Susceptibility Loci for Type 2 Diabetes in the Ethnically Endogamous Indian Sindhi Population: A Pooled Blood Genome-Wide Association Study
Type 2 diabetes (T2D) is a complex metabolic derangement that has a strong genetic basis. There is substantial population-specificity in the association of genetic variants with T2D. The Indian urban Sindhi population is at a high risk of T2D. The genetic basis of T2D in this population is unknown....
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Veröffentlicht in: | Genes 2022-07, Vol.13 (8), p.1298 |
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description | Type 2 diabetes (T2D) is a complex metabolic derangement that has a strong genetic basis. There is substantial population-specificity in the association of genetic variants with T2D. The Indian urban Sindhi population is at a high risk of T2D. The genetic basis of T2D in this population is unknown. We interrogated 28 pooled whole blood genomes of 1402 participants from the Diabetes In Sindhi Families In Nagpur (DISFIN) study using Illumina's Global Screening Array. From a total of 608,550 biallelic variants, 140 were significantly associated with T2D after adjusting for comorbidities, batch effects, pooling error, kinship status and pooling variation in a random effects multivariable logistic regression framework. Of the 102 well-characterized genes that these variants mapped onto, 70 genes have been previously reported to be associated with T2D to varying degrees with known functional relevance. Excluding open reading frames, intergenic non-coding elements and pseudogenes, our study identified 22 novel candidate genes in the Sindhi population studied. Our study thus points to the potential, interesting candidate genes associated with T2D in an ethnically endogamous population. These candidate genes need to be fully investigated in future studies. |
doi_str_mv | 10.3390/genes13081298 |
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There is substantial population-specificity in the association of genetic variants with T2D. The Indian urban Sindhi population is at a high risk of T2D. The genetic basis of T2D in this population is unknown. We interrogated 28 pooled whole blood genomes of 1402 participants from the Diabetes In Sindhi Families In Nagpur (DISFIN) study using Illumina's Global Screening Array. From a total of 608,550 biallelic variants, 140 were significantly associated with T2D after adjusting for comorbidities, batch effects, pooling error, kinship status and pooling variation in a random effects multivariable logistic regression framework. Of the 102 well-characterized genes that these variants mapped onto, 70 genes have been previously reported to be associated with T2D to varying degrees with known functional relevance. Excluding open reading frames, intergenic non-coding elements and pseudogenes, our study identified 22 novel candidate genes in the Sindhi population studied. Our study thus points to the potential, interesting candidate genes associated with T2D in an ethnically endogamous population. These candidate genes need to be fully investigated in future studies.</description><identifier>ISSN: 2073-4425</identifier><identifier>EISSN: 2073-4425</identifier><identifier>DOI: 10.3390/genes13081298</identifier><identifier>PMID: 35893037</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Analysis ; Blood pressure ; Case-Control Studies ; Comorbidity ; Diabetes ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - epidemiology ; Disease susceptibility ; Enrollments ; Genes ; Genetic aspects ; Genetic diversity ; Genetic Predisposition to Disease ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Humans ; Hypertension ; Laboratories ; Metabolism ; Methods ; Obesity ; Open reading frames ; Polymorphism, Single Nucleotide ; Population ; Population studies ; Pseudogenes ; Questioning ; Self report ; Type 2 diabetes</subject><ispartof>Genes, 2022-07, Vol.13 (8), p.1298</ispartof><rights>COPYRIGHT 2022 MDPI AG</rights><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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These candidate genes need to be fully investigated in future studies.