J Clin Endocrinol Metab. 2021 Dec 18:dgab911. doi: 10.1210/clinem/dgab911. Online ahead of print.
ABSTRACT
BACKGROUND: Observational studies have demonstrated associations between plasma proteins and obesity, but evidence of causal relationship remains to be studied.
METHODS: To evaluate the causal relationship between plasma proteins and body composition, we conducted a two-sample Mendelian randomization (MR) analysis based on the genome-wide association study (GWAS) summary statistics of 23 body composition traits and 2,656 plasma proteins. We then performed hierarchical cluster analysis to evaluate the structure and pattern of the identified causal associations, and 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 × 10 -6, at a Bonferroni-corrected threshold). The top 3 causal associations are FST (follistatin) on trunk fat-free mass (Beta = -0.63, SE = 0.04, P = 2.00 × 10 -63), IGFBP1 (insulin-like growth factor-binding protein 1) on trunk fat-free mass (Beta = -0.54, SE = 0.03, P = 1.79 × 10 -57) and RSPO3 (r-spondin-3) on WHR (waist circumference/hip circumference) (Beta = 0.01, SE= 4.47 × 10 -4, P = 5.45 × 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.
PMID:34922401 | DOI:10.1210/clinem/dgab911
