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Acta Diabetologica

, Volume 53, Issue 6, pp 915–923 | Cite as

Replication of genome-wide association signals in Asian Indians with early-onset type 2 diabetes

  • Manickam Chidambaram
  • Samuel Liju
  • Banshi Saboo
  • Kumpatla Sathyavani
  • Vijay Viswanathan
  • Nathan Pankratz
  • Myron Gross
  • Viswanathan Mohan
  • Venkatesan RadhaEmail author
Original Article

Abstract

Aims

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).

Methods

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.

Results

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.

Conclusions

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.

Keywords

Early onset T2D GWAS replication Asian Indian population 

Notes

Acknowledgments

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.

Ethical standard

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.

Supplementary material

592_2016_889_MOESM1_ESM.xlsx (90 kb)
Supplementary material 1 (XLSX 91 kb)

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Copyright information

© Springer-Verlag Italia 2016

Authors and Affiliations

  • Manickam Chidambaram
    • 1
    • 2
  • Samuel Liju
    • 1
  • Banshi Saboo
    • 3
  • Kumpatla Sathyavani
    • 4
  • Vijay Viswanathan
    • 4
  • Nathan Pankratz
    • 5
  • Myron Gross
    • 5
  • Viswanathan Mohan
    • 1
    • 6
  • Venkatesan Radha
    • 1
    Email author
  1. 1.Madras Diabetes Research FoundationChennaiIndia
  2. 2.Division of Cardiovascular ResearchSidra Medical and Research CenterDohaQatar
  3. 3.Diabetologist and Endocrine and Metabolic Physician at Diabetes Care and Hormone ClinicAhmedabadIndia
  4. 4.M.V. Hospital for Diabetes and Prof. M. Viswanathan Diabetes Research CentreChennaiIndia
  5. 5.Department of Laboratory Medicine PathologyMedical School University of MinnesotaMinneapolisUSA
  6. 6.Dr. Mohan’s Diabetes Specialities Centre, WHO Collaborating Centre for Non-Communicable Diseases Prevention and ControlIDF Centre of EducationChennaiIndia

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