Ying Yuchen, Zhang Chunxia, Wu Shanshan, Wang Shudan, Lian Jiangfang, Lin Yupin, Guan Haiwang, Cai Dihui
Department of cardiology, Ningbo Medical Center of Lihuili Hospital, Ningbo, China.
Cardiac Care Unit, Ningbo Medical Center of Lihuili Hospital, Ningbo, China.
Cardiorenal Med. 2025;15(1):295-308. doi: 10.1159/000545641. Epub 2025 Apr 3.
Fat-free mass (FFM) is a critical component of the human body, with implications for various diseases.
We conducted a comprehensive analysis integrating a phenome-wide association study (PheWAS), a two-sample Mendelian randomization (MR) analysis, and a systematic review to investigate the associations between FFM and health outcomes.
PheWAS identified 183 phenotypes enriched for FFM associations, including diseases, body composition, and lifestyle factors. A two-sample MR analysis using the FinnGen and UK Biobank dataset revealed significant associations between genetically determined FFM and 36 disease outcomes, including cardiovascular diseases, metabolic disorders, and musculoskeletal conditions. The mediation MR analysis indicates that FFM indirectly influences the levels of five biomarkers in visceral adipose tissue. A systematic review identified consistent associations between FFM and several diseases, including type 2 diabetes and cervical disc disorders. Moreover, new associations such as low back pain and ovarian cancer were discovered.
These findings challenge the conventional notion of FFM as a protective factor in health, suggesting that higher FFM levels may be linked to an increased risk of various diseases. Further clinical studies are warranted to validate these findings and elucidate the underlying mechanisms.
去脂体重（FFM）是人体的一个关键组成部分，与多种疾病相关。
我们进行了一项综合分析，整合了全表型关联研究（PheWAS）、两样本孟德尔随机化（MR）分析和系统评价，以研究FFM与健康结局之间的关联。
PheWAS确定了183种因FFM关联而富集的表型，包括疾病、身体组成和生活方式因素。使用芬兰基因库（FinnGen）和英国生物银行（UK Biobank）数据集进行的两样本MR分析显示，基因决定的FFM与36种疾病结局之间存在显著关联，包括心血管疾病、代谢紊乱和肌肉骨骼疾病。中介MR分析表明，FFM间接影响内脏脂肪组织中五种生物标志物的水平。系统评价确定了FFM与几种疾病之间存在一致关联，包括2型糖尿病和颈椎间盘疾病。此外，还发现了如腰痛和卵巢癌等新的关联。
这些发现挑战了FFM是健康保护因素的传统观念，表明较高的FFM水平可能与多种疾病风险增加有关。需要进一步的临床研究来验证这些发现并阐明潜在机制。
