1. Whole genome sequence association analysis of fasting glucose and fasting insulin levels in diverse cohorts from the NHLBI TOPMed program
- Author
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Daniel DiCorpo, Sheila M. Gaynor, Emily M. Russell, Kenneth E. Westerman, Laura M. Raffield, Timothy D. Majarian, Peitao Wu, Chloé Sarnowski, Heather M. Highland, Anne Jackson, Natalie R. Hasbani, Paul S. de Vries, Jennifer A. Brody, Bertha Hidalgo, Xiuqing Guo, James A. Perry, Jeffrey R. O’Connell, Samantha Lent, May E. Montasser, Brian E. Cade, Deepti Jain, Heming Wang, Ricardo D’Oliveira Albanus, Arushi Varshney, Lisa R. Yanek, Leslie Lange, Nicholette D. Palmer, Marcio Almeida, Juan M. Peralta, Stella Aslibekyan, Abigail S. Baldridge, Alain G. Bertoni, Lawrence F. Bielak, Chung-Shiuan Chen, Yii-Der Ida Chen, Won Jung Choi, Mark O. Goodarzi, James S. Floyd, Marguerite R. Irvin, Rita R. Kalyani, Tanika N. Kelly, Seonwook Lee, Ching-Ti Liu, Douglas Loesch, JoAnn E. Manson, Ryan L. Minster, Take Naseri, James S. Pankow, Laura J. Rasmussen-Torvik, Alexander P. Reiner, Muagututi’a Sefuiva Reupena, Elizabeth Selvin, Jennifer A. Smith, Daniel E. Weeks, Huichun Xu, Jie Yao, Wei Zhao, Stephen Parker, Alvaro Alonso, Donna K. Arnett, John Blangero, Eric Boerwinkle, Adolfo Correa, L. Adrienne Cupples, Joanne E. Curran, Ravindranath Duggirala, Jiang He, Susan R. Heckbert, Sharon L. R. Kardia, Ryan W. Kim, Charles Kooperberg, Simin Liu, Rasika A. Mathias, Stephen T. McGarvey, Braxton D. Mitchell, Alanna C. Morrison, Patricia A. Peyser, Bruce M. Psaty, Susan Redline, Alan R. Shuldiner, Kent D. Taylor, Ramachandran S. Vasan, Karine A. Viaud-Martinez, Jose C. Florez, James G. Wilson, Robert Sladek, Stephen S. Rich, Jerome I. Rotter, Xihong Lin, Josée Dupuis, James B. Meigs, Jennifer Wessel, and Alisa K. Manning
- Subjects
Medicine (miscellaneous) ,Nerve Tissue Proteins ,Polymorphism, Single Nucleotide ,General Biochemistry, Genetics and Molecular Biology ,Immunologic ,Receptors ,and Blood Institute (U.S.) ,Diabetes Mellitus ,Genetics ,Humans ,Insulin ,2.1 Biological and endogenous factors ,Receptors, Immunologic ,Polymorphism ,Precision Medicine ,Aetiology ,Lung ,Metabolic and endocrine ,Diabetes ,Human Genome ,Fasting ,Single Nucleotide ,National Heart ,United States ,Glucose ,Good Health and Well Being ,Diabetes Mellitus, Type 2 ,National Heart, Lung, and Blood Institute (U.S.) ,General Agricultural and Biological Sciences ,Type 2 ,Biotechnology - Abstract
The genetic determinants of fasting glucose (FG) and fasting insulin (FI) have been studied mostly through genome arrays, resulting in over 100 associated variants. We extended this work with high-coverage whole genome sequencing analyses from fifteen cohorts in NHLBI’s Trans-Omics for Precision Medicine (TOPMed) program. Over 23,000 non-diabetic individuals from five race-ethnicities/populations (African, Asian, European, Hispanic and Samoan) were included. Eight variants were significantly associated with FG or FI across previously identified regions MTNR1B, G6PC2, GCK, GCKR and FOXA2. We additionally characterize suggestive associations with FG or FI near previously identified SLC30A8, TCF7L2, and ADCY5 regions as well as APOB, PTPRT, and ROBO1. Functional annotation resources including the Diabetes Epigenome Atlas were compiled for each signal (chromatin states, annotation principal components, and others) to elucidate variant-to-function hypotheses. We provide a catalog of nucleotide-resolution genomic variation spanning intergenic and intronic regions creating a foundation for future sequencing-based investigations of glycemic traits.
- Published
- 2022
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