Genome-Wide Association Study of Metabolic Syndrome Reveals Primary Genetic Variants at <em>CETP</em> Locus in Indians
Indians, a rapidly growing population, constitute vast genetic heterogeneity to that of Western population; however they have become a sedentary population in past decades due to rapid urbanization ensuing in the amplified prevalence of metabolic syndrome (MetS). We performed a genome-wide associati...
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MDPI AG
2019-07-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/9/8/321 |
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| author | Gauri Prasad Khushdeep Bandesh Anil K. Giri Yasmeen Kauser Prakriti Chanda Vaisak Parekatt INDICO Sandeep Mathur Sri Venkata Madhu Pradeep Venkatesh Anil Bhansali Raman K. Marwaha Analabha Basu Nikhil Tandon Dwaipayan Bharadwaj |
| author_facet | Gauri Prasad Khushdeep Bandesh Anil K. Giri Yasmeen Kauser Prakriti Chanda Vaisak Parekatt INDICO Sandeep Mathur Sri Venkata Madhu Pradeep Venkatesh Anil Bhansali Raman K. Marwaha Analabha Basu Nikhil Tandon Dwaipayan Bharadwaj |
| author_sort | Gauri Prasad |
| collection | DOAJ |
| description | Indians, a rapidly growing population, constitute vast genetic heterogeneity to that of Western population; however they have become a sedentary population in past decades due to rapid urbanization ensuing in the amplified prevalence of metabolic syndrome (MetS). We performed a genome-wide association study (GWAS) of MetS in 10,093 Indian individuals (6617 MetS and 3476 controls) of Indo-European origin, that belong to our previous biorepository of The Indian Diabetes Consortium (INDICO). The study was conducted in two stages—discovery phase (<i>N</i> = 2158) and replication phase (<i>N</i> = 7935). We discovered two variants within/near the <i>CETP</i> gene—rs1800775 and rs3816117—associated with MetS at genome-wide significance level during replication phase in Indians. Additional <i>CETP</i> loci rs7205804, rs1532624, rs3764261, rs247617, and rs173539 also cropped up as modest signals in Indians. Haplotype association analysis revealed GCCCAGC as the strongest haplotype within the <i>CETP</i> locus constituting all seven <i>CETP</i> signals. In combined analysis, we perceived a novel and functionally relevant sub-GWAS significant locus—rs16890462 in the vicinity of <i>SFRP1</i> gene. Overlaying gene regulatory data from ENCODE database revealed that single nucleotide polymorphism (SNP) rs16890462 resides in repressive chromatin in human subcutaneous adipose tissue as characterized by the enrichment of H3K27me3 and CTCF marks (repressive gene marks) and diminished H3K36me3 marks (activation gene marks). The variant displayed active DNA methylation marks in adipose tissue, suggesting its likely regulatory activity. Further, the variant also disrupts a potential binding site of a key transcription factor, NRF2, which is known for involvement in obesity and metabolic syndrome. |
| first_indexed | 2024-04-13T01:19:40Z |
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| id | doaj.art-2fe1974220a349b4a5b0b20c0bf888a6 |
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| language | English |
| last_indexed | 2024-04-13T01:19:40Z |
| publishDate | 2019-07-01 |
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| series | Biomolecules |
| spelling | doaj.art-2fe1974220a349b4a5b0b20c0bf888a62022-12-22T03:08:47ZengMDPI AGBiomolecules2218-273X2019-07-019832110.3390/biom9080321biom9080321Genome-Wide Association Study of Metabolic Syndrome Reveals Primary Genetic Variants at <em>CETP</em> Locus in IndiansGauri Prasad0Khushdeep Bandesh1Anil K. Giri2Yasmeen Kauser3Prakriti Chanda4Vaisak Parekatt5INDICO6Sandeep Mathur7Sri Venkata Madhu8Pradeep Venkatesh9Anil Bhansali10Raman K. Marwaha11Analabha Basu12Nikhil Tandon13Dwaipayan Bharadwaj14Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, New Delhi 110025, IndiaGenomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, New Delhi 110025, IndiaGenomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, New Delhi 110025, IndiaGenomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, New Delhi 110025, IndiaSystems Genomics Laboratory, School of Biotechnology, Jawaharlal Nehru University, New Delhi 110067, IndiaGenomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, New Delhi 