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

Chidambaram Manickam, Samuel Liju, Banshi Saboo, Kumpatla Sathyavani, Vijay Viswanathan, Nathan Pankratz, Myron Gross, Viswanathan Mohan, Venkatesan Radha

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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.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalActa Diabetologica
DOIs
Publication statusAccepted/In press - 4 Aug 2016

Fingerprint

Type 2 Diabetes Mellitus
Genome
Single Nucleotide Polymorphism
Population
Chromosomes, Human, Pair 1
Genome-Wide Association Study
Genetic Polymorphisms
Ethnic Groups
Sample Size
Chromosomes
Logistic Models

Keywords

  • Asian Indian population
  • Early onset T2D
  • GWAS replication

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Manickam, C., Liju, S., Saboo, B., Sathyavani, K., Viswanathan, V., Pankratz, N., ... Radha, V. (Accepted/In press). Replication of genome-wide association signals in Asian Indians with early-onset type 2 diabetes. Acta Diabetologica, 1-9. https://doi.org/10.1007/s00592-016-0889-2

Replication of genome-wide association signals in Asian Indians with early-onset type 2 diabetes. / Manickam, Chidambaram; Liju, Samuel; Saboo, Banshi; Sathyavani, Kumpatla; Viswanathan, Vijay; Pankratz, Nathan; Gross, Myron; Mohan, Viswanathan; Radha, Venkatesan.

In: Acta Diabetologica, 04.08.2016, p. 1-9.

Research output: Contribution to journalArticle

Manickam, C, Liju, S, Saboo, B, Sathyavani, K, Viswanathan, V, Pankratz, N, Gross, M, Mohan, V & Radha, V 2016, 'Replication of genome-wide association signals in Asian Indians with early-onset type 2 diabetes', Acta Diabetologica, pp. 1-9. https://doi.org/10.1007/s00592-016-0889-2
Manickam, Chidambaram ; Liju, Samuel ; Saboo, Banshi ; Sathyavani, Kumpatla ; Viswanathan, Vijay ; Pankratz, Nathan ; Gross, Myron ; Mohan, Viswanathan ; Radha, Venkatesan. / Replication of genome-wide association signals in Asian Indians with early-onset type 2 diabetes. In: Acta Diabetologica. 2016 ; pp. 1-9.
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AU - Viswanathan, Vijay

AU - Pankratz, Nathan

AU - Gross, Myron

AU - Mohan, Viswanathan

AU - Radha, Venkatesan

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N2 - 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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