plant growth, development, and stress response. Although these proteins have been studied in model plants such as Arabidopsis thaliana or Oryza sativa, little is known about the evolutionary history or expression patterns of BBX proteins in grapevine (Vitis vinifera L.). Read More

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Polygenic risk for depression, anxiety and neuroticism are associated with the severity and rate of change in depressive symptoms across adolescence.

J Child Psychol Psychiatry 2021 Mar 28. Epub 2021 Mar 28.

MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.

Background: Adolescence marks a period where depression will commonly onset. Twin studies show that genetic influences play a role in how depression develops and changes across adolescence. Recent genome-wide association studies highlight that common genetic variants - which can be combined into polygenic risk scores (PRS) - are also implicated in depression. Read More

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Meta-analysis of genome-wide DNA methylation identifies shared associations across neurodegenerative disorders.

Genome Biol 2021 Mar 26;22(1):90. Epub 2021 Mar 26.

Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.

Background: People with neurodegenerative disorders show diverse clinical syndromes, genetic heterogeneity, and distinct brain pathological changes, but studies report overlap between these features. DNA methylation (DNAm) provides a way to explore this overlap and heterogeneity as it is determined by the combined effects of genetic variation and the environment. In this study, we aim to identify shared blood DNAm differences between controls and people with Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease. Read More

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Full-length ribosome density prediction by a multi-input and multi-output model.

PLoS Comput Biol 2021 Mar 26;17(3):e1008842. Epub 2021 Mar 26.

Institute for Interdisciplinary Information Sciences, Tsinghua University, Beijing, China.

Translation elongation is regulated by a series of complicated mechanisms in both prokaryotes and eukaryotes. Although recent advance in ribosome profiling techniques has enabled one to capture the genome-wide ribosome footprints along transcripts at codon resolution, the regulatory codes of elongation dynamics are still not fully understood. Most of the existing computational approaches for modeling translation elongation from ribosome profiling data mainly focus on local contextual patterns, while ignoring the continuity of the elongation process and relations between ribosome densities of remote codons. Read More

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Integrating disease and drug-related phenotypes for improved identification of pharmacogenomic variants.

Pharmacogenomics 2021 Mar 26. Epub 2021 Mar 26.

BC Children's Hospital Research Institute, Vancouver, BC, V5Z 4H4, Canada.

To improve the identification and interpretation of pharmacogenetic variants through the integration of disease and drug-related traits. We hypothesized that integrating genome-wide disease and pharmacogenomic data may drive new insights into drug toxicity and response by identifying shared genetic architecture. Pleiotropic variants were identified using a methodological framework incorporating colocalization analysis. Read More

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Pathway-level analysis of genome-wide circadian dynamics in diverse tissues in rat and mouse.

J Pharmacokinet Pharmacodyn 2021 Mar 25. Epub 2021 Mar 25.

Biomedical Engineering Department, Rutgers University, Piscataway, NJ, USA.

A computational framework is developed to enable the characterization of genome-wide, multi-tissue circadian dynamics at the level of "functional groupings of genes" defined in the context of signaling, cellular/genetic processing and metabolic pathways in rat and mouse. Our aim is to identify how individual genes come together to generate orchestrated rhythmic patterns and how these may vary within and across tissues. We focus our analysis on four tissues (adipose, liver, lung, and muscle). Read More

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MSA-Regularized Protein Sequence Transformer toward Predicting Genome-Wide Chemical-Protein Interactions: Application to GPCRome Deorphanization.

J Chem Inf Model 2021 Mar 23. Epub 2021 Mar 23.

Ph.D. Program in Computer Science, The Graduate Center, The City University of New York, New York, New York 10016, United States.

Small molecules play a critical role in modulating biological systems. Knowledge of chemical-protein interactions helps address fundamental and practical questions in biology and medicine. However, with the rapid emergence of newly sequenced genes, the endogenous or surrogate ligands of a vast number of proteins remain unknown. Read More

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SeqEnhDL: sequence-based classification of cell type-specific enhancers using deep learning models.

BMC Res Notes 2021 Mar 19;14(1):104. Epub 2021 Mar 19.

Division of Intramural Clinical and Biological Research (DICBR), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, 20892, USA.

Objective: To address the challenge of computational identification of cell type-specific regulatory elements on a genome-wide scale.

Results: We propose SeqEnhDL, a deep learning framework for classifying cell type-specific enhancers based on sequence features. DNA sequences of "strong enhancer" chromatin states in nine cell types from the ENCODE project were retrieved to build and test enhancer classifiers. Read More

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Incorporating European GWAS findings improve polygenic risk prediction accuracy of breast cancer among East Asians.

