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  • Wang, Zhaoming, et al. (författare)
  • Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
  • 2014
  • Ingår i: ; 23:24, s. 6616-6633
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
  • Arokiasamy, Perianayagam, et al. (författare)
  • Chronic Noncommunicable Diseases in 6 Low-and Middle-Income Countries : Findings From Wave 1 of the World Health Organization's Study on Global Ageing and Adult Health (SAGE)
  • 2017
  • Ingår i: American Journal of Epidemiology. - 0002-9262 .- 1476-6256. ; 185:6, s. 414-428
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper, we examine patterns of self-reported diagnosis of noncommunicable diseases (NCDs) and prevalences of algorithm/measured test-based, undiagnosed, and untreated NCDs in China, Ghana, India, Mexico, Russia, and South Africa. Nationally representative samples of older adults aged >= 50 years were analyzed from wave 1 of the World Health Organization's Study on Global Ageing and Adult Health (2007-2010; n = 34,149). Analyses focused on 6 conditions: angina, arthritis, asthma, chronic lung disease, depression, and hypertension. Outcomes for these NCDs were: 1) self-reported disease, 2) algorithm/measured test-based disease, 3) undiagnosed disease, and 4) untreated disease. Algorithm/measured test-based prevalence of NCDs was much higher than self-reported prevalence in all 6 countries, indicating underestimation of NCD prevalence in low-and middle-income countries. Undiagnosed prevalence of NCDs was highest for hypertension, ranging from 19.7% (95% confidence interval (CI): 18.1, 21.3) in India to 49.6% (95% CI: 46.2, 53.0) in South Africa. The proportion untreated among all diseases was highest for depression, ranging from 69.5% (95% CI: 57.1, 81.9) in South Africa to 93.2% (95% CI: 90.1, 95.7) in India. Higher levels of education and wealth significantly reduced the odds of an undiagnosed condition and untreated morbidity. A high prevalence of undiagnosed NCDs and an even higher proportion of untreated NCDs highlights the inadequacies in diagnosis and management of NCDs in local health-care systems.
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