Replication of genome-wide association signals in Asian Indians with early-onset type 2 diabetes
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To evaluate the association of 87 genetic variants previously associated with type 2 diabetes mellitus (T2DM) in genome-wide association studies of populations of European ancestry in an Asian Indian population with early-onset type 2 diabetes mellitus (EOT2DM).
The study groups comprised of 877 type 2 diabetes individuals, 436 individuals with EOT2DM (age at diagnosis below 35 years), 441 individuals with older T2DM (diagnosis at 35 years or greater) and controls with normal glucose tolerance (NGT) (n = 400 younger than 35 years; n = 438 older than 35 years). The participants were genotyped for 87 SNPs from 44 genes and 27 intergenic loci. Associations were tested using logistic regression.
All the variants in TCF7L2 and CDKN2A/2B showed study-wide significance (p < 1.4 × 10−4) with T2DM, but only rs7903146, rs12243326, rs12255372 of TCF7L2 and rs7020996 of CDKN2A/2B showed study-wide significance (p < 1.4 × 10−4) with EOT2DM in this population. In addition, an intergenic SNP on chromosome 1 (rs10493685) was also shown to be study-wide significant (p = 7.1 × 10−6). Several additional SNPs previously associated with T2DM reached borderline significance in this study, but may have been limited by relatively low sample numbers. Various other SNPs of T2DM were not associated with EOT2DM.
Some of the variants in TCF7L2 and CDKN2A/2B associated with T2DM are associated with EOT2DM as well. An intergenic SNP on chromosome 1p31 showed association only with early-onset T2DM in this Asian Indian population. The lack of association with many other SNPs of T2DM may be a reflection of the lack of power of the study, sample size, differences in the frequencies of genetic polymorphisms in different ethnic groups, effect sizes, as well as ancestral differences in pattern of LD between the genetic variants involved in early- and late-onset T2DM.
KeywordsEarly onset T2D GWAS replication Asian Indian population
This study was supported by the Department of Science and Technology (DST), Government of India, through the project “Replication of Novel Type 2 Diabetes genes in Early-onset type 2 diabetes” awarded to RV.
Compliance with ethical standards
Conflict of interest
The authors declare that there is no duality of interest associated with this manuscript.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Human and animal rights
This article does not contain any studies with animals performed by any of the authors.
Informed consent disclosure
Informed consent was obtained from all patients for being included in the study.
- 1.International Diabetes Federation (2015) IDF diabetes Atlas, 7th edn. International Diabetes Federation, BrusselsGoogle Scholar
- 2.Anjana RM, Pradeepa R, Deepa M, Datta M, Sudha V et al (2011) ICMR–INDIAB Collaborative Study Group. Prevalence of diabetes and prediabetes (impaired fasting glucose and/or impaired glucose tolerance) in urban and rural India: phase I results of the Indian Council of Medical Research-INdiaDIABetes (ICMR-INDIAB) study. Diabetologia 54(12):3022–3027CrossRefPubMedGoogle Scholar
- 14.Anuradha S, Radha V, Deepa R et al (2005) A prevalent amino acid polymorphism at codon 98 (Ala98Val) of the hepatocyte nuclear factor-1alpha is associated with maturity-onset diabetes of the young and younger age at onset of type 2 diabetes in Asian Indians. Diabetes Care 28(10):2430–2435CrossRefPubMedGoogle Scholar
- 31.Deepa M, Pradeepa R, Rema M et al (2003) The Chennai Urban Rural Epidemiology Study (CURES)—study design and methodology (urban component) (CURES-I). J Assoc Phys India 51:863–870Google Scholar
- 32.World Health Organization definition (1999) Diagnosis and classification of diabetes mellitus and its complications: report of a WHO consultation. Part 1: diagnosis and classification of diabetes mellitus. World Health Org., GenevaGoogle Scholar
- 38.Shu XO, Long J, Cai Q, Qi L, Xiang YB (2010) Identification of new genetic risk variants for type 2 diabetes. PLoS Genet 16(9):6Google Scholar
- 57.Grarup N, Andersen G, Krarup NT, Albrechtsen A, Schmitz O et al (2008) Association testing of novel type 2 diabetes risk alleles in the JAZF1, CDC123/CAMK1D, TSPAN8, THADA, ADAMTS9, and NOTCH2 loci with insulin release, insulin sensitivity, and obesity in a population-based sample of 4516 glucose-tolerant middle-aged Danes. Diabetes 57(9):2534–2540CrossRefPubMedPubMedCentralGoogle Scholar