Genetic architecture of bone marrow fat fraction implies its involvement in osteoporosis risk.

Journal: Nature communications
Published Date: Aug 12, 2025

Abstract

Bone marrow adipose tissue, as a distinct adipose subtype, has been implicated in the pathophysiology of skeletal, metabolic, and hematopoietic disorders. To identify its underlying genetic factors, we utilized a deep learning algorithm capable of quantifying bone marrow fat fraction (BMFF) in the vertebrae and proximal femur using magnetic resonance imaging data of over 38,000 UK Biobank participants. Genome-wide association analyses uncovered 373 significant BMFF-associated variants (P-value < 5 × 10), with enrichment in bone remodeling, metabolism, and hematopoiesis pathway. Furthermore, genetic correlation highlighted a significant association between BMFF and skeletal disease. In about 300,000 individuals, polygenic risk scores derived from three proximal femur BMFF were significantly associated with increased osteoporosis risk. Notably, Mendelian randomization analyses revealed a causal link between proximal femur BMFF and osteoporosis. Here, we show critical insights into the genetic determinants of BMFF and offer perspectives on the biological mechanisms driving osteoporosis development.

Authors

  • Zuyou Wu
    Department of Epidemiology and Biostatistics, School of Public Health, State Key Laboratory of Metabolism and Regulation in Complex Organisms, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, China.
  • Yang Yang
    Department of Gastrointestinal Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, China.
  • Caibo Ning
    Department of Epidemiology and Biostatistics, School of Public Health, State Key Laboratory of Metabolism and Regulation in Complex Organisms, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, China.
  • Jiali Li
    Department of Liver and Pancreatobiliary Surgery, Dongguan People's Hospital, Dongguan, Guangdong, China.
  • Yimin Cai
    Medical College, Guizhou University, Guiyang, 550025, Guizhou, China.
  • Yanmin Li
    Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China.
  • Zilong Cao
    Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China.
  • Shuangshuang Tian
    Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China.
  • Jingyi Peng
    Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China.
  • Qianying Ma
    Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China.
  • Chunyi He
    Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China.
  • Shuting Xia
    Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China.
  • Jun Chen
    Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Xiaoping Miao
    State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment and Health, Ministry of Education, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan, Hubei 430030, China.
  • Zhen Li
    PepsiCo R&D, Valhalla, NY, United States.
  • Ying Zhu
    China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing 100021, China.
  • Qian Chu
    Department of Thoracic Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
  • Jianbo Tian
    Department of Epidemiology and Biostatistics, School of Public Health, State Key Laboratory of Metabolism and Regulation in Complex Organisms, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. tianjb@whu.edu.cn.

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