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
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:). 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.
PMID: 31605180
ISSN: 1432-2323
CID: 5710532
Harmonizing Clinical Sequencing and Interpretation for the eMERGE III Network
[Zouk, Hana; Venner, Eric; Lennon, Niall J; Muzny, Donna M; Abrams, Debra; Adunyah, Samuel; Albertson-Junkans, Ladia; Ames, Darren C; Appelbaum, Paul; Aronson, Samuel; Aufox, Sharon; Babb, Lawrence J; Balasubramanian, Adithya; Bangash, Hana; Basford, Melissa; Bastarache, Lisa; Baxter, Samantha; Behr, Meckenzie; Benoit, Barbara; Bhoj, Elizabeth; Bielinski, Suzette J; Bland, Sarah T; Blout, Carrie; Borthwick, Kenneth; Bottinger, Erwin P; Bowser, Mark; Brand, Harrison; Brilliant, Murray; Brodeur, Wendy; Caraballo, Pedro; Carrell, David; Carroll, Andrew; Almoguera, Berta; Castillo, Lisa; Castro, Victor; Chandanavelli, Gauthami; Chiang, Theodore; Chisholm, Rex L; Christensen, Kurt D; Chung, Wendy; Chute, Christopher G; City, Brittany; Cobb, Beth L; Connolly, John J; Crane, Paul; Crew, Katherine; Crosslin, David; De Andrade, Mariza; De la Cruz, Jessica; Denson, Shawn; Denny, Josh; DeSmet, Tim; Dikilitas, Ozan; Friedrich, Christopher; Fullerton, Stephanie M; Funke, Birgit; Gabriel, Stacey; Gainer, Vivian; Gharavi, Ali; Glazer, Andrew M; Glessner, Joseph T; Goehringer, Jessica; Gordon, Adam S; Graham, Chet; Green, Robert C; Gundelach, Justin H; Dayal, Jyoti; Hain, Heather S; Hakonarson, Hakon; Harden, Maegan V; Harley, John; Harr, Margaret; Hartzler, Andrea; Hayes, M Geoffrey; Hebbring, Scott; Henrikson, Nora; Hershey, Andrew; Hoell, Christin; Holm, Ingrid; Howell, Kayla M; Hripcsak, George; Hu, Jianhong; Jarvik, Gail P; Jayaseelan, Joy C; Jiang, Yunyun; Joo, Yoonjung Yoonie; Jose, Sheethal; Josyula, Navya Shilpa; Justice, Anne E; Kalla, Sara E; Kalra, Divya; Karlson, Elizabeth; Kelly, Melissa A; Keating, Brendan J; Kenny, Eimear E; Key, Dustin; Kiryluk, Krzysztof; Kitchner, Terrie; Klanderman, Barbara; Klee, Eric; Kochan, David C; Korchina, Viktoriya; Kottyan, Leah; Kovar, Christie; Kudalkar, Emily; Kullo, Iftikhar J; Lammers, Philip; Larson, Eric B; Lebo, Matthew S; Leduc, Magalie; Lee, Ming Ta Michael; Leppig, Kathleen A; Leslie, Nancy D; Li, Rongling; Liang, Wayne H; Lin, Chiao-Feng; Linder, Jodell; Lindor, Noralane M; Lingren, Todd; Linneman, James G; Liu, Cong; Liu, Wen; Liu, Xiuping; Lynch, John; Lyon, Hayley; Macbeth, Alyssa; Mahadeshwar, Harshad; Mahanta, Lisa; Malin, Brad; Manolio, Teri; Marasa, Maddalena; Marsolo, Keith; Dinsmore, Michael J; Dodge, Sheila; Hynes, Elizabeth Duffy; Dunlea, Phil; Edwards, Todd L; Eng, Christine M; Fasel, David; Fedotov, Alex; Feng, Qiping; Fleharty, Mark; Foster, Andrea; Freimuth, Robert; McGowan, Michelle L; McNally, Elizabeth; Meldrim, Jim; Mentch, Frank; Mosley, Jonathan; Mukherjee, Shubhabrata; Mullen, Thomas E; Muniz, Jesse; Murdock, David R; Murphy, Shawn; Murugan, Mullai; Myers, Melanie F; Namjou, Bahram; Ni, Yizhao; Obeng, Aniwaa Owusu; Onofrio, Robert C; Taylor, Casey Overby; Person, Thomas N; Peterson, Josh F; Petukhova, Lynn; Pisieczko, Cassandra J; Pratap, Siddharth; Prows, Cynthia A; Puckelwartz, Megan J; Rahm, Alanna Kulchak; Raj, Ritika; Ralston, James D; Ramaprasan, Arvind; Ramirez, Andrea; Rasmussen, Luke; Rasmussen-Torvik, Laura; Rasouly, Hila Milo; Raychaudhuri, Soumya; Ritchie, Marylyn D; Rives, Catherine; Riza, Beenish; Roden, Dan; Rosenthal, Elisabeth A; Santani, Avni; Schaid, Dan; Scherer, Steven; Scott, Stuart; Scrol, Aaron; Sengupta, Soumitra; Shang, Ning; Sharma, Himanshu; Sharp, Richard R; Singh, Rajbir; Sleiman, Patrick M A; Slowik, Kara; Smith, Joshua C; Smith, Maureen E; Smoller, Jordan W; Sohn, Sunghwan; Stanaway, Ian B; Starren, Justin; Stroud, Mary; Su, Jessica; Tolwinski, Kasia; Van Driest, Sara L; Vargas, Sean M; Varugheese, Matthew; Veenstra, David; Verbitsky, Miguel; Vicente, Gina; Wagner, Michael; Walker, Kimberly; Walunas, Theresa; Wang, Liwen; Wang, Qiaoyan; Wei, Wei-Qi; Weiss, Scott T; Wiesner, Georgia L; Wells, Quinn; Weng, Chunhua; White, Peter S; Wiley, Ken L Jr; Williams, Janet L; Williams, Marc S; Wilson, Michael W; Witkowski, Leora; Woods, Laura Allison; Woolf, Betty; Wu, Tsung-Jung; Wynn, Julia; Yang, Yaping; Yi, Victoria; Zhang, Ge; Zhang, Lan; Rehm, Heidi L; Gibbs, Richard A]
