Genetic architecture of bone marrow fat fraction implies its involvement in osteoporosis risk.
Authors
Affiliations (8)
Affiliations (8)
- 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.
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
- Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China.
- Bayer Healthcare, Wuhan, China.
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. [email protected].
- 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. [email protected].
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. [email protected].
- 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. [email protected].
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<sup>-9</sup>), 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.