</description><subject>Analysis</subject><subject>Blood pressure</subject><subject>Case-Control Studies</subject><subject>Comorbidity</subject><subject>Diabetes</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetes Mellitus, Type 2 - epidemiology</subject><subject>Disease susceptibility</subject><subject>Enrollments</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic diversity</subject><subject>Genetic Predisposition to Disease</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Laboratories</subject><subject>Metabolism</subject><subject>Methods</subject><subject>Obesity</subject><subject>Open reading frames</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Population</subject><subject>Population studies</subject><subject>Pseudogenes</subject><subject>Questioning</subject><subject>Self report</subject><subject>Type 2 diabetes</subject><issn>2073-4425</issn><issn>2073-4425</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNptkl1rFDEUhgdRbKm99FYC3ngzbb7mI14I27q2hQWFrXgZssmZ3ZRMMk4ywvwG_7RZW2tXTC5ykjznfTmHUxSvCT5jTODzLXiIhOGWUNE-K44pbljJOa2eP4mPitMY73BeHFOMq5fFEatawTBrjouf6ylqGJLdWGfTjFZBW9SFEd3OAyCKPlq1gQQRWY_SDtAy7bzVyrkZLb0JW9WHKaIbb6zyaG292Vn0JQyTU8kG_x4t8i04MOjChWDQFfjQQ_nNGkCLGLPZbw6t02TmV8WLTrkIpw_nSfH10_L28rpcfb66uVysSs0JTaUATnitO0I63DYaCKtopyqNRdsYBZRUVdvyTaYANznSTBtVY2NoU2tec3ZSfLjXHaZND0aDT6Nychhtr8ZZBmXl4Y-3O7kNP6RgjAi8F3j3IDCG7xPEJHubu-ic8pDbIWktKioY5U1G3_6D3oVp9Lk8SRtcE1ELUf2ltsqBtL4L2VfvReWioZw3FNO97dl_qLwN9FYHD53N7wcJ5X2CHkOMI3SPNRIs9wMkDwYo82-eNuaR_jMu7BfqXsDs</recordid><startdate>20220722</startdate><enddate>20220722</enddate><creator>Pipal, Kanchan V</creator><creator>Mamtani, Manju</creator><creator>Patel, Ashwini A</creator><creator>Jaiswal, Sujeet G</creator><creator>Jaisinghani, Manisha T</creator><creator>Kulkarni, Hemant</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20220722</creationdate><title>Susceptibility Loci for Type 2 Diabetes in the Ethnically Endogamous Indian Sindhi Population: A Pooled Blood Genome-Wide Association Study</title><author>Pipal, Kanchan V ; 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There is substantial population-specificity in the association of genetic variants with T2D. The Indian urban Sindhi population is at a high risk of T2D. The genetic basis of T2D in this population is unknown. We interrogated 28 pooled whole blood genomes of 1402 participants from the Diabetes In Sindhi Families In Nagpur (DISFIN) study using Illumina's Global Screening Array. From a total of 608,550 biallelic variants, 140 were significantly associated with T2D after adjusting for comorbidities, batch effects, pooling error, kinship status and pooling variation in a random effects multivariable logistic regression framework. Of the 102 well-characterized genes that these variants mapped onto, 70 genes have been previously reported to be associated with T2D to varying degrees with known functional relevance. Excluding open reading frames, intergenic non-coding elements and pseudogenes, our study identified 22 novel candidate genes in the Sindhi population studied. Our study thus points to the potential, interesting candidate genes associated with T2D in an ethnically endogamous population. These candidate genes need to be fully investigated in future studies.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>35893037</pmid><doi>10.3390/genes13081298</doi><oa>free_for_read</oa></addata></record> |
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subjects | Analysis Blood pressure Case-Control Studies Comorbidity Diabetes Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - epidemiology Disease susceptibility Enrollments Genes Genetic aspects Genetic diversity Genetic Predisposition to Disease Genome-wide association studies Genome-Wide Association Study Genomes Humans Hypertension Laboratories Metabolism Methods Obesity Open reading frames Polymorphism, Single Nucleotide Population Population studies Pseudogenes Questioning Self report Type 2 diabetes |
title | Susceptibility Loci for Type 2 Diabetes in the Ethnically Endogamous Indian Sindhi Population: A Pooled Blood Genome-Wide Association Study |
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