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

被引：66

作者：

Huang, Jie ^{[1
]}

Huffman, Jennifer E. ^{[2
]}

Huang, Yunfeng ^{[3
,4
]}

Do Valle, Italo ^{[5
,6
,7
]}

Assimes, Themistocles L. ^{[8
,9
]}

Raghavan, Sridharan ^{[10
,11
]}

Voight, Benjamin F. ^{[12
,13
,14
,15
]}

Liu, Chang ^{[3
]}

Barabasi, Albert-Laszlo ^{[5
,6
,16
,17
]}

Huang, Rose D. L. ^{[2
]}

Hui, Qin ^{[3
,4
]}

Nguyen, Xuan-Mai T. ^{[18
,19
]}

Ho, Yuk-Lam ^{[19
]}

Djousse, Luc ^{[19
,20
]}

Lynch, Julie A. ^{[21
,22
]}

Vujkovic, Marijana ^{[12
,23
]}

Tcheandjieu, Catherine ^{[8
,9
]}

Tang, Hua ^{[8
,24
]}

Damrauer, Scott M. ^{[12
,25
,26
]}

Reaven, Peter D. ^{[27
,28
]}

Miller, Donald ^{[29
]}

Phillips, Lawrence S. ^{[4
,30
]}

Ng, Maggie C. Y. ^{[31
,32
]}

Graff, Mariaelisa ^{[33
]}

Haiman, Christopher A. ^{[34
]}

Loos, Ruth J. F. ^{[35
,36
,37
]}

North, Kari E. ^{[33
]}

Yengo, Loic ^{[38
]}

Smith, George Davey ^{[39
,40
]}

Saleheen, Danish ^{[41
,42
,43
]}

Gaziano, J. Michael ^{[19
,20
]}

Rader, Daniel J. ^{[23
,26
]}

Tsao, Philip S. ^{[8
,9
]}

Cho, Kelly ^{[19
,20
]}

Chang, Kyong-Mi ^{[12
,23
]}

Wilson, Peter W. F. ^{[3
,4
,44
]}

Sun, Yan, V ^{[3
,4
]}

O'Donnell, Christopher J. ^{[2
,20
,45
]}

机构：

[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

来源：

NATURE COMMUNICATIONS | 2022年 / 13卷 / 01期

基金：

澳大利亚研究理事会; 英国医学研究理事会;

关键词：

BARIATRIC SURGERY; UK BIOBANK; ASSOCIATION; METAANALYSIS; OBESITY; HEALTH;

D O I：

10.1038/s41467-022-35553-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：10

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