TY - JOUR
T1 - Replication and Relevance of Multiple Susceptibility Loci Discovered from Genome Wide Association Studies for Type 2 Diabetes in an Indian Population
AU - Phani, Nagaraja M.
AU - Adhikari, Prabha
AU - Nagri, Shivashankara K.
AU - D'Souza, Sydney C.
AU - Satyamoorthy, Kapaettu
AU - Rai, Padmalatha S.
N1 - Funding Information:
We would like to thank Indian Council of Medical Research (ICMR), Technology Information Forecasting and Assessment Council-Centre of Relevance and Excellence (TIFAC-CORE) in Pharmacogenomics at the School of Life Sciences, Government of India, Dr. TMA Pai Endowment Chair in Pharmacogenomics and Public Health Genomics, Manipal University for financial and technical support.
Funding Information:
Funding: The authors would like to thank the Indian Council of Medical Research (ICMR), Technology Information Forecasting and Assessment Council-Centre of Relevance and Excellence (TIFAC-CORE) in Pharmacogenomics at the School of Life Sciences, Government of India, Dr. TMA Pai Endowment Chair in Pharmacogenomics and Public Health Genomics, Manipal University for financial and technical support. The funders had no role in study design, data
Publisher Copyright:
Copyright: © 2016 Phani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016
Y1 - 2016
N2 - AIM: Several genetic variants for type 2 diabetes (T2D) have been identified through genome wide association studies (GWAS) from Caucasian population; however replication studies were not consistent across various ethnicities. Objective of the current study is to examine the possible correlation of 9 most significant GWAS single nucleotide polymorphisms (SNPs) for T2D susceptibility as well as the interactive effect of these variants on the risk of T2D in an Indian population.METHODS: Case-control cohorts of 1156 individuals were genotyped for 9 SNPs from an Indian population. Association analyses were performed using logistic regression after adjusting for covariates. Multifactor dimensionality reduction (MDR) analysis was adopted to determine gene-gene interactions and discriminatory power of combined SNP effect was assessed by grouping individuals based on the number of risk alleles and by calculating area under the receiver-operator characteristic curve (AUC).RESULTS: We confirm the association of TCF7L2 (rs7903146) and SLC30A8 (rs13266634) with T2D. MDR analysis showed statistically significant interactions among four SNPs of SLC30A8 (rs13266634), IGF2BP2 (rs4402960), HHEX (rs1111875) and CDKN2A (rs10811661) genes. Cumulative analysis showed an increase in odds ratio against the baseline group of individuals carrying 5 to 6 risk alleles and discriminatory power of genetic test based on 9 variants showed higher AUC value when analyzed along with body mass index (BMI).CONCLUSION: These results provide a strong evidence for independent association between T2D and SNPs for in TCF7L2 and SLC30A8. MDR analysis demonstrates that independently non-significant variants may interact with one another resulting in increased disease susceptibility in the population tested.
AB - AIM: Several genetic variants for type 2 diabetes (T2D) have been identified through genome wide association studies (GWAS) from Caucasian population; however replication studies were not consistent across various ethnicities. Objective of the current study is to examine the possible correlation of 9 most significant GWAS single nucleotide polymorphisms (SNPs) for T2D susceptibility as well as the interactive effect of these variants on the risk of T2D in an Indian population.METHODS: Case-control cohorts of 1156 individuals were genotyped for 9 SNPs from an Indian population. Association analyses were performed using logistic regression after adjusting for covariates. Multifactor dimensionality reduction (MDR) analysis was adopted to determine gene-gene interactions and discriminatory power of combined SNP effect was assessed by grouping individuals based on the number of risk alleles and by calculating area under the receiver-operator characteristic curve (AUC).RESULTS: We confirm the association of TCF7L2 (rs7903146) and SLC30A8 (rs13266634) with T2D. MDR analysis showed statistically significant interactions among four SNPs of SLC30A8 (rs13266634), IGF2BP2 (rs4402960), HHEX (rs1111875) and CDKN2A (rs10811661) genes. Cumulative analysis showed an increase in odds ratio against the baseline group of individuals carrying 5 to 6 risk alleles and discriminatory power of genetic test based on 9 variants showed higher AUC value when analyzed along with body mass index (BMI).CONCLUSION: These results provide a strong evidence for independent association between T2D and SNPs for in TCF7L2 and SLC30A8. MDR analysis demonstrates that independently non-significant variants may interact with one another resulting in increased disease susceptibility in the population tested.
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U2 - 10.1371/journal.pone.0157364
DO - 10.1371/journal.pone.0157364
M3 - Article
C2 - 27310578
AN - SCOPUS:85009793629
SN - 1932-6203
VL - 11
SP - e0157364
JO - PLoS One
JF - PLoS One
IS - 6
M1 - e0157364
ER -
