Decoding type 2 diabetes mellitus genetic risk variants in Pakistani Pashtun ethnic population using the nascent whole exome sequencing and MassARRAY genotyping: A case-control association study.
Genome-wide association studies have greatly increased the number of T2DM associated risk variants but most of them have focused on populations of European origin. There is scarcity of such studies in developing countries including Pakistan. High prevalence of T2DM in Pakistani population prompted u...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0281070 |
| _version_ | 1797774472694988800 |
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| author | Asif Jan Zakiullah Sajid Ali Basir Muhammad Amina Arshad Yasar Shah Haji Bahadur Hamayun Khan Fazli Khuda Rani Akbar Kiran Ijaz |
| author_facet | Asif Jan Zakiullah Sajid Ali Basir Muhammad Amina Arshad Yasar Shah Haji Bahadur Hamayun Khan Fazli Khuda Rani Akbar Kiran Ijaz |
| author_sort | Asif Jan |
| collection | DOAJ |
| description | Genome-wide association studies have greatly increased the number of T2DM associated risk variants but most of them have focused on populations of European origin. There is scarcity of such studies in developing countries including Pakistan. High prevalence of T2DM in Pakistani population prompted us to design this study. We have devised a two stage (the discovery stage and validation stage) case-control study in Pashtun ethnic population in which 500 T2DM cases and controls each have been recruited to investigate T2DM genetic risk variants. In discovery stage Whole Exome Sequencing (WES) was used to identify and suggest T2DM pathogenic SNPs, based on SIFT and Polyphen scores; whereas in validation stage the selected variants were confirmed for T2DM association using MassARRAY genotyping and appropriate statistical tests. Results of the study showed the target positive association of rs1801282/PPARG (OR = 1.24, 95%Cl = 1.20-1.46, P = 0.010), rs745975/HNF4A (OR = 1.30, 95%Cl = 1.06-1.38, P = 0.004), rs806052/GLIS3 (OR = 1.32, 95%Cl = 1.07-1.66, P = 0.016), rs8192552/MTNR1B (OR = 1.53, 95%Cl = 0.56-1.95, P = 0.012) and rs1805097/IRS-2 (OR = 1.27, 95%Cl = 1.36-1.92, P = 0.045), with T2DM; whereas rs6415788/GLIS3, rs61788900/NOTCH2, rs61788901/NOTCH2 and rs11810554/NOTCH2 (P>0.05) showed no significant association. Identification of genetic risk factors/variants can be used in defining high risk subjects assessment, and disease prevention. |
| first_indexed | 2024-03-12T22:21:36Z |
| format | Article |
| id | doaj.art-42cd9d1a295947f7b9f7ef79a1c2bd57 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-12T22:21:36Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-42cd9d1a295947f7b9f7ef79a1c2bd572023-07-23T05:31:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01181e028107010.1371/journal.pone.0281070Decoding type 2 diabetes mellitus genetic risk variants in Pakistani Pashtun ethnic population using the nascent whole exome sequencing and MassARRAY genotyping: A case-control association study.Asif JanZakiullahSajid AliBasir MuhammadAmina ArshadYasar ShahHaji BahadurHamayun KhanFazli KhudaRani AkbarKiran IjazGenome-wide association studies have greatly increased the number of T2DM associated risk variants but most of them have focused on populations of European origin. There is scarcity of such studies in developing countries including Pakistan. High prevalence of T2DM in Pakistani population prompted us to design this study. We have devised a two stage (the discovery stage and validation stage) case-control study in Pashtun ethnic population in which 500 T2DM cases and controls each have been recruited to investigate T2DM genetic risk variants. In discovery stage Whole Exome Sequencing (WES) was used to identify and suggest T2DM pathogenic SNPs, based on SIFT and Polyphen scores; whereas in validation stage the selected variants were confirmed for T2DM association using MassARRAY genotyping and appropriate statistical tests. Results of the study showed the target positive association of rs1801282/PPARG (OR = 1.24, 95%Cl = 1.20-1.46, P = 0.010), rs745975/HNF4A (OR = 1.30, 95%Cl = 1.06-1.38, P = 0.004), rs806052/GLIS3 (OR = 1.32, 95%Cl = 1.07-1.66, P = 0.016), rs8192552/MTNR1B (OR = 1.53, 95%Cl = 0.56-1.95, P = 0.012) and rs1805097/IRS-2 (OR = 1.27, 95%Cl = 1.36-1.92, P = 0.045), with T2DM; whereas rs6415788/GLIS3, rs61788900/NOTCH2, rs61788901/NOTCH2 and rs11810554/NOTCH2 (P>0.05) showed no significant association. Identification of genetic risk factors/variants can be used in defining high risk subjects assessment, and disease prevention.https://doi.org/10.1371/journal.pone.0281070 |
| spellingShingle | Asif Jan Zakiullah Sajid Ali Basir Muhammad Amina Arshad Yasar Shah Haji Bahadur Hamayun Khan Fazli Khuda Rani Akbar Kiran Ijaz Decoding type 2 diabetes mellitus genetic risk variants in Pakistani Pashtun ethnic population using the nascent whole exome sequencing and MassARRAY genotyping: A case-control association study. PLoS ONE |
| title | Decoding type 2 diabetes mellitus genetic risk variants in Pakistani Pashtun ethnic population using the nascent whole exome sequencing and MassARRAY genotyping: A case-control association study. |
| title_full | Decoding type 2 diabetes mellitus genetic risk variants in Pakistani Pashtun ethnic population using the nascent whole exome sequencing and MassARRAY genotyping: A case-control association study. |
| title_fullStr | Decoding type 2 diabetes mellitus genetic risk variants in Pakistani Pashtun ethnic population using the nascent whole exome sequencing and MassARRAY genotyping: A case-control association study. |
| title_full_unstemmed | Decoding type 2 diabetes mellitus genetic risk variants in Pakistani Pashtun ethnic population using the nascent whole exome sequencing and MassARRAY genotyping: A case-control association study. |
| title_short | Decoding type 2 diabetes mellitus genetic risk variants in Pakistani Pashtun ethnic population using the nascent whole exome sequencing and MassARRAY genotyping: A case-control association study. |
| title_sort | decoding type 2 diabetes mellitus genetic risk variants in pakistani pashtun ethnic population using the nascent whole exome sequencing and massarray genotyping a case control association study |
| url | https://doi.org/10.1371/journal.pone.0281070 |
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