Large-scale circulating proteome association study (CPAS) meta-analysis identifies circulating proteins and pathways...

Area of Science:

• Biochemistry
• Genetics
• Epidemiology

Background:

• Hip fractures cause significant disability, mortality, and healthcare costs.
• The biological mechanisms predisposing individuals to hip fractures are not fully understood.

Purpose of the Study:

• To explore the biological underpinnings of hip fracture susceptibility using a comprehensive Circulating Proteome Association Study (CPAS) meta-analysis.
• To identify circulating proteins and biological pathways associated with incident hip fractures.

Main Methods:

• A meta-analysis of two prospective cohort studies (Cardiovascular Health Study and Trøndelag Health Study) involving 6430 participants.
• Circulating proteomics data analyzed using aptamer-based assays (4979 aptamers).
• Cox regression models and inverse-variance weighted meta-analyses were employed to assess associations between protein levels and hip fractures.

Main Results:

• Identified 23 aptamers significantly associated with incident hip fractures.
• Strongest associations were with proteins in the growth hormone/insulin growth factor system (GHR, IGFBP2), GDF15, and EGFR.
• Elevated levels of inflammation-related proteins (CD14, CXCL12, MMP12, ITIH3) were linked to increased hip fracture risk.

Conclusions:

• The meta-analytic CPAS approach effectively identified circulating proteins and pathways associated with hip fractures.
• Findings suggest novel drug targets for hip fracture prevention, particularly related to growth hormone signaling and inflammation.
• Further research is warranted to elucidate the biological roles of these identified proteins in hip fracture pathogenesis.