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

Jamie R. Robinson; 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

doi:10.1007/s00268-019-05202-9

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

Jamie R. Robinson^*, 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 NamjouGe 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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English (US)
Pages (from-to)	84-94
Number of pages	11
Journal	World journal of surgery
Volume	44
Issue number	1
DOIs	https://doi.org/10.1007/s00268-019-05202-9
State	Published - Jan 1 2020

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.

ASJC Scopus subject areas

Surgery

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s00268-019-05202-9

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Robinson, J. R., Carroll, R. J., Bastarache, L., Chen, Q., Mou, Z., Wei, W. Q., Connolly, J. J., Mentch, F., Sleiman, P., Crane, P. K., Hebbring, S. J., Stanaway, I. B., Crosslin, D. R., Gordon, A. S., Rosenthal, E. A., Carrell, D., Hayes, M. G., Wei, W., Petukhova, L., ... Denny, J. C. (2020). Association of Genetic Risk of Obesity with Postoperative Complications Using Mendelian Randomization. World journal of surgery, 44(1), 84-94. https://doi.org/10.1007/s00268-019-05202-9

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title = "Association of Genetic Risk of Obesity with Postoperative Complications Using Mendelian Randomization",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2019, Soci{\'e}t{\'e} Internationale de Chirurgie.",

year = "2020",

month = jan,

day = "1",

doi = "10.1007/s00268-019-05202-9",

language = "English (US)",

volume = "44",

pages = "84--94",

journal = "World journal of surgery",

issn = "0364-2313",

publisher = "John Wiley and Sons Inc.",

number = "1",

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Robinson, JR, Carroll, RJ, Bastarache, L, Chen, Q, Mou, Z, Wei, WQ, Connolly, JJ, Mentch, F, Sleiman, P, Crane, PK, Hebbring, SJ, Stanaway, IB, Crosslin, DR, Gordon, AS, Rosenthal, EA, Carrell, D, Hayes, MG, Wei, W, Petukhova, L, Namjou, B, Zhang, G, Safarova, MS, Walton, NA, Still, C, Bottinger, EP, Loos, RJF, Murphy, SN, Jackson, GP, Kullo, IJ, Hakonarson, H, Jarvik, GP, Larson, EB, Weng, C, Roden, DM & Denny, JC 2020, 'Association of Genetic Risk of Obesity with Postoperative Complications Using Mendelian Randomization', World journal of surgery, vol. 44, no. 1, pp. 84-94. https://doi.org/10.1007/s00268-019-05202-9

TY - JOUR

T1 - Association of Genetic Risk of Obesity with Postoperative Complications Using Mendelian Randomization

AU - Robinson, Jamie R.

AU - Carroll, Robert J.

AU - Bastarache, Lisa

AU - Chen, Qingxia

AU - Mou, Zongyang

AU - Wei, Wei Qi

AU - Connolly, John J.

AU - Mentch, Frank

AU - Sleiman, Patrick

AU - Crane, Paul K.

AU - Hebbring, Scott J.

AU - Stanaway, Ian B.

AU - Crosslin, David R.

AU - Gordon, Adam S.

AU - Rosenthal, Elisabeth A.

AU - Carrell, David

AU - Hayes, M. Geoffrey

AU - Wei, Wei

AU - Petukhova, Lynn

AU - Namjou, Bahram

AU - Zhang, Ge

AU - Safarova, Maya S.

AU - Walton, Nephi A.

AU - Still, Christopher

AU - Bottinger, Erwin P.

AU - Loos, Ruth J.F.

AU - Murphy, Shawn N.

AU - Jackson, Gretchen P.

AU - Kullo, Iftikhar J.

AU - Hakonarson, Hakon

AU - Jarvik, Gail P.

AU - Larson, Eric B.

AU - Weng, Chunhua

AU - Roden, Dan M.

AU - Denny, Joshua C.

PY - 2020/1/1

Y1 - 2020/1/1

N2 - 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.

AB - 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.

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UR - http://www.scopus.com/inward/citedby.url?scp=85074507146&partnerID=8YFLogxK

U2 - 10.1007/s00268-019-05202-9

DO - 10.1007/s00268-019-05202-9

M3 - Article

C2 - 31605180

AN - SCOPUS:85074507146

SN - 0364-2313

VL - 44

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EP - 94

JO - World journal of surgery

JF - World journal of surgery

IS - 1

ER -

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

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