상세 보기
- Chen, Hung-Hsin;
- Highland, Heather M.;
- Frankel, Elizabeth G.;
- Scartozzi, Alyssa C.;
- Zhang, Xinruo;
- ... Seo, Jungkyun;
- 외 33명
WEB OF SCIENCE
5SCOPUS
5초록
Polygenic severe obesity (body mass index [BMI] ≥40 kg/m2) has increased, especially in Hispanic/Latino populations, yet we know little about the underlying mechanistic pathways. We analyzed whole-blood multiomics data to identify genes differentially regulated in severe obesity in Mexican Americans from the Cameron County Hispanic Cohort. Our RNA sequencing analysis identified 124 genes significantly differentially expressed between severe obesity cases (BMI ≥40 kg/m2) and controls (BMI <25 kg/m2); 33% replicated in an independent sample from the same population. Our integrative approach identified inflammatory genes, including IL4R, ZNF438, and LILRA5. Several genes displayed transcriptomic effects on severe obesity in subcutaneous adipose tissue. We further showed that the genetic regulation of these genes is associated with several traits in a large biobank, including bone fractures, obstructive sleep apnea, and hyperaldosteronism, illuminating potential risk mechanisms. Our findings furnish a molecular architecture of the severe obesity phenotype across multiple molecular domains. © 2025 The Author(s)
키워드
- 제목
- Multiomics reveal key inflammatory drivers of severe obesity: IL4R, LILRA5, and OSM
- 저자
- Chen, Hung-Hsin; Highland, Heather M.; Frankel, Elizabeth G.; Scartozzi, Alyssa C.; Zhang, Xinruo; Roshani, Rashedeh; Sharma, Priya; Kar, Asha; Buchanan, Victoria L.; Polikowsky, Hannah G.; Petty, Lauren E.; Seo, Jungkyun; Anwar, Mohammad Yaser; Kim, Daeeun; Graff, Mariaelisa; Young, Kristin L.; Zhu, Wanying; Karastergiou, Kalypso; Shaw, Douglas M.; Justice, Anne E.; Fernández-Rhodes, Lindsay; Krishnan, Mohanraj; Gutierrez, Absalon; McCormick, Peter J.; Aguilar-Salinas, Carlos A.; Tusié-Luna, Maria Teresa; Muñoz-Hernandez, Linda Liliana; Herrera-Hernandez, Miguel; Lee, Miryoung; Gamazon, Eric R.; Cox, Nancy J.; Pajukanta, Päivi; Fried, Susan K.; Gordon-Larsen, Penny; Shah, Ravi V.; Fisher-Hoch, Susan P.; McCormick, Joseph B.; North, Kari E.; Below, Jennifer E.
- 발행일
- 2025-03-12
- 유형
- Article
- 저널명
- Cell Genomics
- 권
- 5
- 호
- 3