| Title: | Quantifying the phenome-wide disease burden of obesity using electronic health records and genomics |
| Journal: | Obesity |
| Published: | 13 Nov 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/36372681/ |
| DOI: | https://doi.org/10.1002/oby.23561 |
Publication 8071
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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.35 Authors
- 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
- M. Geoffrey Hayes
- Wei Wei
- Lynn Petukhova
- Bahram Namjou-Khales
- Ge Zhang
- Mayya 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
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