期刊
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
卷 107, 期 5, 页码 E2133-E2140出版社
ENDOCRINE SOC
DOI: 10.1210/clinem/dgab911
关键词
Mendelian randomization; body composition; plasma proteome; causal relationship
资金
- National Natural Science Foundation of China [32170670, 31771417]
- Priority Academic Program Development (PAPD) of Jiangsu higher education institutions
- Suzhou Science and Technology Bureau [SKY2021022]
- Gusu Health Top-Notch Youth Talent of Suzhou Health Commission [GSWS2019086]
- Wujiang District Health Commission [WWK201806]
This study utilized Mendelian randomization analysis to evaluate the causal relationship between plasma proteins and body composition, finding evidence of causal relationships and providing a basis for further studies.
Context Observational studies have demonstrated associations between plasma proteins and obesity, but evidence of causal relationship remains to be studied. Objective We aimed to evaluate the causal relationship between plasma proteins and body composition. Methods We conducted a 2-sample Mendelian randomization (MR) analysis based on the genome-wide association study (GWAS) summary statistics of 23 body composition traits and 2656 plasma proteins. We then performed hierarchical cluster analysis to evaluate the structure and pattern of the identified causal associations, and we performed gene ontology enrichment analysis to explore the functional relevance of the identified proteins. Results We identified 430 putatively causal effects of 96 plasma proteins on 22 body composition traits (except obesity status) with strong MR evidence (P < 2.53 x 10( - 6), at a Bonferroni-corrected threshold). The top 3 causal associations are follistatin (FST) on trunk fat-free mass (Beta = -0.63, SE = 0.04, P = 2.00 x 10(-63)), insulin-like growth factor-binding protein 1 (IGFBP1) on trunk fat-free mass (Beta = -0.54, SE = 0.03, P = 1.79 x 10(-57)) and r-spondin-3 (RSPO3) on WHR (waist circumference/hip circumference) (Beta = 0.01, SE = 4.47 x 10(-4), P = 5.45 x 10(-60)), respectively. Further clustering analysis and pathway analysis demonstrated that the pattern of causal effect to fat mass and fat-free mass may be different. Conclusion Our findings may provide evidence for causal relationships from plasma proteins to various body composition traits and provide basis for further targeted functional studies.
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