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

  • Jamie R. RobinsonEmail author
  • Robert J. Carroll
  • Lisa Bastarache
  • Qingxia Chen
  • Zongyang Mou
  • Wei-Qi Wei
  • John J. Connolly
  • Frank Mentch
  • Patrick Sleiman
  • Paul K. Crane
  • Scott J. Hebbring
  • Ian B. Stanaway
  • David R. Crosslin
  • Adam S. Gordon
  • Elisabeth A. Rosenthal
  • David Carrell
  • M. Geoffrey Hayes
  • Wei Wei
  • Lynn Petukhova
  • Bahram Namjou
  • Ge Zhang
  • Maya S. Safarova
  • Nephi A. Walton
  • Christopher Still
  • Erwin P. Bottinger
  • Ruth J. F. Loos
  • Shawn N. Murphy
  • Gretchen P. Jackson
  • Iftikhar J. Kullo
  • Hakon Hakonarson
  • Gail P. Jarvik
  • Eric B. Larson
  • Chunhua Weng
  • Dan M. Roden
  • Joshua C. Denny
Original Scientific Report

Abstract

Background

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

Methods

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.

Results

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.

Conclusions

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

Notes

Funding

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.

Supplementary material

268_2019_5202_MOESM1_ESM.docx (92 kb)
Supplementary material 1 (DOCX 92 kb)
268_2019_5202_MOESM2_ESM.docx (20 kb)
Supplementary material 2 (DOCX 19 kb)

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Copyright information

© Société Internationale de Chirurgie 2019

Authors and Affiliations

  • Jamie R. Robinson
    • 1
    • 2
    Email author
  • Robert J. Carroll
    • 1
  • Lisa Bastarache
    • 1
  • Qingxia Chen
    • 3
  • Zongyang Mou
    • 1
  • Wei-Qi Wei
    • 1
  • John J. Connolly
    • 4
  • Frank Mentch
    • 4
  • Patrick Sleiman
    • 4
  • Paul K. Crane
    • 5
  • Scott J. Hebbring
    • 6
  • Ian B. Stanaway
    • 7
  • David R. Crosslin
    • 7
  • Adam S. Gordon
    • 8
  • Elisabeth A. Rosenthal
    • 8
  • David Carrell
    • 9
  • M. Geoffrey Hayes
    • 10
  • Wei Wei
    • 11
  • Lynn Petukhova
    • 12
  • Bahram Namjou
    • 13
  • Ge Zhang
    • 14
    • 15
  • Maya S. Safarova
    • 16
  • Nephi A. Walton
    • 17
  • Christopher Still
    • 17
  • Erwin P. Bottinger
    • 18
  • Ruth J. F. Loos
    • 18
  • Shawn N. Murphy
    • 19
  • Gretchen P. Jackson
    • 1
    • 20
  • Iftikhar J. Kullo
    • 16
  • Hakon Hakonarson
    • 4
  • Gail P. Jarvik
    • 8
  • Eric B. Larson
    • 9
  • Chunhua Weng
    • 21
  • Dan M. Roden
    • 1
    • 22
    • 23
  • Joshua C. Denny
    • 1
    • 22
  1. 1.Department of Biomedical InformaticsVanderbilt University Medical CenterNashvilleUSA
  2. 2.Department of SurgeryVanderbilt University Medical CenterNashvilleUSA
  3. 3.Department of BiostatisticsVanderbilt University Medical CenterNashvilleUSA
  4. 4.The Center for Applied GenomicsThe Children’s Hospital of PhiladelphiaPhiladelphiaUSA
  5. 5.Department of MedicineUniversity of WashingtonSeattleUSA
  6. 6.Center for Human GeneticsMarshfield Clinic Research InstituteMarshfieldUSA
  7. 7.Department of Biomedical Informatics and Medical EducationUniversity of WashingtonSeattleUSA
  8. 8.Division of Medical Genetics, Department of MedicineUniversity of WashingtonSeattleUSA
  9. 9.Kaiser Permanente Washington Health Research InstituteSeattleUSA
  10. 10.Division of Endocrinology, Metabolism, and Molecular Medicine, Department of MedicineNorthwestern University Feinberg School of MedicineChicagoUSA
  11. 11.University of Pittsburgh Medical CenterPittsburghUSA
  12. 12.Departments of Dermatology and EpidemiologyColumbia UniversityNew YorkUSA
  13. 13.Center for Autoimmune Genomics and EtiologyCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  14. 14.Division of Human Genetics, Cincinnati Children’s Hospital Medical CenterUniversity of Cincinnati College of MedicineCincinnatiUSA
  15. 15.Department of PediatricsUniversity of Cincinnati College of MedicineCincinnatiUSA
  16. 16.Department of Cardiovascular DiseasesMayo ClinicRochesterUSA
  17. 17.Department of Biomedical and Translational InformaticsGeisinger Health SystemDanvilleUSA
  18. 18.The Charles Bronfman Institute for Personalized Medicine at Mount SinaiThe Mindich Child Health and Development InstituteNew YorkUSA
  19. 19.Department of NeurologyPartners HealthcareBostonUSA
  20. 20.Department of Pediatric SurgeryVanderbilt University Medical CenterNashvilleUSA
  21. 21.Department of Biomedical InformaticsColumbia UniversityNew YorkUSA
  22. 22.Department of MedicineVanderbilt University Medical CenterNashvilleUSA
  23. 23.Department of PharmacologyVanderbilt University Medical CenterNashvilleUSA

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