To identify susceptibility loci for classical Hodgkin's lymphoma (cHL), we conducted a genome-wide association study of 589 individuals with cHL (cases) and 5,199 controls with validation in four independent samples totaling 2,057 cases and 3,416 controls. We identified three new susceptibility loci at 2p16.1 (rs1432295, REL, odds ratio (OR) = 1.22, combined P = 1.91 × 10(-8)), 8q24.21 (rs2019960, PVT1, OR = 1.33, combined P = 1.26 × 10(-13)) and 10p14 (rs501764, GATA3, OR = 1.25, combined P = 7.05 × 10(-8)). Furthermore, we confirmed the role of the major histocompatibility complex in disease etiology by revealing a strong human leukocyte antigen (HLA) association (rs6903608, OR = 1.70, combined P = 2.84 × 10(-50)). These data provide new insight into the pathogenesis of cHL.
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http://dx.doi.org/10.1038/ng.696 | DOI Listing |
Sci Rep
January 2025
Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
Genome-wide association studies (GWAS) have detected several susceptibility variants for urinary bladder cancer, but how gene regulation affects disease development remains unclear. To extend GWAS findings, we conducted a transcriptome-wide association study (TWAS) using PrediXcan to predict gene expression levels in whole blood using genome-wide genotype data for 6180 bladder cancer cases and 5699 controls included in the database of Genotypes and Phenotypes (dbGaP). Logistic regression was used to estimate adjusted gene-level odds ratios (OR) per 1-standard deviation higher expression with 95% confidence intervals (CI) for bladder cancer risk.
View Article and Find Full Text PDFFEMS Microbiol Lett
January 2025
Rochester Institute of Technology, Thomas H. Gosnell School of Life Sciences, Rochester, NY, USA.
Commensal Neisseria are members of a healthy human oropharyngeal microbiome; however, they also serve as a reservoir of antimicrobial resistance for their pathogenic relatives. Despite their known importance as sources of novel genetic variation for pathogens, we still do not understand the full suite of resistance mutations commensal species can harbor. Here, we use in vitro selection to assess the mutations that emerge in response to ciprofloxacin selection in commensal Neisseria by passaging 4 replicates of 4 different species in the presence of a selective antibiotic gradient for 20 days; then categorized derived mutations with whole genome sequencing.
View Article and Find Full Text PDFZhong Nan Da Xue Xue Bao Yi Xue Ban
July 2024
Department of Nephrology, Third Xiangya Hospital, Central South University, Changsha 410013.
Objectives: Genetic factors play an important role in the pathogenesis of diabetic kidney disease (DKD). Studies have shown that gene polymorphism is associated with the pathogenesis of type 2 diabetes mellitus (T2DM), but its role in DKD remains unclear. This study aims to analyze the distribution of alleles and genotypes of gene in patients with T2DM, and investigate the association between genetic polymorphism and DKD susceptibility in T2DM patients, which may provide new ideas for the pathogenesis of DKD.
View Article and Find Full Text PDFCell Genom
January 2025
Curriculum in Bioinformatics and Computational Biology, University of North Carolina, Chapel Hill, NC 27599, USA; Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, NC 27599, USA; Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address:
Osteoarthritis (OA) poses a significant healthcare burden with limited treatment options. While genome-wide association studies (GWASs) have identified over 100 OA-associated loci, translating these findings into therapeutic targets remains challenging. To address this gap, we mapped gene expression, chromatin accessibility, and 3D chromatin structure in primary human articular chondrocytes in both resting and OA-mimicking conditions.
View Article and Find Full Text PDFPLoS One
January 2025
Washington University School of Medicine, NeuroGenomics and Informatics Center, St. Louis, MO, United States of America.
Case-only designs in longitudinal cohorts are a valuable resource for identifying disease-relevant genes, pathways, and novel targets influencing disease progression. This is particularly relevant in Alzheimer's disease (AD), where longitudinal cohorts measure disease "progression," defined by rate of cognitive decline. Few of the identified drug targets for AD have been clinically tractable, and phenotypic heterogeneity is an obstacle to both clinical research and basic science.
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