110025, IndiaMembership of INDICO consortium has been listed in back matter.Department of Endocrinology, S.M.S. Medical College, Jaipur, Rajasthan 302004, IndiaDepartment of Endocrinology, Centre for Diabetes Endocrinology & Metabolism, University College of Medical Sciences (University of Delhi) & GTB Hospital, New Delhi 110095, IndiaDr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi 110029, IndiaDepartment of Endocrinology, Post Graduate Institute of Medical Education and Research, Sector-12, Chandigarh 160012, IndiaDepartment of Endocrinology, International Life Sciences Institute, New Delhi 110024, IndiaNational Institute of Biomedical Genomics, P.O.: Netaji Subhas Sanatorium, Kalyani 741251, West Bengal, IndiaDepartment of Endocrinology, All India Institute of Medical Sciences, New Delhi 110029, IndiaAcademy of Scientific and Innovative Research, CSIR-Institute of Genomics and Integrative Biology Campus, New Delhi 110020, IndiaIndians, a rapidly growing population, constitute vast genetic heterogeneity to that of Western population; however they have become a sedentary population in past decades due to rapid urbanization ensuing in the amplified prevalence of metabolic syndrome (MetS). We performed a genome-wide association study (GWAS) of MetS in 10,093 Indian individuals (6617 MetS and 3476 controls) of Indo-European origin, that belong to our previous biorepository of The Indian Diabetes Consortium (INDICO). The study was conducted in two stages—discovery phase (<i>N</i> = 2158) and replication phase (<i>N</i> = 7935). We discovered two variants within/near the <i>CETP</i> gene—rs1800775 and rs3816117—associated with MetS at genome-wide significance level during replication phase in Indians. Additional <i>CETP</i> loci rs7205804, rs1532624, rs3764261, rs247617, and rs173539 also cropped up as modest signals in Indians. Haplotype association analysis revealed GCCCAGC as the strongest haplotype within the <i>CETP</i> locus constituting all seven <i>CETP</i> signals. In combined analysis, we perceived a novel and functionally relevant sub-GWAS significant locus—rs16890462 in the vicinity of <i>SFRP1</i> gene. Overlaying gene regulatory data from ENCODE database revealed that single nucleotide polymorphism (SNP) rs16890462 resides in repressive chromatin in human subcutaneous adipose tissue as characterized by the enrichment of H3K27me3 and CTCF marks (repressive gene marks) and diminished H3K36me3 marks (activation gene marks). The variant displayed active DNA methylation marks in adipose tissue, suggesting its likely regulatory activity. Further, the variant also disrupts a potential binding site of a key transcription factor, NRF2, which is known for involvement in obesity and metabolic syndrome.https://www.mdpi.com/2218-273X/9/8/321genome wide association studymetabolic syndromegenetic variantsgene regulation |
| spellingShingle | Gauri Prasad Khushdeep Bandesh Anil K. Giri Yasmeen Kauser Prakriti Chanda Vaisak Parekatt INDICO Sandeep Mathur Sri Venkata Madhu Pradeep Venkatesh Anil Bhansali Raman K. Marwaha Analabha Basu Nikhil Tandon Dwaipayan Bharadwaj Genome-Wide Association Study of Metabolic Syndrome Reveals Primary Genetic Variants at <em>CETP</em> Locus in Indians Biomolecules genome wide association study metabolic syndrome genetic variants gene regulation |
| title | Genome-Wide Association Study of Metabolic Syndrome Reveals Primary Genetic Variants at <em>CETP</em> Locus in Indians |
| title_full | Genome-Wide Association Study of Metabolic Syndrome Reveals Primary Genetic Variants at <em>CETP</em> Locus in Indians |
| title_fullStr | Genome-Wide Association Study of Metabolic Syndrome Reveals Primary Genetic Variants at <em>CETP</em> Locus in Indians |
| title_full_unstemmed | Genome-Wide Association Study of Metabolic Syndrome Reveals Primary Genetic Variants at <em>CETP</em> Locus in Indians |
| title_short | Genome-Wide Association Study of Metabolic Syndrome Reveals Primary Genetic Variants at <em>CETP</em> Locus in Indians |
| title_sort | genome wide association study of metabolic syndrome reveals primary genetic variants at em cetp em locus in indians |
| topic | genome wide association study metabolic syndrome genetic variants gene regulation |
| url | https://www.mdpi.com/2218-273X/9/8/321 |
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