TY - JOUR
T1 - Multiomics reveal key inflammatory drivers of severe obesity
T2 - IL4R, LILRA5, and OSM
AU - Chen, Hung Hsin
AU - Highland, Heather M.
AU - Frankel, Elizabeth G.
AU - Scartozzi, Alyssa C.
AU - Zhang, Xinruo
AU - Roshani, Rashedeh
AU - Sharma, Priya
AU - Kar, Asha
AU - Buchanan, Victoria L.
AU - Polikowsky, Hannah G.
AU - Petty, Lauren E.
AU - Seo, Jungkyun
AU - Anwar, Mohammad Yaser
AU - Kim, Daeeun
AU - Graff, Mariaelisa
AU - Young, Kristin L.
AU - Zhu, Wanying
AU - Karastergiou, Kalypso
AU - Shaw, Douglas M.
AU - Justice, Anne E.
AU - Fernández-Rhodes, Lindsay
AU - Krishnan, Mohanraj
AU - Gutierrez, Absalon
AU - McCormick, Peter J.
AU - Aguilar-Salinas, Carlos A.
AU - Tusié-Luna, Maria Teresa
AU - Muñoz-Hernandez, Linda Liliana
AU - Herrera-Hernandez, Miguel
AU - Lee, Miryoung
AU - Gamazon, Eric R.
AU - Cox, Nancy J.
AU - Pajukanta, Päivi
AU - Fried, Susan K.
AU - Gordon-Larsen, Penny
AU - Shah, Ravi V.
AU - Fisher-Hoch, Susan P.
AU - McCormick, Joseph B.
AU - North, Kari E.
AU - Below, Jennifer E.
N1 - Publisher Copyright:
© 2025 The Author(s)
PY - 2025/3/12
Y1 - 2025/3/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/86000482483
UR - https://www.scopus.com/pages/publications/86000482483#tab=citedBy
U2 - 10.1016/j.xgen.2025.100784
DO - 10.1016/j.xgen.2025.100784
M3 - Article
C2 - 40043711
AN - SCOPUS:86000482483
SN - 2666-979X
VL - 5
JO - Cell Genomics
JF - Cell Genomics
IS - 3
M1 - 100784
ER -
