Genetic associations of TMEM154, PRC1 and ZFAND6 loci with type 2 diabetes in an endogamous business community of North India.
<h4>Background</h4>More than 250 loci have been identified by genome-wide scans for type 2 diabetes in different populations. South Asians have a very different manifestation of the diseases and hence role of these loci need to be investigated among Indians with huge burden of cardio-met...
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| 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.0291339 |
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| author | Gagandeep Kaur Walia Pratiksha Sharma Tripti Agarwal Moti Lal Himanshu Negandhi Dorairaj Prabhakaran Rajesh Khadgawat Mohinder Pal Sachdeva Vipin Gupta |
| author_facet | Gagandeep Kaur Walia Pratiksha Sharma Tripti Agarwal Moti Lal Himanshu Negandhi Dorairaj Prabhakaran Rajesh Khadgawat Mohinder Pal Sachdeva Vipin Gupta |
| author_sort | Gagandeep Kaur Walia |
| collection | DOAJ |
| description | <h4>Background</h4>More than 250 loci have been identified by genome-wide scans for type 2 diabetes in different populations. South Asians have a very different manifestation of the diseases and hence role of these loci need to be investigated among Indians with huge burden of cardio-metabolic disorders. Thus the present study aims to validate the recently identified GWAS loci in an endogamous caste population in North India.<h4>Methods</h4>219 T2D cases and 184 controls were recruited from hospitals and genotyped for 15 GWAS loci of T2D. Regression models adjusted for covariates were run to examine the association for T2D and fasting glucose levels.<h4>Results</h4>We validated three variants for T2D namely, rs11634397 at ZFAND6 (OR = 3.05, 95%CI = 1.02-9.19, p = 0.047) and rs8042680 at PRC1 (OR = 3.67, 95%CI = 1.13-11.93, p = 0.031) showing higher risk and rs6813195 at TMEM154 (OR = 0.28, 95%CI = 0.09-0.90, p = 0.033) showing protective effect. The combined risk of 9 directionally consistent variants was also found to be significantly associated with T2D (OR = 1.91, 95%CI = 1.18-3.08, p = 0.008). One variant rs10842994 at KLHDC5 was validated for 9.15mg/dl decreased fasting glucose levels (SE = -17.25-1.05, p = 0.027).<h4>Conclusion</h4>We confirm the role of ZFAND6, PRC1 and TMEM154 in the pathophysiology of type 2 diabetes among Indians. More efforts are needed with larger sample sizes to validate the diabetes GWAS loci in South Asian populations for wider applicability. |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-11T21:21:57Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj.art-6db98e202e8441b7825e2bf780a3e4db2023-09-28T05:31:15ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01189e029133910.1371/journal.pone.0291339Genetic associations of TMEM154, PRC1 and ZFAND6 loci with type 2 diabetes in an endogamous business community of North India.Gagandeep Kaur WaliaPratiksha SharmaTripti AgarwalMoti LalHimanshu NegandhiDorairaj PrabhakaranRajesh KhadgawatMohinder Pal SachdevaVipin Gupta<h4>Background</h4>More than 250 loci have been identified by genome-wide scans for type 2 diabetes in different populations. South Asians have a very different manifestation of the diseases and hence role of these loci need to be investigated among Indians with huge burden of cardio-metabolic disorders. Thus the present study aims to validate the recently identified GWAS loci in an endogamous caste population in North India.<h4>Methods</h4>219 T2D cases and 184 controls were recruited from hospitals and genotyped for 15 GWAS loci of T2D. Regression models adjusted for covariates were run to examine the association for T2D and fasting glucose levels.<h4>Results</h4>We validated three variants for T2D namely, rs11634397 at ZFAND6 (OR = 3.05, 95%CI = 1.02-9.19, p = 0.047) and rs8042680 at PRC1 (OR = 3.67, 95%CI = 1.13-11.93, p = 0.031) showing higher risk and rs6813195 at TMEM154 (OR = 0.28, 95%CI = 0.09-0.90, p = 0.033) showing protective effect. The combined risk of 9 directionally consistent variants was also found to be significantly associated with T2D (OR = 1.91, 95%CI = 1.18-3.08, p = 0.008). One variant rs10842994 at KLHDC5 was validated for 9.15mg/dl decreased fasting glucose levels (SE = -17.25-1.05, p = 0.027).<h4>Conclusion</h4>We confirm the role of ZFAND6, PRC1 and TMEM154 in the pathophysiology of type 2 diabetes among Indians. More efforts are needed with larger sample sizes to validate the diabetes GWAS loci in South Asian populations for wider applicability.https://doi.org/10.1371/journal.pone.0291339 |
| spellingShingle | Gagandeep Kaur Walia Pratiksha Sharma Tripti Agarwal Moti Lal Himanshu Negandhi Dorairaj Prabhakaran Rajesh Khadgawat Mohinder Pal Sachdeva Vipin Gupta Genetic associations of TMEM154, PRC1 and ZFAND6 loci with type 2 diabetes in an endogamous business community of North India. PLoS ONE |
| title | Genetic associations of TMEM154, PRC1 and ZFAND6 loci with type 2 diabetes in an endogamous business community of North India. |
| title_full | Genetic associations of TMEM154, PRC1 and ZFAND6 loci with type 2 diabetes in an endogamous business community of North India. |
| title_fullStr | Genetic associations of TMEM154, PRC1 and ZFAND6 loci with type 2 diabetes in an endogamous business community of North India. |
| title_full_unstemmed | Genetic associations of TMEM154, PRC1 and ZFAND6 loci with type 2 diabetes in an endogamous business community of North India. |
| title_short | Genetic associations of TMEM154, PRC1 and ZFAND6 loci with type 2 diabetes in an endogamous business community of North India. |
| title_sort | genetic associations of tmem154 prc1 and zfand6 loci with type 2 diabetes in an endogamous business community of north india |
| url | https://doi.org/10.1371/journal.pone.0291339 |
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