Association of Genetic Risk of Obesity with Postoperative Complications Using Mendelian Randomization

The extent to which obesity and genetics determine postoperative complications is incompletely understood.

We performed a retrospective study using two population cohorts with electronic health record (EHR) data. The first included 736,726 adults with body mass index (BMI) recorded between 1990 and 2017 at Vanderbilt University Medical Center. The second cohort consisted of 65,174 individuals from 12 institutions contributing EHR and genome-wide genotyping data to the Electronic Medical Records and Genomics (eMERGE) Network. Pairwise logistic regression analyses were used to measure the association of BMI categories with postoperative complications derived from International Classification of Disease-9 codes, including postoperative infection, incisional hernia, and intestinal obstruction. A genetic risk score was constructed from 97 obesity-risk single-nucleotide polymorphisms for a Mendelian randomization study to determine the association of genetic risk of obesity on postoperative complications. Logistic regression analyses were adjusted for sex, age, site, and race/principal components.

Individuals with overweight or obese BMI (≥25 kg/m²) had increased risk of incisional hernia (odds ratio [OR] 1.7-5.5, p < 3.1 × 10^-20), and people with obesity (BMI ≥ 30 kg/m²) had increased risk of postoperative infection (OR 1.2-2.3, p < 2.5 × 10^-5). In the eMERGE cohort, genetically predicted BMI was associated with incisional hernia (OR 2.1 [95% CI 1.8-2.5], p = 1.4 × 10^-6) and postoperative infection (OR 1.6 [95% CI 1.4-1.9], p = 3.1 × 10^-6). Association findings were similar after limitation of the cohorts to those who underwent abdominal procedures.

Clinical and Mendelian randomization studies suggest that obesity, as measured by BMI, is associated with the development of postoperative incisional hernia and infection.