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.
JR Robinson received support from the 5T15LM007450 training Grant from the National Library of Medicine. Support for the research and personnel was also provided by the R01LM010685 Grant from the National Library of Medicine. The eMERGE sites were funded through several series of GRANTs from the National Human Genome Research Institute: U01HG8657, U01HG006375, U01HG004610 (Kaiser Permanente Washington/University of Washington); U01HG8685 (Brigham and Women’s Hospital); U01HG8672, U01HG006378, U01HG004608 (Vanderbilt University Medical Center); U01HG8666, U01HG006828 (Cincinnati Children’s Hospital Medical Center); U01HG6379, U01HG04599 (Mayo Clinic); U01HG8679, U01HG006382 (Geisinger Clinic); U01HG008680 (Columbia University Health Sciences); U01HG8684, U01HG006830 (Children’s Hospital of Philadelphia); U01HG8673, U01HG006388, U01HG004609 (Northwestern University); U01HG8676 (Partners Healthcare/Broad Institute); U01HG8664 (Baylor College of Medicine); U01HG006389 (Essentia Institute of Rural Health, Marshfield Clinic Research Foundation and Pennsylvania State University); U01HG006380 (Icahn School of Medicine at Mount Sinai); U01HG8701, U01HG006385, U01HG04603 (Vanderbilt University Medical Center serving as the Coordinating Center); eMERGE Genotyping Centers were also funded through U01HG004438 (CIDR) and U01HG004424 (the Broad Institute). Vanderbilt University Medical Center’s Synthetic Derivative and BioVU are supported by institutional funding and by the CTSA Grant ULTR000445 from NCATS/NIH.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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