Abstract:
: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.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Abnet CC,Wang Z,Song X,Hu N,Zhou FY,Freedman ND,Li XM,Yu K,Shu XO,Yuan JM,Zheng W,Dawsey SM,Liao LM,Lee MP,Ding T,Qiao YL,Gao YT,Koh WP,Xiang YB,Tang ZZ,Fan JH,Chung CC,Wang C,Wheeler W,Yeager M,Yuengerdoi
10.1093/hmg/dds029subject
Has Abstractpub_date
2012-05-01 00:00:00pages
2132-41issue
9eissn
0964-6906issn
1460-2083pii
dds029journal_volume
21pub_type
杂志文章,meta分析abstract::Actinic keratosis (AK) is a pre-malignant skin disease, highly prevalent in elderly Europeans. This study investigates genetic susceptibility to AK with a genome-wide association study (GWAS). A full body skin examination was performed in 3194 elderly individuals from the Rotterdam Study (RS) of exclusive north-wester...
journal_title:Human molecular genetics
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journal_title:Human molecular genetics
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journal_title:Human molecular genetics
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journal_title:Human molecular genetics
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journal_title:Human molecular genetics
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journal_title:Human molecular genetics
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journal_title:Human molecular genetics
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journal_title:Human molecular genetics
pub_type: 杂志文章,评审
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journal_title:Human molecular genetics
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journal_title:Human molecular genetics
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.13.2121
更新日期:1998-12-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.12.1477
更新日期:2002-06-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu310
更新日期:2014-11-15 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.6.711
更新日期:1993-06-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.5.895
更新日期:1995-05-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/9.13.2009
更新日期:2000-08-12 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu006
更新日期:2014-06-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn132
更新日期:2008-08-01 00:00:00
abstract::Pseudoachondroplasia (PSACH) is one of the more common skeletal dysplasias and results from mutations in cartilage oligomeric matrix protein (COMP). Most COMP mutations identified to date cluster in the TSP3 repeat region of COMP and the mutant protein is retained in the rough endoplasmic reticulum (rER) of chondrocyt...
journal_title:Human molecular genetics
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journal_title:Human molecular genetics
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更新日期:2021-01-21 00:00:00
abstract::Huntington's disease (HD) is caused by an expansion of a poly glutamine (polyQ) stretch in the huntingtin protein (HTT) that is necessary to cause pathology and formation of HTT aggregates. Here we ask whether expanded polyQ is sufficient to cause pathology and aggregate formation. By addressing the sufficiency questi...
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pub_type: 杂志文章,评审
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journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:2018-10-01 00:00:00
abstract::Osteoarthritis is a common, complex disease with no curative therapy. In this review, we summarize current knowledge on disease aetiopathogenesis and outline genetics and genomics approaches that are helping catalyse a much-needed improved understanding of the biological underpinning of disease development and progres...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
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更新日期:2017-10-01 00:00:00
abstract::Machado-Joseph disease (MJD) is a fatal, dominant neurodegenerative disorder. MJD results from polyglutamine repeat expansion in the MJD-1 gene, conferring a toxic gain of function to the ataxin-3 protein. In this study, we aimed at overexpressing ataxin-3 in the rat brain using lentiviral vectors (LV), to generate an...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn106
更新日期:2008-07-15 00:00:00
abstract::Congenital heart defects comprise the most common form of major birth defects, affecting 0.7% of all newborn infants. Jacobsen syndrome (11q-) is a rare chromosomal disorder caused by deletions in distal 11q. We have previously determined that a wide spectrum of the most common congenital heart defects occur in 11q-, ...
journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:2010-02-15 00:00:00
abstract::Mutations in the ORF15 exon of the RPGR gene cause a common form of X-linked retinitis pigmentosa, which often results in severe loss of vision. In dogs and mice, gene augmentation therapy has been shown to arrest the progressive degeneration of rod and cone photoreceptors. However, the distribution of potentially tre...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw361
更新日期:2016-12-15 00:00:00
abstract::Huntington's disease (HD) is caused by a polyglutamine expansion mutation in the huntingtin protein that confers a toxic gain-of-function and causes the protein to become aggregate-prone. Aggregate-prone proteins are cleared by macroautophagy, and upregulating this process by rapamycin, which inhibits the mammalian ta...
journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:2008-01-15 00:00:00
abstract::Mucopolysaccharidosis type VI (MPS-VI), caused by mutational inactivation of the glycosaminoglycan-degrading enzyme arylsulfatase B (Arsb), is a lysosomal storage disorder primarily affecting the skeleton. We have previously reported that Arsb-deficient mice display high trabecular bone mass and impaired skeletal grow...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa006
更新日期:2020-03-27 00:00:00
abstract::Schizophrenia may arise from subtle abnormalities in brain development due to alterations in the functions of candidate susceptibility genes such as Disrupted-in-schizophrenia 1 (DISC1) and Neuregulin 1 (NRG1). To provide novel insights into the functions of DISC1 in brain development, we mapped the expression of zebr...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn361
更新日期:2009-02-01 00:00:00