Quantifying the phenome-wide disease burden of obesity using electronic health records and genomics
Robinson, Jamie R; Carroll, Robert J; Bastarache, Lisa; Chen, Qingxia; Pirruccello, James; Mou, Zongyang; Wei, Wei-Qi; Connolly, John; Mentch, Frank; Crane, Paul K; Hebbring, Scott J; Crosslin, David R; Gordon, Adam S; Rosenthal, Elisabeth A; Stanaway, Ian B; Hayes, M Geoffrey; Wei, Wei; Petukhova, Lynn; Namjou-Khales, Bahram; Zhang, Ge; Safarova, Mayya S; Walton, Nephi A; Still, Christopher; Bottinger, Erwin P; Loos, Ruth J F; Murphy, Shawn N; Jackson, Gretchen P; Abumrad, Naji; Kullo, Iftikhar J; Jarvik, Gail P; Larson, Eric B; Weng, Chunhua; Roden, Dan; Khera, Amit V; Denny, Joshua C
OBJECTIVE:High BMI is associated with many comorbidities and mortality. This study aimed to elucidate the overall clinical risk of obesity using a genome- and phenome-wide approach. METHODS:This study performed a phenome-wide association study of BMI using a clinical cohort of 736,726 adults. This was followed by genetic association studies using two separate cohorts: one consisting of 65,174 adults in the Electronic Medical Records and Genomics (eMERGE) Network and another with 405,432 participants in the UK Biobank. RESULTS:Class 3 obesity was associated with 433 phenotypes, representing 59.3% of all billing codes in individuals with severe obesity. A genome-wide polygenic risk score for BMI, accounting for 7.5% of variance in BMI, was associated with 296 clinical diseases, including strong associations with type 2 diabetes, sleep apnea, hypertension, and chronic liver disease. In all three cohorts, 199 phenotypes were associated with class 3 obesity and polygenic risk for obesity, including novel associations such as increased risk of renal failure, venous insufficiency, and gastroesophageal reflux. CONCLUSIONS:This combined genomic and phenomic systematic approach demonstrated that obesity has a strong genetic predisposition and is associated with a considerable burden of disease across all disease classes.
PMCID:9691570
PMID: 36372681
ISSN: 1930-739x
CID: 5710602
Neptune: an environment for the delivery of genomic medicine
Eric, Venner; Yi, Victoria; Murdock, David; Kalla, Sara E; Wu, Tsung-Jung; Sabo, Aniko; Li, Shoudong; Meng, Qingchang; Tian, Xia; Murugan, Mullai; Cohen, Michelle; Kovar, Christie; Wei, Wei-Qi; Chung, Wendy K; Weng, Chunhua; Wiesner, Georgia L; Jarvik, Gail P; Muzny, Donna; Gibbs, Richard A; Abrams, Debra; Adunyah, Samuel E; Albertson-Junkans, Ladia; Almoguera, Berta; 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; 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 R; Dayal, Jyoti; De Andrade, Mariza; De la Cruz, Jessica; Denny, Josh C; Denson, Shawn; DeSmet, Tim; Dikilitas, Ozan; Dinsmore, Michael J; Dodge, Sheila; Dunlea, Phil; Edwards, Todd L; Eng, Christine M; Fasel, David; Fedotov, Alex; Feng, Qiping; Fleharty, Mark; Foster, Andrea; Freimuth, Robert; Friedrich, Christopher; Fullerton, Stephanie M; Funke, Birgit; Gabriel, Stacey; Gainer, Vivian; Gharavi, Ali; Gibbs, Richard A; Glazer, Andrew M; Glessner, Joseph T; Goehringer, Jessica; Gordon, Adam S; Graham, Chet; Green, Robert C; Gundelach, Justin H; 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; Hynes, Elizabeth Duffy; Jarvik, Gail P; Jayaseelan, Joy C; Jiang, Yunyun; Joo, Yoonjung Yoonie; Jose, Sheethal; Josyula, Navya Shilpa; Justice, Anne E; Kalra, Divya; Karlson, Elizabeth W; Keating, Brendan J; Kelly, Melissa