학술논문
Quantifying the phenome-wide disease burden of obesity using electronic health records and genomics.
Document Type
article
Author
Mou, Zongyang; Wei, Wei-Qi; Connolly, John; Mentch, Frank; Crane, Paul; Hebbring, Scott; Crosslin, David; Gordon, Adam; Rosenthal, Elisabeth; Stanaway, Ian; Hayes, M; Wei, Wei; Petukhova, Lynn; Namjou-Khales, Bahram; Zhang, Ge; Safarova, Mayya; Walton, Nephi; Still, Christopher; Bottinger, Erwin; Loos, Ruth; Murphy, Shawn; Jackson, Gretchen; Abumrad, Naji; Kullo, Iftikhar; Jarvik, Gail; Larson, Eric; Weng, Chunhua; Roden, Dan; Khera, Amit; Denny, Joshua; Robinson, Jamie; Carroll, Robert; Bastarache, Lisa; Chen, Qingxia; Pirruccello, James
Source
Obesity. 30(12)
Subject
Language
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.