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Genome-wide association study of blood lipids in Indians confirms universality of established variants

Authors
  • Bandesh, Khushdeep1, 2
  • Prasad, Gauri1, 2
  • Giri, Anil K.1, 2
  • Kauser, Yasmeen1, 2
  • Upadhyay, Medha3
  • Basu, Analabha4
  • Tandon, Nikhil5
  • Bharadwaj, Dwaipayan2, 3
  • 1 Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, New Delhi, 110020, India , New Delhi (India)
  • 2 Academy of Scientific and Innovative Research, CSIR-Institute of Genomics and Integrative Biology Campus, New Delhi, 110020, India , New Delhi (India)
  • 3 Jawaharlal Nehru University, Systems Genomics Laboratory, School of Biotechnology, New Delhi, 110067, India , New Delhi (India)
  • 4 National Institute of Biomedical Genomics, P.O.: Netaji Subhas Sanatorium, Kalyani, West Bengal, 741251, India , Kalyani (India)
  • 5 All India Institute of Medical Sciences, Department of Endocrinology and Metabolism, New Delhi, 110029, India , New Delhi (India)
Type
Published Article
Journal
Journal of Human Genetics
Publisher
Springer Nature
Publication Date
Mar 25, 2019
Volume
64
Issue
6
Pages
573–587
Identifiers
DOI: 10.1038/s10038-019-0591-7
Source
Springer Nature
License
Yellow

Abstract

Lipids foster energy production and their altered levels have been coupled with metabolic ailments. Indians feature high prevalence of metabolic diseases, yet uncharacterized for genes regulating lipid homeostasis. We performed first GWAS for quantitative lipids (total cholesterol, LDL, HDL, and triglycerides) exclusively in 5271 Indians. Further to corroborate our genetic findings, we investigated DNA methylation marks in peripheral blood in Indians at the identified loci (N = 233) and retrieved gene regulatory features from public domains. Recurrent GWAS loci—CELSR2, CETP, LPL, ZNF259, and BUD13 cropped up as lead signals in Indians, reflecting their universal applicability. Besides established variants, we found certain unreported variants at sub-genome-wide level—QKI, REEP3, TMCC2, FAM129C, FAM241B, and LOC100506207. These variants though failed to attain GWAS significance in Indians, but largely turned out to be active CpG sites in human subcutaneous adipose tissue and showed robust association to two or more lipid traits. Of which, QKI variants showed significant association to all four lipid traits and their designated region was observed to be a key gene regulatory segment denoting active transcription particularly in human subcutaneous adipose tissue. Both established and novel loci were observed to be significantly associated with altered DNA methylation in Indians for specific CpGs that resided in key regulatory elements. Further, gene-based association analysis pinpointed novel GWAS loci—LINC01340 and IQCJ-SCHIP1 for TC; IFT27, IFT88, and LINC02141 for HDL; and TEX26 for TG. Present study ascertains universality of selected known genes and also identifies certain novel loci for lipids in Indians by integrating data from various levels of gene regulation.

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