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

Huang, Jie1; Huffman, Jennifer E.2; Huang, Yunfeng3,4; Do Valle, Italo5,6,7; Assimes, Themistocles L.8,9; Raghavan, Sridharan10,11; Voight, Benjamin F.12,13,14,15; Liu, Chang3; Barabasi, Albert-Laszlo5,6,16,17; Huang, Rose D. L.2; Hui, Qin3,4; Nguyen, Xuan-Mai T.18,19; Ho, Yuk-Lam19; Djousse, Luc19,20; Lynch, Julie A.21,22; Vujkovic, Marijana12,23; Tcheandjieu, Catherine8,9; Tang, Hua8,24; Damrauer, Scott M.12,25,26; Reaven, Peter D.27,28; Miller, Donald29; Phillips, Lawrence S.4,30; Ng, Maggie C. Y.31,32; Graff, Mariaelisa33; Haiman, Christopher A.34; Loos, Ruth J. F.35,36,37; North, Kari E.33; Yengo, Loic38; Smith, George Davey39,40; Saleheen, Danish41,42,43; Gaziano, J. Michael19,20; Rader, Daniel J.23,26; Tsao, Philip S.8,9; Cho, Kelly19,20; Chang, Kyong-Mi12,23; Wilson, Peter W. F.3,4,44; Sun, Yan, V3,4; O'Donnell, Christopher J.2,20,45

2022-12-29

10.1038/s41467-022-35553-2

NATURE COMMUNICATIONS   Impact Factor & Quartile

2041-1723

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 similar to 1.1 million) and African (N similar to 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.

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Department of Veterans Affairs Office of Research and Development, Million Veteran Program["I01-BX003340","I01-BX004821"] ; NIH["R01DK110113","R01DK075787","R01DK107786","1P01HL132825"] ; Novo Nordisk Foundation[190503] ; Australian Research Council[DE200100425] ; Department of Veterans Affairs[36C24122N0769] ; European Union[810115 - DYNASNET] ; Medical Research Council[MC_UU_00011/1] ; [R01 NR013520] ; [R01 DK101478] ; [DK126194] ; [IK2-CX001780]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000905913700005

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Web of Science

1.Southern Univ Sci & Technol, Sch Publ Hlth & Emergency Management, Shenzhen, Guangdong, Peoples R China
2.VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, Ctr Populat Genom, Boston, MA 02130 USA
3.Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA
4.Atlanta VA Hlth Care Syst, Decatur, GA 30033 USA
5.Northeastern Univ, Network Sci Inst, Boston, MA 02115 USA
6.Northeastern Univ, Dept Phys, Boston, MA 02115 USA
7.VA Boston Healthcare Syst, MAVERIC, Div Populat Hlth & Data Sci, Boston, MA USA
8.VA Palo Alto Hlth Care Syst, Palo Alto, CA USA
9.Stanford Univ, Dept Med, Sch Med, Stanford, CA USA
10.VA Eastern Colorado Healthcare Syst, Aurora, CO USA
11.Univ Colorado, Sch Med, Aurora, CO USA
12.Corporal Michael J Crescenz VA Med Ctr, Philadelphia, PA USA
13.Univ Penn, Dept Syst Pharmacol & Translat Therapeut, Philadelphia, PA 19104 USA
14.Univ Penn, Dept Genet, Philadelphia, PA 19104 USA
15.Univ Penn, Inst Translat Med & Therapeut, Perelman Sch Med, Philadelphia, PA 19104 USA
16.Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA USA
17.Cent European Univ, Dept Network & Data Sci, Budapest, Hungary
18.Carle Illinois Coll Med, Champaign, IL USA
19.VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, Boston, MA USA
20.Harvard Med Sch, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA
21.VA Salt Lake City Healthcare, Salt Lake City, UT USA
22.Univ Massachusetts, Boston, MA 02125 USA
23.Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA
24.Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA
25.Univ Penn, Dept Surg, Perelman Sch Med, Philadelphia, PA 19104 USA
26.Univ Penn, Dept Genet, Perelman Sch Med, Philadelphia, PA USA
27.Phoenix VA Hlth Care Syst, Phoenix, AZ USA
28.Univ Arizona, Coll Med, Phoenix, AZ USA
29.Bedford VA Med Ctr, Ctr Healthcare Org & Implementat Res, Bedford, MA USA
30.Emory Univ, Sch Med, Dept Med, Div Endocrinol, Atlanta, GA USA
31.Vanderbilt Univ Sch Med, Vanderbilt Genet Inst, Nashville, TN USA
32.Vanderbilt Univ Sch Med, Div Genet Med, Nashville, TN USA
33.Univ North Carolina Chapel Hill, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA
34.Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA
35.Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA
36.Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA
37.Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Fac Hlth & Med Sci, Copenhagen, Denmark
38.Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia
39.Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol, Avon, England
40.Univ Bristol, Med Res Council Integrat Epidemiol Unit, Bristol, Avon, England
41.Ctr Noncommunicable Dis, Karachi, Sindh, Pakistan
42.Columbia Univ, Dept Med, Irving Med Ctr, New York, NY USA
43.Columbia Univ, Dept Cardiol, Irving Med Ctr, New York, NY USA
44.Emory Univ, Div Cardiol, Sch Med, Atlanta, GA USA
45.VA Boston Healthcare Syst, Cardiol Sect, Boston, MA 02130 USA

Huang, Jie,Huffman, Jennifer E.,Huang, Yunfeng,et al. Genomics and phenomics of body mass index reveals a complex disease network[J]. NATURE COMMUNICATIONS,2022,13(1).

Huang, Jie.,Huffman, Jennifer E..,Huang, Yunfeng.,Do Valle, Italo.,Assimes, Themistocles L..,...&O'Donnell, Christopher J..(2022).Genomics and phenomics of body mass index reveals a complex disease network.NATURE COMMUNICATIONS,13(1).

Huang, Jie,et al."Genomics and phenomics of body mass index reveals a complex disease network".NATURE COMMUNICATIONS 13.1(2022).