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

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; Jo Ann 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; Alisa K. Manning

doi:10.1038/s42003-022-03702-4

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

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. CadeDeepti 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, Jo Ann 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, Alisa K. Manning

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	756
Journal	Communications biology
Volume	5
Issue number	1
DOIs	https://doi.org/10.1038/s42003-022-03702-4
State	Published - Dec 2022

ASJC Scopus subject areas

General Agricultural and Biological Sciences
General Biochemistry, Genetics and Molecular Biology
Medicine (miscellaneous)

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DiCorpo, D., Gaynor, S. M., Russell, E. M., Westerman, K. E., Raffield, L. M., Majarian, T. D., Wu, P., Sarnowski, C., Highland, H. M., Jackson, A., Hasbani, N. R., de Vries, P. S., Brody, J. A., Hidalgo, B., Guo, X., Perry, J. A., O’Connell, J. R., Lent, S., Montasser, M. E., ... Manning, A. K. (2022). Whole genome sequence association analysis of fasting glucose and fasting insulin levels in diverse cohorts from the NHLBI TOPMed program. Communications biology, 5(1), Article 756. https://doi.org/10.1038/s42003-022-03702-4

DiCorpo, 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, D’Oliveira Albanus, R, Varshney, A, Yanek, LR, Lange, L, Palmer, ND, Almeida, M, Peralta, JM, Aslibekyan, S, Baldridge, AS, Bertoni, AG, Bielak, LF, Chen, CS, Chen, YDI, Choi, WJ, Goodarzi, MO, Floyd, JS, Irvin, MR, Kalyani, RR, Kelly, TN, Lee, S, Liu, CT, Loesch, D, Manson, JAE, Minster, RL, Naseri, T, Pankow, JS, Rasmussen-Torvik, LJ, Reiner, AP, Reupena, MS, 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, LA, 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 2022, 'Whole genome sequence association analysis of fasting glucose and fasting insulin levels in diverse cohorts from the NHLBI TOPMed program', Communications biology, vol. 5, no. 1, 756. https://doi.org/10.1038/s42003-022-03702-4

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title = "Whole genome sequence association analysis of fasting glucose and fasting insulin levels in diverse cohorts from the NHLBI TOPMed program",

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{\textquoteright}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.",

author = "Daniel DiCorpo and Gaynor, {Sheila M.} and Russell, {Emily M.} and Westerman, {Kenneth E.} and Raffield, {Laura M.} and Majarian, {Timothy D.} and Peitao Wu and Chlo{\'e} Sarnowski and Highland, {Heather M.} and Anne Jackson and Hasbani, {Natalie R.} and {de Vries}, {Paul S.} and Brody, {Jennifer A.} and Bertha Hidalgo and Xiuqing Guo and Perry, {James A.} and O{\textquoteright}Connell, {Jeffrey R.} and Samantha Lent and Montasser, {May E.} and Cade, {Brian E.} and Deepti Jain and Heming Wang and {D{\textquoteright}Oliveira Albanus}, Ricardo and Arushi Varshney and Yanek, {Lisa R.} and Leslie Lange and Palmer, {Nicholette D.} and Marcio Almeida and Peralta, {Juan M.} and Stella Aslibekyan and Baldridge, {Abigail S.} and Bertoni, {Alain G.} and Bielak, {Lawrence F.} and Chen, {Chung Shiuan} and Chen, {Yii Der Ida} and Choi, {Won Jung} and Goodarzi, {Mark O.} and Floyd, {James S.} and Irvin, {Marguerite R.} and Kalyani, {Rita R.} and Kelly, {Tanika N.} and Seonwook Lee and Liu, {Ching Ti} and Douglas Loesch and Manson, {Jo Ann E.} and Minster, {Ryan L.} and Take Naseri and Pankow, {James S.} and Rasmussen-Torvik, {Laura J.} and Reiner, {Alexander P.} and Reupena, {Muagututi{\textquoteright}a Sefuiva} and Elizabeth Selvin and Smith, {Jennifer A.} and Weeks, {Daniel E.} and Huichun Xu and Jie Yao and Wei Zhao and Stephen Parker and Alvaro Alonso and Arnett, {Donna K.} and John Blangero and Eric Boerwinkle and Adolfo Correa and Cupples, {L. Adrienne} and Curran, {Joanne E.} and Ravindranath Duggirala and Jiang He and Heckbert, {Susan R.} and Kardia, {Sharon L.R.} and Kim, {Ryan W.} and Charles Kooperberg and Simin Liu and Mathias, {Rasika A.} and McGarvey, {Stephen T.} and Mitchell, {Braxton D.} and Morrison, {Alanna C.} and Peyser, {Patricia A.} and Psaty, {Bruce M.} and Susan Redline and Shuldiner, {Alan R.} and Taylor, {Kent D.} and Vasan, {Ramachandran S.} and Viaud-Martinez, {Karine A.} and Florez, {Jose C.} and Wilson, {James G.} and Robert Sladek and Rich, {Stephen S.} and Rotter, {Jerome I.} and Xihong Lin and Jos{\'e}e Dupuis and Meigs, {James B.} and Jennifer Wessel and Manning, {Alisa K.}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s42003-022-03702-4",

