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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)84-94
Number of pages11
JournalWorld Journal of Surgery
Volume44
Issue number1
DOIs
StatePublished - Jan 1 2020

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Random Allocation
Body Mass Index
Obesity
Electronic Health Records
Odds Ratio
Genomics
Infection
Logistic Models
Regression Analysis
Intestinal Obstruction
International Classification of Diseases
Single Nucleotide Polymorphism
Retrospective Studies
Incisional Hernia
Genome
Population

ASJC Scopus subject areas

  • Surgery

Cite this

Robinson, J. R., Carroll, R. J., Bastarache, L., Chen, Q., Mou, Z., Wei, W. Q., ... 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

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

In: World Journal of Surgery, Vol. 44, No. 1, 01.01.2020, p. 84-94.

Research output: Contribution to journalArticle

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
Robinson, Jamie R. ; Carroll, Robert J. ; Bastarache, Lisa ; Chen, Qingxia ; Mou, Zongyang ; Wei, Wei Qi ; Connolly, John J. ; Mentch, Frank ; Sleiman, Patrick ; Crane, Paul K. ; Hebbring, Scott J. ; Stanaway, Ian B. ; Crosslin, David R. ; Gordon, Adam S. ; Rosenthal, Elisabeth A. ; Carrell, David ; Hayes, M. Geoffrey ; Wei, Wei ; Petukhova, Lynn ; Namjou, Bahram ; Zhang, Ge ; Safarova, Maya S. ; Walton, Nephi A. ; Still, Christopher ; Bottinger, Erwin P. ; Loos, Ruth J.F. ; Murphy, Shawn N. ; Jackson, Gretchen P. ; Kullo, Iftikhar J. ; Hakonarson, Hakon ; Jarvik, Gail P. ; Larson, Eric B. ; Weng, Chunhua ; Roden, Dan M. ; Denny, Joshua C. / Association of Genetic Risk of Obesity with Postoperative Complications Using Mendelian Randomization. In: World Journal of Surgery. 2020 ; Vol. 44, No. 1. pp. 84-94.
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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.",
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.}",
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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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