Gulisija Davorka, Gonzalez-Reymundez Agustin, Fenton Jenifer I, de Los Campos Gustavo, Bray Molly S, Vazquez Ana I
Department of Biology, University of New Mexico, Albuquerque, New Mexico, USA.
Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, Michigan, USA.
Obesity (Silver Spring). 2025 Jun;33(6):1184-1194. doi: 10.1002/oby.24291. Epub 2025 May 26.
Effective solutions to obesity remain elusive, partly owing to its root in a positive energy balance (EB), which stems from the interplay of numerous traits spanning body size and composition, diet, physical activity, and metabolic profile. Nevertheless, EB-contributing traits are typically studied in isolation. We integrate numerous EB-related traits measured in the UK Biobank to uncover the underlying patterns of EB and associated genes in study participants.
We used sparse factor analysis to integrate traits and performed genome-wide association analyses on the integrated phenotypes to elucidate EB-related genes and metabolic pathways. We performed pleiotropy analyses on candidate single-nucleotide polymorphisms to uncover the genetic basis of EB.
We identified multiple genes and genomic regions associated with EB, including many that have previously not been directly associated with obesity measures (e.g., MIR5591, FNDC3B, ANAPC10, SULT1A1, AXIN1, SKIDA1, ERLIN1, DOCK7), which we validated using an independent subset of the UK Biobank dataset along with data from the Atherosclerosis Risk in Communities cohort. We found that the covariances in EB traits are primarily driven by genome-wide pleiotropic associations.
We offer new insight into EB patterns and the genetic basis of EB.
肥胖的有效解决方案仍然难以捉摸，部分原因在于其根源是正能量平衡（EB），这源于众多特征之间的相互作用，这些特征涵盖身体大小和组成、饮食、身体活动以及代谢特征。然而，通常孤立地研究对正能量平衡有贡献的特征。我们整合了英国生物银行中测量的众多与正能量平衡相关的特征，以揭示研究参与者中正能量平衡的潜在模式和相关基因。
我们使用稀疏因子分析来整合特征，并对整合后的表型进行全基因组关联分析，以阐明与正能量平衡相关的基因和代谢途径。我们对候选单核苷酸多态性进行多效性分析，以揭示正能量平衡的遗传基础。
我们鉴定出多个与正能量平衡相关的基因和基因组区域，包括许多以前未直接与肥胖测量相关的基因（例如，MIR5591、FNDC3B、ANAPC10、SULT1A1、AXIN1、SKIDA1、ERLIN1、DOCK7），我们使用英国生物银行数据集的一个独立子集以及社区动脉粥样硬化风险队列的数据对其进行了验证。我们发现正能量平衡特征中的协方差主要由全基因组多效性关联驱动。
我们为正能量平衡模式及其遗传基础提供了新的见解。