language = "English (US)",

volume = "5",

journal = "Communications biology",

issn = "2399-3642",

publisher = "Springer Nature",

number = "1",

}

TY - JOUR

T1 - Whole genome sequence association analysis of fasting glucose and fasting insulin levels in diverse cohorts from the NHLBI TOPMed program

AU - DiCorpo, Daniel

AU - Gaynor, Sheila M.

AU - Russell, Emily M.

AU - Westerman, Kenneth E.

AU - Raffield, Laura M.

AU - Majarian, Timothy D.

AU - Wu, Peitao

AU - Sarnowski, Chloé

AU - Highland, Heather M.

AU - Jackson, Anne

AU - Hasbani, Natalie R.

AU - de Vries, Paul S.

AU - Brody, Jennifer A.

AU - Hidalgo, Bertha

AU - Guo, Xiuqing

AU - Perry, James A.

AU - O’Connell, Jeffrey R.

AU - Lent, Samantha

AU - Montasser, May E.

AU - Cade, Brian E.

AU - Jain, Deepti

AU - Wang, Heming

AU - D’Oliveira Albanus, Ricardo

AU - Varshney, Arushi

AU - Yanek, Lisa R.

AU - Lange, Leslie

AU - Palmer, Nicholette D.

AU - Almeida, Marcio

AU - Peralta, Juan M.

AU - Aslibekyan, Stella

AU - Baldridge, Abigail S.

AU - Bertoni, Alain G.

AU - Bielak, Lawrence F.

AU - Chen, Chung Shiuan

AU - Chen, Yii Der Ida

AU - Choi, Won Jung

AU - Goodarzi, Mark O.

AU - Floyd, James S.

AU - Irvin, Marguerite R.

AU - Kalyani, Rita R.

AU - Kelly, Tanika N.

AU - Lee, Seonwook

AU - Liu, Ching Ti

AU - Loesch, Douglas

AU - Manson, Jo Ann E.

AU - Minster, Ryan L.

AU - Naseri, Take

AU - Pankow, James S.

AU - Rasmussen-Torvik, Laura J.

AU - Reiner, Alexander P.

AU - Reupena, Muagututi’a Sefuiva

AU - Selvin, Elizabeth

AU - Smith, Jennifer A.

AU - Weeks, Daniel E.

AU - Xu, Huichun

AU - Yao, Jie

AU - Zhao, Wei

AU - Parker, Stephen

AU - Alonso, Alvaro

AU - Arnett, Donna K.

AU - Blangero, John

AU - Boerwinkle, Eric

AU - Correa, Adolfo

AU - Cupples, L. Adrienne

AU - Curran, Joanne E.

AU - Duggirala, Ravindranath

AU - He, Jiang

AU - Heckbert, Susan R.

AU - Kardia, Sharon L.R.

AU - Kim, Ryan W.

AU - Kooperberg, Charles

AU - Liu, Simin

AU - Mathias, Rasika A.

AU - McGarvey, Stephen T.

AU - Mitchell, Braxton D.

AU - Morrison, Alanna C.

AU - Peyser, Patricia A.

AU - Psaty, Bruce M.

AU - Redline, Susan

AU - Shuldiner, Alan R.

AU - Taylor, Kent D.

AU - Vasan, Ramachandran S.

AU - Viaud-Martinez, Karine A.

AU - Florez, Jose C.

AU - Wilson, James G.

AU - Sladek, Robert

AU - Rich, Stephen S.

AU - Rotter, Jerome I.

AU - Lin, Xihong

AU - Dupuis, Josée

AU - Meigs, James B.

AU - Wessel, Jennifer

AU - Manning, Alisa K.

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

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UR - http://www.scopus.com/inward/citedby.url?scp=85135161405&partnerID=8YFLogxK

U2 - 10.1038/s42003-022-03702-4

DO - 10.1038/s42003-022-03702-4

M3 - Article

C2 - 35902682

AN - SCOPUS:85135161405

SN - 2399-3642

VL - 5

JO - Communications biology

JF - Communications biology

IS - 1

M1 - 756

ER -

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

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