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

Monday,2022-10-10 14:50 America/Los_Angeles — ecterry
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-DI, 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, Cupples, AL, 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<p>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.</p>
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
75N92020D00005 / HL / NHLBI NIH HHS / United States
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
R01 HL046380 / HL / NHLBI NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
R01 NR008153 / NR / NINR NIH HHS / United States
HHSN268201600002C / HL / NHLBI NIH HHS / United States
R01 HL131136 / HL / NHLBI NIH HHS / United States
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R01 HL071259 / HL / NHLBI NIH HHS / United States
N01HC95163 / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
HHSN268201500001C / HL / NHLBI NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
HHSN268201600018C / HL / NHLBI NIH HHS / United States
HHSN268201800014I / HB / NHLBI NIH HHS / United States
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K99 AG066849 / AG / NIA NIH HHS / United States
K01 DK107836 / DK / NIDDK NIH HHS / United States
R01 HL087660 / HL / NHLBI NIH HHS / United States
T32 GM074905 / GM / NIGMS NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
U10 HL054464 / HL / NHLBI NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
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75N92020D00001 / HL / NHLBI NIH HHS / United States
U01 HL120393 / HL / NHLBI NIH HHS / United States
R01 HL113338 / HL / NHLBI NIH HHS / United States
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R01 ES029082 / ES / NIEHS NIH HHS / United States
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T32 HL129982 / HL / NHLBI NIH HHS / United States
U10 HL054457 / HL / NHLBI NIH HHS / United States
U01 HL084756 / HL / NHLBI NIH HHS / United States
R35 HL135818 / HL / NHLBI NIH HHS / United States
U10 HL054481 / HL / NHLBI NIH HHS / United States
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KL2 RR024990 / RR / NCRR NIH HHS / United States
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HHSN268201500003I / HL / NHLBI NIH HHS / United States
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HHSN268201700001C / HL / NHLBI NIH HHS / United States
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K01 HL130609 / HL / NHLBI NIH HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
R01 HL085571 / HL / NHLBI NIH HHS / United States
HHSN268201800015I / HB / NHLBI NIH HHS / United States
R01 HL071205 / HL / NHLBI NIH HHS / United States
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75N92019D00031 / HL / NHLBI NIH HHS / United States
HHSN268201700004C / HL / NHLBI NIH HHS / United States
UL1 TR000040 / TR / NCATS NIH HHS / United States
HHSN268201700002I / HL / NHLBI NIH HHS / United States
U01 HG009088 / HG / NHGRI NIH HHS / United States
UM1 DK078616 / DK / NIDDK NIH HHS / United States
R01 MH083824 / MH / NIMH NIH HHS / United States
HHSN268201800010I / HB / NHLBI NIH HHS / United States
HHSN268201700005I / HL / NHLBI NIH HHS / United States
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R01 AG023629 / AG / NIA NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
R01 HL092165 / HL / NHLBI NIH HHS / United States
R01 HL153814 / HL / NHLBI NIH HHS / United States
T32 HL007055 / HL / NHLBI NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States
R01 NS062059 / NS / NINDS NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
R01 HL090682 / HL / NHLBI NIH HHS / United States
HHSN268201800011I / HB / NHLBI NIH HHS / United States
HHSN268201700003I / HL / NHLBI NIH HHS / United States
R01 HG010297 / HG / NHGRI NIH HHS / United States
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R01 HL071258 / HL / NHLBI NIH HHS / United States
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U01 GM074518 / GM / NIGMS NIH HHS / United States
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R01 DK125403 / DK / NIDDK NIH HHS / United States
U01 HL054473 / HL / NHLBI NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
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K01 HL135405 / HL / NHLBI NIH HHS / United States
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ePub date: 
22/07

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