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04.08.2016 | Original Article

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

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

Erschienen in: Acta Diabetologica | Ausgabe 6/2016

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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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Titel: Replication of genome-wide association signals in Asian Indians with early-onset type 2 diabetes
verfasst von: Manickam Chidambaram
Samuel Liju
Banshi Saboo
Kumpatla Sathyavani
Vijay Viswanathan
Nathan Pankratz
Myron Gross
Viswanathan Mohan
Venkatesan Radha
Publikationsdatum: 04.08.2016
Verlag: Springer Milan
Erschienen in: Acta Diabetologica / Ausgabe 6/2016
Print ISSN: 0940-5429
Elektronische ISSN: 1432-5233
DOI: https://doi.org/10.1007/s00592-016-0889-2

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

Abstract

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