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

Cardiovascular Medicine

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

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

ASJC Scopus subject areas

Surgery

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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

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

@article{8fff7834e3ee49539ea516ad51ee2af7,

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 = "Springer New York",

number = "1",

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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

SP - 84

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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