The advancement of precision medicine requires new methods to coordinate and deliver genetic data from heterogeneous sources to physicians and patients. The eMERGE III Network enrolled >25,000 participants from biobank and prospective cohorts of predominantly healthy individuals for clinical genetic testing to determine clinically actionable findings. The network developed protocols linking together the 11 participant collection sites and 2 clinical genetic testing laboratories. DNA capture panels targeting 109 genes were used for testing of DNA and sample collection, data generation, interpretation, reporting, delivery, and storage were each harmonized. A compliant and secure network enabled ongoing review and reconciliation of clinical interpretations, while maintaining communication and data sharing between clinicians and investigators. A total of 202 individuals had positive diagnostic findings relevant to the indication for testing and 1,294 had additional/secondary findings of medical significance deemed to be returnable, establishing data return rates for other testing endeavors. This study accomplished integration of structured genomic results into multiple electronic health record (EHR) systems, setting the stage for clinical decision support to enable genomic medicine. Further, the established processes enable different sequencing sites to harmonize technical and interpretive aspects of sequencing tests, a critical achievement toward global standardization of genomic testing. The eMERGE protocols and tools are available for widespread dissemination.
PMCID:6731372
PMID: 31447099
ISSN: 1537-6605
CID: 5479312
Specimen Collection for Translational Studies in Hidradenitis Suppurativa
Byrd, A S; Dina, Y; Okoh, U J; Quartey, Q Q; Carmona-Rivera, C; Williams, D W; Kerns, M L; Miller, R J; Petukhova, L; Naik, H B; Barnes, L A; Shipman, W D; Caffrey, J A; Sacks, J M; Milner, S M; Aliu, O; Broderick, K P; Kim, D; Liu, H; Dillen, C A; Ahn, R; Frew, J W; Kaplan, M J; Kang, S; Garza, L A; Miller, L S; Alavi, A; Lowes, M A; Okoye, G A
Hidradenitis suppurativa (HS) is a chronic inflammatory disorder characterized by painful nodules, sinus tracts, and scars occurring predominantly in intertriginous regions. The prevalence of HS is currently 0.053-4%, with a predominance in African-American women and has been linked to low socioeconomic status. The majority of the reported literature is retrospective, population based, epidemiologic studies. In this regard, there is a need to establish a repository of biospecimens, which represent appropriate gender and racial demographics amongst HS patients. These efforts will diminish knowledge gaps in understanding the disease pathophysiology. Hence, we sought to outline a step-by-step protocol detailing how we established our HS biobank to facilitate the formation of other HS tissue banks. Equipping researchers with carefully detailed processes for collection of HS specimens would accelerate the accumulation of well-organized human biological material. Over time, the scientific community will have access to a broad range of HS tissue biospecimens, ultimately leading to more rigorous basic and translational research. Moreover, an improved understanding of the pathophysiology is necessary for the discovery of novel therapies for this debilitating disease. We aim to provide high impact translational research methodology for cutaneous biology research and foster multidisciplinary collaboration and advancement of our understanding of cutaneous diseases.
PMCID:6704132
PMID: 31434914
ISSN: 2045-2322
CID: 5710782