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

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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.

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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.

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Author notes

  1. Manickam Chidambaram

    Present address: Division of Cardiovascular Research, Sidra Medical and Research Center, Doha, Qatar

Authors and Affiliations

  1. Madras Diabetes Research Foundation, 4, Conran Smith Road, Gopalapuram, Chennai, 600 086, India

    Manickam Chidambaram, Samuel Liju, Viswanathan Mohan & Venkatesan Radha

  2. Diabetologist and Endocrine and Metabolic Physician at Diabetes Care and Hormone Clinic, Ahmedabad, Gujarat, India

    Banshi Saboo

  3. M.V. Hospital for Diabetes and Prof. M. Viswanathan Diabetes Research Centre, Chennai, Tamil Nadu, India

    Kumpatla Sathyavani & Vijay Viswanathan

  4. Department of Laboratory Medicine Pathology, Medical School University of Minnesota, Minneapolis, MN, USA

    Nathan Pankratz & Myron Gross

  5. Dr. Mohan’s Diabetes Specialities Centre, WHO Collaborating Centre for Non-Communicable Diseases Prevention and Control, IDF Centre of Education, Chennai, India

    Viswanathan Mohan

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  1. Manickam Chidambaram
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  2. Samuel Liju
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Chidambaram, M., Liju, S., Saboo, B. et al. Replication of genome-wide association signals in Asian Indians with early-onset type 2 diabetes. Acta Diabetol 53, 915–923 (2016). https://doi.org/10.1007/s00592-016-0889-2

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