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Whole genome sequence association analysis of fasting glucose and fasting insulin levels in diverse cohorts from the NHLBI TOPMed program.

TitleWhole genome sequence association analysis of fasting glucose and fasting insulin levels in diverse cohorts from the NHLBI TOPMed program.
Publication TypeJournal Article
Year of Publication2022
AuthorsDiCorpo D, Gaynor SM, Russell EM, Westerman KE, Raffield LM, Majarian TD, Wu P, Sarnowski C, Highland HM, Jackson A, Hasbani NR, de Vries PS, Brody JA, Hidalgo B, Guo X, Perry JA, O'Connell JR, Lent S, Montasser ME, Cade BE, Jain D, Wang H, Albanus RD'Oliveira, Varshney A, Yanek LR, Lange L, Palmer ND, Almeida M, Peralta JM, Aslibekyan S, Baldridge AS, Bertoni AG, Bielak LF, Chen C-S, Chen Y-D I, Choi WJung, Goodarzi MO, Floyd JS, Irvin MR, Kalyani RR, Kelly TN, Lee S, Liu C-T, Loesch D, Manson JAE, Minster RL, Naseri T, Pankow JS, Rasmussen-Torvik LJ, Reiner AP, Reupena M'aSefuiva, Selvin E, Smith JA, Weeks DE, Xu H, Yao J, Zhao W, Parker S, Alonso A, Arnett DK, Blangero J, Boerwinkle E, Correa A, L Cupples A, Curran JE, Duggirala R, He J, Heckbert SR, Kardia SLR, Kim RW, Kooperberg C, Liu S, Mathias RA, McGarvey ST, Mitchell BD, Morrison AC, Peyser PA, Psaty BM, Redline S, Shuldiner AR, Taylor KD, Vasan RS, Viaud-Martinez KA, Florez JC, Wilson JG, Sladek R, Rich SS, Rotter JI, Lin X, Dupuis J, Meigs JB, Wessel J, Manning AK
JournalCommun Biol
Volume5
Issue1
Pagination756
Date Published2022 07 28
ISSN2399-3642
KeywordsDiabetes Mellitus, Type 2, Fasting, Glucose, Humans, Insulin, National Heart, Lung, and Blood Institute (U.S.), Nerve Tissue Proteins, Polymorphism, Single Nucleotide, Precision Medicine, Receptors, Immunologic, United States
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.

DOI10.1038/s42003-022-03702-4
Alternate JournalCommun Biol
PubMed ID35902682
PubMed Central IDPMC9334637
Grant ListR01 HL071250 / HL / NHLBI NIH HHS / United States
U01 HL054472 / HL / NHLBI NIH HHS / United States
R01 HL071025 / HL / NHLBI NIH HHS / United States
UL1 RR033176 / RR / NCRR NIH HHS / United States
R01 HL112064 / HL / NHLBI NIH HHS / United States
K24 DK110550 / DK / NIDDK NIH HHS / United States
75N92020D00002 / HL / NHLBI NIH HHS / United States
HHSN268201500003C / HL / NHLBI NIH HHS / United States
R01 HL113323 / HL / NHLBI NIH HHS / United States
HHSN268201800012I / HB / NHLBI NIH HHS / United States
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R01 HL104135 / HL / NHLBI NIH HHS / United States
R35 CA197449 / CA / NCI NIH HHS / United States
HHSN268201800012C / HL / NHLBI NIH HHS / United States
N01HC95160 / HL / NHLBI NIH HHS / United States
R01 HL071251 / HL / NHLBI NIH HHS / United States
R01 HL133040 / HL / NHLBI NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
R01 HL087698 / HL / NHLBI NIH HHS / United States
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