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Genome-wide association studies (GWAS) have discovered many risk variants for type 2 diabetes. However, estimates of the contributions of risk variants to type 2 diabetes predisposition are often based on highly selected case-control samples, and reliable estimates of population-level effect sizes are missing, especially in non-European populations.
The individual and cumulative effects of 59 established type 2 diabetes risk loci were measured in a population-based China Kadoorie Biobank (CKB) study of 93,000 Chinese adults, including >7,100 diabetes cases.
Association signals were directionally consistent between CKB and the original discovery GWAS: of 56 variants passing quality control, 48 showed the same direction of effect (binomial test, p = 2.3 × 10−8). We observed a consistent overall trend towards lower risk variant effect sizes in CKB than in case-control samples of GWAS meta-analyses (mean 19-22% decrease in log odds, p ≤ 0.0048), likely to reflect correction of both ‘winner’s curse’ and spectrum bias effects. The association with risk of diabetes of a genetic risk score, based on lead variants at 25 loci considered to act through beta cell function, demonstrated significant interactions with several measures of adiposity (BMI, waist circumference [WC], WHR and percentage body fat [PBF]; all pinteraction < 1 × 10−4), with a greater effect being observed in leaner adults. Conclusions/interpretation Our study provides further evidence of shared genetic architecture for type 2 diabetes between Europeans and East Asians. It also indicates that even very large GWAS meta-analyses may be vulnerable to substantial inflation of effect size estimates, compared with those observed in large-scale population-based cohort studies. Access to research materials Details of how to access China Kadoorie Biobank data and details of the data release schedule are available from www.ckbiobank.org/site/Data+Access. Electronic supplementary material The online version of this article (doi:10.1007/s00125-016-3920-9) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
Biobank, Chinese, Genetic risk score, Population-based cohort studies, Type 2 diabetes, Winner’s curse
Evaluation of type 2 diabetes genetic risk variants in Chinese adults: findings from 93,000 individuals from the China Kadoorie Biobank
Wei Gan, Robin G. Walters, Michael V. Holmes, Fiona Bragg, Iona Y. Millwood, Karina Banasik, Yiping Chen, Huaidong Du, Andri Iona, Anubha Mahajan, Ling Yang, Zheng Bian, Yu Guo, Robert J. Clarke, Liming Li, Mark I. McCarthy,corresponding author Zhengming Chen,corresponding author and on behalf of the China Kadoorie Biobank Collaborative Group
Vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous VISA (hVISA) are associated with vancomycin treatment failure, and are becoming an increasing public health problem. Therefore, we undertook this study of 91 published studies and made subgroup comparisons of hVISA/VISA incidence in different study years, locations, and types of clinical samples. We also analyzed the genetic backgrounds of these strains.
A systematic literature review of relevant articles published in PubMed and EMBASE from January 1997 to August 2014 was conducted. We selected and assessed journal articles reporting the prevalence rates of hVISA/VISA.
The pooled prevalence of hVISA was 6.05% in 99,042 methicillin-resistant S. aureus (MRSA) strains and that of VISA was 3.01% in 68,792 MRSA strains. The prevalence of hVISA was 4.68% before 2006, 5.38% in 2006-2009, and 7.01% in 2010-2014. VISA prevalence was 2.05%, 2.63%, and 7.93%, respectively. In a subgroup analysis of different isolation locations, the prevalence of hVISA strains was 6.81% in Asia and 5.60% in Europe/America, and that of VISA was 3.42% and 2.75%, respectively. The frequencies of hVISA isolated from blood culture samples and from all clinical samples were 9.81% and 4.68%, respectively, and those of VISA were 2.00% and 3.07%, respectively. The most prevalent genotype was staphylococcal cassette chromosome mec (SCCmec) II, which accounted for 48.16% and 37.74% of hVISA and VISA, respectively. Sequence Type (ST) 239 was most prevalent.
The prevalence of hVISA/VISA has been increasing in recent years, but has been grossly underestimated. Its incidence is higher in Asia than in Europe/America. hVISA is isolated from blood culture samples more often than from other samples. These strains are highly prevalent in epidemic MRSA strains. This study clarifies the epidemiology of hVISA/VISA and indicates that the detection of these strains and the control of nosocomial infections must be strengthened.
Systematic Review and Meta-Analysis of the Epidemiology of Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Isolates
Shanshan Zhang, 1 Xiaoxi Sun, 2 Wenjiao Chang, 2 Yuanyuan Dai, 2 and Xiaoling Ma 2 ,* Herminia de Lencastre, Editor