Dataset Information

Risk Alleles in/near ADCY5, ADRA2A, CDKAL1, CDKN2A/B, GRB10, and TCF7L2 Elevate Plasma Glucose Levels at Birth and in Early Childhood: Results from the FAMILY Study.

ABSTRACT: BACKGROUND:Metabolic abnormalities that lead to type 2 diabetes mellitus begin in early childhood. OBJECTIVES:We investigate whether common genetic variants identified in adults have an effect on glucose in early life. METHODS:610 newborns, 463 mothers, and 366 fathers were included in the present study. Plasma glucose and anthropometric characteristics were collected at birth, 3, and 5 years. After quality assessment, 37 SNPs, which have demonstrated an association with fasting plasma glucose at the genome-wide threshold in adults, were studied. Quantitative trait disequilibrium tests and mixed-effects regressions were conducted to estimate an effect of the SNPs on glucose. RESULTS:Risk alleles for 6 loci increased glucose levels from birth to 5 years of age (ADCY5, ADRA2A, CDKAL1, CDKN2A/B, GRB10, and TCF7L2, 4.85x10-3 ? P ? 4.60x10-2). Together, these 6 SNPs increase glucose by 0.05 mmol/L for each risk allele in a genotype score (P = 6.33x10-5). None of the associations described in the present study have been reported previously in early childhood. CONCLUSION:Our data support the notion that a subset of loci contributing to plasma glucose variation in adults has an effect at birth and in early life.

SUBMITTER: Sohani ZN

PROVIDER: S-EPMC4822946 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Risk Alleles in/near ADCY5, ADRA2A, CDKAL1, CDKN2A/B, GRB10, and TCF7L2 Elevate Plasma Glucose Levels at Birth and in Early Childhood: Results from the FAMILY Study.

Sohani Zahra N ZN Anand Sonia S SS Robiou-du-Pont Sebastien S Morrison Katherine M KM McDonald Sarah D SD Atkinson Stephanie A SA Teo Koon K KK Meyre David D

PloS one 20160406 4

<h4>Background</h4>Metabolic abnormalities that lead to type 2 diabetes mellitus begin in early childhood.<h4>Objectives</h4>We investigate whether common genetic variants identified in adults have an effect on glucose in early life.<h4>Methods</h4>610 newborns, 463 mothers, and 366 fathers were included in the present study. Plasma glucose and anthropometric characteristics were collected at birth, 3, and 5 years. After quality assessment, 37 SNPs, which have demonstrated an association with fa ...[more]

PMID: 27049325

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Project description:BackgroundSeveral type 2 diabetes (T2D) susceptibility loci identified via genome-wide association studies were found to be replicated among various populations. However, the influence of these loci on T2D in Thai population is unknown. The aim of this study was to investigate the influence of eight single nucleotide polymorphisms (SNPs) reported in GWA studies on T2D and related quantitative traits in Thai population.MethodsEight SNPs in or near the KCNQ1, CDKN2A/2B, SLC30A8, HHEX, CDKAL1, TCF7L2, MTNR1B, and UBE2E2 genes were genotyped. A case-control association study comprising 500 Thai patients with T2D and 500 ethnically-matched control subjects was conducted. Associations between SNPs and T2D were examined by logistic regression analysis. The impact of these SNPs on quantitative traits was examined by linear regression among case and control subjects.ResultsFive SNPs in KCNQ1 (rs2237892), CDK2A/2B (rs108116610, SLC30A8 (rs13266634), TCF7L2 (rs7903146) and MTNR1B (rs1387153) were found to be marginally associated with risk of developing T2D, with odds ratios ranging from 1.43 to 2.02 (p = 0.047 to 3.0 × 10-4) with adjustments for age, sex, and body mass index. Interestingly, SNP rs13266634 of SLC30A8 gene reached statistical significance after correcting for multiple testing (p = 0.0003) (p < 0.006 after Bonferroni correction). However, no significant association was detected between HHEX (rs1111875), CDKAL1 (rs7756992), or UBE2E2 (rs7612463) and T2D. We also observed association between rs10811661 and both waist circumference and waist-hip ratio (p = 0.007 and p = 0.023, respectively). In addition, rs13266634 in SLC30A8 was associated with glycated hemoglobin (p = 0.018), and rs7903146 in TCF7L2 was associated with high-density lipoprotein cholesterol level (p = 0.023).ConclusionOf the eight genes included in our analysis, significant association was observed between KCNQ1, CDKN2A/2B, SLC30A8, TCF7L2, and MTNR1B loci and T2D in our Thai study population. Of these, CDKN2A/2B, SLC30A8, and TCF7L2 genes were also significantly associated with anthropometric, glycemic and lipid characteristics. Larger cohort studies and meta-analyses are needed to further confirm the effect of these variants in Thai population.

Dataset Information

Risk Alleles in/near ADCY5, ADRA2A, CDKAL1, CDKN2A/B, GRB10, and TCF7L2 Elevate Plasma Glucose Levels at Birth and in Early Childhood: Results from the FAMILY Study.

Publications

Risk Alleles in/near ADCY5, ADRA2A, CDKAL1, CDKN2A/B, GRB10, and TCF7L2 Elevate Plasma Glucose Levels at Birth and in Early Childhood: Results from the FAMILY Study.

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