Genet Epidemiol 2021 Mar 19. Epub 2021 Mar 19.

Department of Molecular Physiology & Biophysics, Vanderbilt Genetics Institute, Vanderbilt University, Nashville, Tennessee, USA.

Previous genome-wide association studies (GWASs) have been largely focused on European (EUR) populations. However, polygenic risk scores (PRSs) derived from EUR have been shown to perform worse in non-EURs compared with EURs. In this study, we aim to improve PRS prediction in East Asians (EASs). Read More

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Estimating the effective sample size in association studies of quantitative traits.

G3 (Bethesda) 2021 Mar 18. Epub 2021 Mar 18.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

The effective sample size (ESS) is a metric used to summarize in a single term the amount of correlation in a sample. It is of particular interest when predicting the statistical power of genome-wide association studies (GWAS) based on linear mixed models. Here, we introduce an analytical form of the ESS for mixed-model GWAS of quantitative traits and relate it to empirical estimators recently proposed. Read More

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Gene-Environment Interaction: A Variable Selection Perspective.

Methods Mol Biol 2021 ;2212:191-223

Department of Statistics, Kansas State University, Manhattan, KS, USA.

Gene-environment interactions have important implications for elucidating the genetic basis of complex diseases beyond the joint function of multiple genetic factors and their interactions (or epistasis). In the past, G × E interactions have been mainly conducted within the framework of genetic association studies. The high dimensionality of G × E interactions, due to the complicated form of environmental effects and the presence of a large number of genetic factors including gene expressions and SNPs, has motivated the recent development of penalized variable selection methods for dissecting G × E interactions, which has been ignored in the majority of published reviews on genetic interaction studies. Read More

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Two-Stage Testing for Epistasis: Screening and Verification.

Methods Mol Biol 2021 ;2212:69-92

Radboudumc, Nijmegen, The Netherlands.

Undiscovered gene-to-gene interaction (epistasis) is a possible explanation for the "missing heritability" of complex traits and diseases. On a genome-wide scale, screening for epistatic effects among all possible pairs of genetic markers faces two main complications. Firstly, the classical statistical methods for modeling epistasis are computationally very expensive, which makes them impractical on such large scale. Read More

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Prioritization of schizophrenia risk genes from GWAS results by integrating multi-omics data.

Transl Psychiatry 2021 Mar 17;11(1):175. Epub 2021 Mar 17.

Department of Medical Research Center, Sun Yat-Sen Memorial Hospital, Guangzhou, China.

Schizophrenia (SCZ) is a polygenic disease with a heritability approaching 80%. Over 100 SCZ-related loci have so far been identified by genome-wide association studies (GWAS). However, the risk genes associated with these loci often remain unknown. Read More

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The Acute Stress Response in the Multiomic Era.

Biol Psychiatry 2021 Jan 13. Epub 2021 Jan 13.

Laboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zürich, Switzerland; Neuroscience Center Zurich, ETH Zurich and University of Zurich, Zürich, Switzerland. Electronic address:

Studying the stress response is a major pillar of neuroscience research not only because stress is a daily reality but also because the exquisitely fine-tuned bodily changes triggered by stress are a neuroendocrinological marvel. While the genome-wide changes induced by chronic stress have been extensively studied, we know surprisingly little about the complex molecular cascades triggered by acute stressors, the building blocks of chronic stress. The acute stress (or fight-or-flight) response mobilizes organismal energy resources to meet situational demands. Read More

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January 2021

Investigating Shared Genetic Basis Across Tourette Syndrome and Comorbid Neurodevelopmental Disorders Along the Impulsivity-Compulsivity Spectrum.

Biol Psychiatry 2021 Jan 8. Epub 2021 Jan 8.

Department of Biological Sciences, Purdue University, West Lafayette, Indiana. Electronic address:

Background: Tourette syndrome (TS) is often found comorbid with other neurodevelopmental disorders across the impulsivity-compulsivity spectrum, with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) as most prevalent. This points to the possibility of a common etiological thread along an impulsivity-compulsivity continuum.

Methods: Investigating the shared genetic basis across TS, ADHD, ASD, and OCD, we undertook an evaluation of cross-disorder genetic architecture and systematic meta-analysis, integrating summary statistics from the latest genome-wide association studies (93,294 individuals, 6,788,510 markers). Read More

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January 2021

An Integrated Framework Reinstating the Environmental Dimension for GWAS and Genomic Selection in Crops.