A; Kenny, Eimear E; Key, Dustin; Kiryluk, Krzysztof; Kitchner, Terrie; Klanderman, Barbara; Klee, Eric; Kochan, David C; Korchina, Viktoriya; Kottyan, Leah; Kudalkar, Emily; Rahm, Alanna Kulchak; Kullo, Iftikhar J; Lammers, Philip; Larson, Eric B; Lebo, Matthew S; Leduc, Magalie; Lee, Ming Ta Michael; Lennon, Niall J; Leppig, Kathleen A; Leslie, Nancy D; Li, Rongling; Liang, Wayne H; Lin, Chiao-Feng; Linder, Jodell E; 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, Bradley; Manolio, Teri; Marasa, Maddalena; Marsolo, Keith; McGowan, Michelle L; McNally, Elizabeth; Meldrim, Jim; Mentch, Frank; Rasouly, Hila Milo; Mosley, Jonathan; Mukherjee, Shubhabrata; Mullen, Thomas E; Muniz, Jesse; Murdock, David R; Murphy, Shawn; Murugan, Mullai; Muzny, Donna; Myers, Melanie F; Namjou, Bahram; Ni, Yizhao; Onofrio, Robert C; Obeng, Aniwaa Owusu; Person, Thomas N; Peterson, Josh F; Petukhova, Lynn; Pisieczko, Cassandra J; Pratap, Siddharth; Prows, Cynthia A; Puckelwartz, Megan J; Raj, Ritika; Ralston, James D; Ramaprasan, Arvind; Ramirez, Andrea; Rasmussen, Luke; Rasmussen-Torvik, Laura; Raychaudhuri, Soumya; Rehm, Heidi L; Ritchie, Marylyn D; Rives, Catherine; Riza, Beenish; Roden, Dan M; Rosenthal, Elisabeth A; Santani, Avni; Dan, Schaid; 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; Smoot, Duane T; Smoller, Jordan W; Sohn, Sunghwan; Stanaway, Ian B; Starren, Justin; Stroud, Mary; Su, Jessica; Taylor, Casey Overby; Tolwinski, Kasia; Van Driest, Sara L; Vargas, Sean M; Varugheese, Matthew; Veenstra, David; Venner, Eric; Verbitsky, Miguel; Vicente, Gina; Wagner, Michael; Walker, Kimberly; Walunas, Theresa; Wang, Liwen; Wang, Qiaoyan; Wei, Wei-Qi; Weiss, Scott T; Wells, Quinn S; Weng, Chunhua; White, Peter S; Wiesner, Georgia L; Wiley, Ken L Jr; Williams, Janet L; Williams, Marc S; Wilson, Michael W; Witkowski, Leora; Woods, Laura Allison; Woolf, Betty; Wynn, Julia; Yang, Yaping; Zhang, Ge; Zhang, Lan; Zouk, Hana
PURPOSE:Genomic medicine holds great promise for improving health care, but integrating searchable and actionable genetic data into electronic health records (EHRs) remains a challenge. Here we describe Neptune, a system for managing the interaction between a clinical laboratory and an EHR system during the clinical reporting process. METHODS:We developed Neptune and applied it to two clinical sequencing projects that required report customization, variant reanalysis, and EHR integration. RESULTS:Neptune has been applied for the generation and delivery of over 15,000 clinical genomic reports. This work spans two clinical tests based on targeted gene panels that contain 68 and 153 genes respectively. These projects demanded customizable clinical reports that contained a variety of genetic data types including single-nucleotide variants (SNVs), copy-number variants (CNVs), pharmacogenomics, and polygenic risk scores. Two variant reanalysis activities were also supported, highlighting this important workflow. CONCLUSION:Methods are needed for delivering structured genetic data to EHRs. This need extends beyond developing data formats to providing infrastructure that manages the reporting process itself. Neptune was successfully applied on two high-throughput clinical sequencing projects to build and deliver clinical reports to EHR systems. The software is open source and available at https://gitlab.com/bcm-hgsc/neptune .
PMCID:8487966
PMID: 34257418
ISSN: 1530-0366
CID: 5479332