Replication and Relevance of Multiple Susceptibility Loci Discovered from Genome Wide Association Studies for Type 2 Diabetes in an Indian Population
| العنوان: | Replication and Relevance of Multiple Susceptibility Loci Discovered from Genome Wide Association Studies for Type 2 Diabetes in an Indian Population |
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| المؤلفون: | Prabha Adhikari, Kapaettu Satyamoorthy, Sydney C. D’Souza, Nagaraja M. Phani, Shivashankara K. Nagri, Padmalatha S. Rai |
| المصدر: | PLoS ONE PLoS ONE, Vol 11, Iss 6, p e0157364 (2016) |
| بيانات النشر: | Public Library of Science, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Heredity, Multifactor Dimensionality Reduction, endocrine system diseases, Epidemiology, lcsh:Medicine, Gene Expression, Genome-wide association study, Biochemistry, Body Mass Index, 0302 clinical medicine, Medicine and Health Sciences, lcsh:Science, Cation Transport Proteins, 2. Zero hunger, Genetics, education.field_of_study, Multidisciplinary, SLC30A8, biology, RNA-Binding Proteins, Genomics, Middle Aged, Lipids, Genetic Mapping, Cholesterol, Female, Transcription Factor 7-Like 2 Protein, Research Article, Adult, Risk, Population, India, 030209 endocrinology & metabolism, Single-nucleotide polymorphism, Variant Genotypes, Zinc Transporter 8, Genetic Predisposition, Polymorphism, Single Nucleotide, Ethnic Epidemiology, 03 medical and health sciences, Genome-Wide Association Studies, Cyclin-Dependent Kinase Inhibitor p18, Humans, Genetic Predisposition to Disease, education, Alleles, Cyclin-Dependent Kinase Inhibitor p16, Aged, Homeodomain Proteins, Evolutionary Biology, Multifactor dimensionality reduction, Population Biology, Genome, Human, lcsh:R, Case-control study, nutritional and metabolic diseases, Biology and Life Sciences, Computational Biology, Human Genetics, Epistasis, Genetic, Odds ratio, Genome Analysis, 030104 developmental biology, Logistic Models, Diabetes Mellitus, Type 2, ROC Curve, Genetic Loci, Case-Control Studies, Genetics of Disease, biology.protein, lcsh:Q, TCF7L2, Population Genetics, Genome-Wide Association Study, Transcription Factors |
| الوصف: | 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 nonsignificant variants may interact with one another resulting in increased disease susceptibility in the population tested. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5d7fe7216c607990a21720304a27bb8eTest http://europepmc.org/articles/PMC4911058Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5d7fe7216c607990a21720304a27bb8e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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