Hum Mol Genet
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-7236, USA.
Published: May 2012
Genome-wide association studies have identified susceptibility loci for esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis of all single-nucleotide polymorphisms (SNPs) that showed nominally significant P-values in two previously published genome-wide scans that included a total of 2961 ESCC cases and 3400 controls. The meta-analysis revealed five SNPs at 2q33 with P< 5 × 10(-8), and the strongest signal was rs13016963, with a combined odds ratio (95% confidence interval) of 1.29 (1.19-1.40) and P= 7.63 × 10(-10). An imputation analysis of 4304 SNPs at 2q33 suggested a single association signal, and the strongest imputed SNP associations were similar to those from the genotyped SNPs. We conducted an ancestral recombination graph analysis with 53 SNPs to identify one or more haplotypes that harbor the variants directly responsible for the detected association signal. This showed that the five SNPs exist in a single haplotype along with 45 imputed SNPs in strong linkage disequilibrium, and the strongest candidate was rs10201587, one of the genotyped SNPs. Our meta-analysis found genome-wide significant SNPs at 2q33 that map to the CASP8/ALS2CR12/TRAK2 gene region. Variants in CASP8 have been extensively studied across a spectrum of cancers with mixed results. The locus we identified appears to be distinct from the widely studied rs3834129 and rs1045485 SNPs in CASP8. Future studies of esophageal and other cancers should focus on comprehensive sequencing of this 2q33 locus and functional analysis of rs13016963 and rs10201587 and other strongly correlated variants.
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http://dx.doi.org/10.1093/hmg/dds029 | DOI Listing |
J Clin Immunol
November 2024
Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, Assistance Publique Hôpitaux de Paris (AP-HP), Paris, EU, France.
Purpose: CTLA4 deficiency is an inborn error of immunity (IEI) due to heterozygosity for germline loss-of-function variants of the CTLA4 gene located on chromosome 2q33.2. CTLA4 deficiency underlies pleiotropic immune and lymphoproliferation-mediated features with incomplete penetrance.
View Article and Find Full Text PDFNeurology
October 2024
From the Stroke Pharmacogenomics and Genetics Group (E.M., J.C.-M., L.L.-C., C.G.-F., N.C., M.L.L., J.M.M.-C., P.V.-G., I.F.-C.), Biomedical Research Institute Sant Pau (IIB SANT PAU); Epilepsy Unit (E.M., A.S.-M., V.R.-C.), Neurology Service, Hospital de la Santa Creu i Sant Pau, Barcelona; Stroke Pharmacogenomics and Genetics (N.C.), Fundació MútuaTerrassa per la Docència i la Recerca; and Department of Neurology (C.G.-F., A.A.-S., J.M.-F.), Hospital de la Santa Creu i Sant Pau, IIB SANT PAU, Barcelona, Spain.
Background And Objectives: Genome-wide association studies (GWASs) have only 2 loci associated with spontaneous intracerebral hemorrhage (ICH): for lobar and 1q22 for nonlobar ICH. We aimed to discover new loci through an analysis that combines correlated traits (multi-trait analysis of GWAS [MTAG]) and explore a gene-based analysis, transcriptome-wide association study (TWAS), and proteome-wide association study (PWAS) to understand the biological mechanisms of spontaneous ICH providing potential therapeutic targets.
Methods: We use the published MTAG of ICH (patients with spontaneous intraparenchymal bleeding) and small-vessel ischemic stroke.
Cancer Epidemiol Biomarkers Prev
September 2023
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, Victoria, Australia.
Neuro Oncol
July 2023
Centre of Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia.
Hum Mol Genet
November 2022
Department of Pediatrics, Keio University School of Medicine, Tokyo 1608582, Japan.
Congenital hypothyroidism due to thyroid dysgenesis (TD), presented as thyroid aplasia, hypoplasia or ectopia, is one of the most prevalent rare diseases with an isolated organ malformation. The pathogenesis of TD is largely unknown, although a genetic predisposition has been suggested. We performed a genome-wide association study (GWAS) with 142 Japanese TD cases and 8380 controls and found a significant locus at 2q33.
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