Genomics and phenomics of body mass index reveals a complex disease network

Research output: Contribution to journal › Journal article › Research › peer-review

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Genomics and phenomics of body mass index reveals a complex disease network. / Huang, Jie; Huffman, Jennifer E.; Huang, Yunfeng; Do Valle, Ítalo; Assimes, Themistocles L.; Raghavan, Sridharan; Voight, Benjamin F.; Liu, Chang; Barabási, Albert László; Huang, Rose D.L.; Hui, Qin; Nguyen, Xuan Mai T.; Ho, Yuk Lam; Djousse, Luc; Lynch, Julie A.; Vujkovic, Marijana; Tcheandjieu, Catherine; Tang, Hua; Damrauer, Scott M.; Reaven, Peter D.; Miller, Donald; Phillips, Lawrence S.; Ng, Maggie C.Y.; Graff, Mariaelisa; Haiman, Christopher A.; Loos, Ruth J.F.; North, Kari E.; Yengo, Loic; Smith, George Davey; Saleheen, Danish; Gaziano, J. Michael; Rader, Daniel J.; Tsao, Philip S.; Cho, Kelly; Chang, Kyong Mi; Wilson, Peter W.F.; Sun, Yan V.; O’Donnell, Christopher J.; VA Million Veteran Program.

In: Nature Communications, Vol. 13, No. 1, 7973, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Huang, J, Huffman, JE, Huang, Y, Do Valle, Í, Assimes, TL, Raghavan, S, Voight, BF, Liu, C, Barabási, AL, Huang, RDL, Hui, Q, Nguyen, XMT, Ho, YL, Djousse, L, Lynch, JA, Vujkovic, M, Tcheandjieu, C, Tang, H, Damrauer, SM, Reaven, PD, Miller, D, Phillips, LS, Ng, MCY, Graff, M, Haiman, CA, Loos, RJF, North, KE, Yengo, L, Smith, GD, Saleheen, D, Gaziano, JM, Rader, DJ, Tsao, PS, Cho, K, Chang, KM, Wilson, PWF, Sun, YV, O’Donnell, CJ & VA Million Veteran Program 2022, 'Genomics and phenomics of body mass index reveals a complex disease network', Nature Communications, vol. 13, no. 1, 7973. https://doi.org/10.1038/s41467-022-35553-2

APA

Huang, J., Huffman, J. E., Huang, Y., Do Valle, Í., Assimes, T. L., Raghavan, S., Voight, B. F., Liu, C., Barabási, A. L., Huang, R. D. L., Hui, Q., Nguyen, X. M. T., Ho, Y. L., Djousse, L., Lynch, J. A., Vujkovic, M., Tcheandjieu, C., Tang, H., Damrauer, S. M., ... VA Million Veteran Program (2022). Genomics and phenomics of body mass index reveals a complex disease network. Nature Communications, 13(1), [7973]. https://doi.org/10.1038/s41467-022-35553-2

Vancouver

Huang J, Huffman JE, Huang Y, Do Valle Í, Assimes TL, Raghavan S et al. Genomics and phenomics of body mass index reveals a complex disease network. Nature Communications. 2022;13(1). 7973. https://doi.org/10.1038/s41467-022-35553-2

Author

Huang, Jie ; Huffman, Jennifer E. ; Huang, Yunfeng ; Do Valle, Ítalo ; Assimes, Themistocles L. ; Raghavan, Sridharan ; Voight, Benjamin F. ; Liu, Chang ; Barabási, Albert László ; Huang, Rose D.L. ; Hui, Qin ; Nguyen, Xuan Mai T. ; Ho, Yuk Lam ; Djousse, Luc ; Lynch, Julie A. ; Vujkovic, Marijana ; Tcheandjieu, Catherine ; Tang, Hua ; Damrauer, Scott M. ; Reaven, Peter D. ; Miller, Donald ; Phillips, Lawrence S. ; Ng, Maggie C.Y. ; Graff, Mariaelisa ; Haiman, Christopher A. ; Loos, Ruth J.F. ; North, Kari E. ; Yengo, Loic ; Smith, George Davey ; Saleheen, Danish ; Gaziano, J. Michael ; Rader, Daniel J. ; Tsao, Philip S. ; Cho, Kelly ; Chang, Kyong Mi ; Wilson, Peter W.F. ; Sun, Yan V. ; O’Donnell, Christopher J. ; VA Million Veteran Program. / Genomics and phenomics of body mass index reveals a complex disease network. In: Nature Communications. 2022 ; Vol. 13, No. 1.

