Quantifying the phenome-wide disease burden of obesity using electronic health records and genomics

Jamie R. Robinson*, Robert J. Carroll, Lisa Bastarache, Qingxia Chen, James Pirruccello, Zongyang Mou, Wei Qi Wei, John Connolly, Frank Mentch, Paul K. Crane, Scott J. Hebbring, David R. Crosslin, Adam S. Gordon, Elisabeth A. Rosenthal, Ian B. Stanaway, Michael Geoffrey Hayes, Wei Wei, Lynn Petukhova, Bahram Namjou-Khales, Ge ZhangMayya S. Safarova, Nephi A. Walton, Christopher Still, Erwin P. Bottinger, Ruth J.F. Loos, Shawn N. Murphy, Gretchen P. Jackson, Naji Abumrad, Iftikhar J. Kullo, Gail P. Jarvik, Eric B. Larson, Chunhua Weng, Dan Roden, Amit V. Khera, Joshua C. Denny

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: High BMI is associated with many comorbidities and mortality. This study aimed to elucidate the overall clinical risk of obesity using a genome- and phenome-wide approach. Methods: This study performed a phenome-wide association study of BMI using a clinical cohort of 736,726 adults. This was followed by genetic association studies using two separate cohorts: one consisting of 65,174 adults in the Electronic Medical Records and Genomics (eMERGE) Network and another with 405,432 participants in the UK Biobank. Results: Class 3 obesity was associated with 433 phenotypes, representing 59.3% of all billing codes in individuals with severe obesity. A genome-wide polygenic risk score for BMI, accounting for 7.5% of variance in BMI, was associated with 296 clinical diseases, including strong associations with type 2 diabetes, sleep apnea, hypertension, and chronic liver disease. In all three cohorts, 199 phenotypes were associated with class 3 obesity and polygenic risk for obesity, including novel associations such as increased risk of renal failure, venous insufficiency, and gastroesophageal reflux. Conclusions: This combined genomic and phenomic systematic approach demonstrated that obesity has a strong genetic predisposition and is associated with a considerable burden of disease across all disease classes.

Original languageEnglish (US)
Pages (from-to)2477-2488
Number of pages12
JournalObesity
Volume30
Issue number12
DOIs
StatePublished - Dec 2022

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Nutrition and Dietetics

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