1.
Trans-ethnic Meta-analysis and Functional Annotation Illuminates theĀ Genetic Architecture of Fasting Glucose and Insulin.
Liu, CT, Raghavan, S, Maruthur, N, Kabagambe, EK, Hong, J, Ng, MC, Hivert, MF, Lu, Y, An, P, Bentley, AR, et al
American journal of human genetics. 2016;(1):56-75
Abstract
Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loci.
2.
Fasting capillary blood glucose: an appropriate measurement in screening for diabetes and pre-diabetes in low-resource rural settings.
Zhao, X, Zhao, W, Zhang, H, Li, J, Shu, Y, Li, S, Cai, L, Zhou, J, Li, Y, Hu, R
Journal of endocrinological investigation. 2013;(1):33-7
Abstract
OBJECTIVE To evaluate the efficiency of fasting capillary blood glucose (FCG) measurement as compared with fasting venous plasma glucose (FPG) measurement in screening diabetes and pre-diabetes in low-resource rural settings. SUBJECTS AND METHODS In 2010, 993 participants were randomly selected from 9 villages in Yunnan province using cluster sampling method. Samples for FCG and FPG test were obtained after demographics and physical examination. The oral glucose tolerance test was performed in parallel as gold standard for diagnosis. Diagnostic capacities of the FCG measurement in predicting undiagnosed diabetes and pre-diabetes were assessed. The performance of FCG and FPG tests was compared. RESULTS Fifty-seven individuals with undiagnosed diabetes and 145 subjects with pre-diabetes were detected. The concordance between FCG and FPG levels was high (r = 0.75, p < 0.001). The area under the curve (AUC) for FCG test in predicting diabetes was 0.88 [95% confidence interval (CI) 0.82-0.93] with the optimal cutoff value of 5.65 mmol/l, sensitivity of 84.2%, and specificity of 79.3%. The corresponding values in FPG tests were 0.92 (95% CI 0.88-0.97) (AUC), 6.51 mmol/l (optimal cutoff point), 82.5% (sensitivity) and 98.3% (specificity), respectively. No significant difference was found in the AUC for the two screening strategies. CONCLUSION FCG measurement is considered to be a convenient, practicable screening method in low-resource rural communities with acceptable test properties.