Mol Plant 2021 Mar 10. Epub 2021 Mar 10.

Department of Agronomy, Iowa State University, Ames, IA 50011, USA. Electronic address:

Identifying mechanisms and pathways involved in gene-environment interplay and phenotypic plasticity is a long-standing challenge. It is highly desirable to establish an integrated framework for complex trait dissection and prediction with an environmental dimension. A critical step was to identify an environmental index that is both biologically relevant and estimable for new environments. Read More

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Improving reporting standards for polygenic scores in risk prediction studies.

Nature 2021 Mar 10;591(7849):211-219. Epub 2021 Mar 10.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Polygenic risk scores (PRSs), which often aggregate results from genome-wide association studies, can bridge the gap between initial discovery efforts and clinical applications for the estimation of disease risk using genetics. However, there is notable heterogeneity in the application and reporting of these risk scores, which hinders the translation of PRSs into clinical care. Here, in a collaboration between the Clinical Genome Resource (ClinGen) Complex Disease Working Group and the Polygenic Score (PGS) Catalog, we present the Polygenic Risk Score Reporting Standards (PRS-RS), in which we update the Genetic Risk Prediction Studies (GRIPS) Statement to reflect the present state of the field. Read More

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Deep learning-based enhancement of epigenomics data with AtacWorks.

Nat Commun 2021 03 8;12(1):1507. Epub 2021 Mar 8.

Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.

ATAC-seq is a widely-applied assay used to measure genome-wide chromatin accessibility; however, its ability to detect active regulatory regions can depend on the depth of sequencing coverage and the signal-to-noise ratio. Here we introduce AtacWorks, a deep learning toolkit to denoise sequencing coverage and identify regulatory peaks at base-pair resolution from low cell count, low-coverage, or low-quality ATAC-seq data. Models trained by AtacWorks can detect peaks from cell types not seen in the training data, and are generalizable across diverse sample preparations and experimental platforms. Read More

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A Hi-C data-integrated model elucidates E. coli chromosome's multiscale organization at various replication stages.

Nucleic Acids Res 2021 04;49(6):3077-3091

Tata Institute of Fundamental Research, Centre for Interdisciplinary Sciences, Hyderabad 500046, India.

The chromosome of Escherichia coli is riddled with multi-faceted complexity. The emergence of chromosome conformation capture techniques are providing newer ways to explore chromosome organization. Here we combine a beads-on-a-spring polymer-based framework with recently reported Hi-C data for E. Read More

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A scalable unified framework of total and allele-specific counts for cis-QTL, fine-mapping, and prediction.

Nat Commun 2021 03 3;12(1):1424. Epub 2021 Mar 3.

Section of Genetic Medicine, The University of Chicago, Chicago, IL, USA.

Genetic studies of the transcriptome help bridge the gap between genetic variation and phenotypes. To maximize the potential of such studies, efficient methods to identify expression quantitative trait loci (eQTLs) and perform fine-mapping and genetic prediction of gene expression traits are needed. Current methods that leverage both total read counts and allele-specific expression to identify eQTLs are generally computationally intractable for large transcriptomic studies. Read More

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Association of Genetic Variants With Migraine Subclassified by Clinical Symptoms in Adult Females.

Front Neurol 2020 12;11:617472. Epub 2021 Feb 12.

Harvard Medical School, Boston, MA, United States.

Migraine is heritable and formally diagnosed by structured criteria that require presence of some but not all possible migraine symptoms which include aura, several distinct manifestations of pain, nausea/vomiting, and sensitivity to light or sound. The most recent genome-wide genetic association study (GWAS) for migraine identified 38 loci. We investigated whether 46 single-nucleotide polymorphisms (SNPs), i. Read More

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February 2021

Shared genetic links between amyotrophic lateral sclerosis and obesity-related traits: a genome-wide association study.

Neurobiol Aging 2021 Feb 3. Epub 2021 Feb 3.

Department of Neurology, Laboratory of Neurodegenerative Disorders, National Clinical Research Center for Geriatric, West China Hospital, Sichuan University, Chengdu, 610041 China. Electronic address:

Epidemiological and clinical studies have suggested comorbidities between amyotrophic lateral sclerosis (ALS) and obesity-related traits. However, little is known about their shared genetic architecture. To examine whether genetic enrichment exists between ALS and obesity-related traits and to identify shared risk loci, we analyzed summary statistics from genome-wide association studies using the conditional false discovery rate statistical framework, and further conducted functional enrichment analysis. Read More

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February 2021