Bibtex

@article{16ae318f00ea40ed88bddcc7a7c4eabc,
title = "Genomics and phenomics of body mass index reveals a complex disease network",
abstract = "Elevated body mass index (BMI) is heritable and associated with many health conditions that impact morbidity and mortality. The study of the genetic association of BMI across a broad range of common disease conditions offers the opportunity to extend current knowledge regarding the breadth and depth of adiposity-related diseases. We identify 906 (364 novel) and 41 (6 novel) genome-wide significant loci for BMI among participants of European (N~1.1 million) and African (N~100,000) ancestry, respectively. Using a BMI genetic risk score including 2446 variants, 316 diagnoses are associated in the Million Veteran Program, with 96.5% showing increased risk. A co-morbidity network analysis reveals seven disease communities containing multiple interconnected diseases associated with BMI as well as extensive connections across communities. Mendelian randomization analysis confirms numerous phenotypes across a breadth of organ systems, including conditions of the circulatory (heart failure, ischemic heart disease, atrial fibrillation), genitourinary (chronic renal failure), respiratory (respiratory failure, asthma), musculoskeletal and dermatologic systems that are deeply interconnected within and across the disease communities. This work shows that the complex genetic architecture of BMI associates with a broad range of major health conditions, supporting the need for comprehensive approaches to prevent and treat obesity.",
author = "Jie Huang and Huffman, {Jennifer E.} and Yunfeng Huang and {Do Valle}, {\'I}talo and Assimes, {Themistocles L.} and Sridharan Raghavan and Voight, {Benjamin F.} and Chang Liu and Barab{\'a}si, {Albert L{\'a}szl{\'o}} and Huang, {Rose D.L.} and Qin Hui and Nguyen, {Xuan Mai T.} and Ho, {Yuk Lam} and Luc Djousse and Lynch, {Julie A.} and Marijana Vujkovic and Catherine Tcheandjieu and Hua Tang and Damrauer, {Scott M.} and Reaven, {Peter D.} and Donald Miller and Phillips, {Lawrence S.} and Ng, {Maggie C.Y.} and Mariaelisa Graff and Haiman, {Christopher A.} and Loos, {Ruth J.F.} and North, {Kari E.} and Loic Yengo and Smith, {George Davey} and Danish Saleheen and Gaziano, {J. Michael} and Rader, {Daniel J.} and Tsao, {Philip S.} and Kelly Cho and Chang, {Kyong Mi} and Wilson, {Peter W.F.} and Sun, {Yan V.} and O{\textquoteright}Donnell, {Christopher J.} and {VA Million Veteran Program}",
note = "Publisher Copyright: {\textcopyright} 2022, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.",
year = "2022",
doi = "10.1038/s41467-022-35553-2",
language = "English",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - Genomics and phenomics of body mass index reveals a complex disease network

AU - Huang, Jie

AU - Huffman, Jennifer E.

AU - Huang, Yunfeng

AU - Do Valle, Ítalo

AU - Assimes, Themistocles L.

AU - Raghavan, Sridharan

AU - Voight, Benjamin F.

AU - Liu, Chang

AU - Barabási, Albert László

AU - Huang, Rose D.L.

AU - Hui, Qin

AU - Nguyen, Xuan Mai T.

AU - Ho, Yuk Lam

AU - Djousse, Luc

AU - Lynch, Julie A.

AU - Vujkovic, Marijana

AU - Tcheandjieu, Catherine

AU - Tang, Hua

AU - Damrauer, Scott M.

AU - Reaven, Peter D.

AU - Miller, Donald

AU - Phillips, Lawrence S.

AU - Ng, Maggie C.Y.

AU - Graff, Mariaelisa

AU - Haiman, Christopher A.

AU - Loos, Ruth J.F.

AU - North, Kari E.

AU - Yengo, Loic

AU - Smith, George Davey

AU - Saleheen, Danish

AU - Gaziano, J. Michael

AU - Rader, Daniel J.

AU - Tsao, Philip S.

AU - Cho, Kelly

AU - Chang, Kyong Mi

AU - Wilson, Peter W.F.

AU - Sun, Yan V.

AU - O’Donnell, Christopher J.

AU - VA Million Veteran Program

N1 - Publisher Copyright: © 2022, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

PY - 2022

Y1 - 2022

N2 - Elevated body mass index (BMI) is heritable and associated with many health conditions that impact morbidity and mortality. The study of the genetic association of BMI across a broad range of common disease conditions offers the opportunity to extend current knowledge regarding the breadth and depth of adiposity-related diseases. We identify 906 (364 novel) and 41 (6 novel) genome-wide significant loci for BMI among participants of European (N~1.1 million) and African (N~100,000) ancestry, respectively. Using a BMI genetic risk score including 2446 variants, 316 diagnoses are associated in the Million Veteran Program, with 96.5% showing increased risk. A co-morbidity network analysis reveals seven disease communities containing multiple interconnected diseases associated with BMI as well as extensive connections across communities. Mendelian randomization analysis confirms numerous phenotypes across a breadth of organ systems, including conditions of the circulatory (heart failure, ischemic heart disease, atrial fibrillation), genitourinary (chronic renal failure), respiratory (respiratory failure, asthma), musculoskeletal and dermatologic systems that are deeply interconnected within and across the disease communities. This work shows that the complex genetic architecture of BMI associates with a broad range of major health conditions, supporting the need for comprehensive approaches to prevent and treat obesity.

AB - Elevated body mass index (BMI) is heritable and associated with many health conditions that impact morbidity and mortality. The study of the genetic association of BMI across a broad range of common disease conditions offers the opportunity to extend current knowledge regarding the breadth and depth of adiposity-related diseases. We identify 906 (364 novel) and 41 (6 novel) genome-wide significant loci for BMI among participants of European (N~1.1 million) and African (N~100,000) ancestry, respectively. Using a BMI genetic risk score including 2446 variants, 316 diagnoses are associated in the Million Veteran Program, with 96.5% showing increased risk. A co-morbidity network analysis reveals seven disease communities containing multiple interconnected diseases associated with BMI as well as extensive connections across communities. Mendelian randomization analysis confirms numerous phenotypes across a breadth of organ systems, including conditions of the circulatory (heart failure, ischemic heart disease, atrial fibrillation), genitourinary (chronic renal failure), respiratory (respiratory failure, asthma), musculoskeletal and dermatologic systems that are deeply interconnected within and across the disease communities. This work shows that the complex genetic architecture of BMI associates with a broad range of major health conditions, supporting the need for comprehensive approaches to prevent and treat obesity.

U2 - 10.1038/s41467-022-35553-2

DO - 10.1038/s41467-022-35553-2

M3 - Journal article

C2 - 36581621

AN - SCOPUS:85145152971

VL - 13

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 7973

ER -

ID: 335676711