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

Austin TR, Fink HA, Jalal DI, Törnqvist AE, Buzkova P, Barzilay JI, Lu T, Carbone L, Gabrielsen ME, Grahnemo L, Hveem K, Jonasson C, Kizer JR, Langhammer A, Mukamal KJ, Gerszten RE, Nethander M, Psaty BM, Robbins JA, Sun YV, Skogholt AH, Åsvold BO, Valderrabano RJ, Zheng J, Richards JB, Coward E, Ohlsson C. Large-scale circulating proteome association study (CPAS) meta-analysis identifies circulating proteins and pathways predicting incident hip fractures. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2024 Jan 4.

Dimensions for VA is a web-based tool available to VA staff that enables detailed searches of published research and research projects.

If you have VA-Intranet access, click here for more information vaww.hsrd.research.va.gov/dimensions/

VA staff not currently on the VA network can access Dimensions by registering for an account using their VA email address.    Search Dimensions for VA for this citation
* Don't have VA-internal network access or a VA email address? Try searching the free-to-the-public version of Dimensions

Search for Abstract from PubMed

---

Abstract:

Hip fractures are associated with significant disability, high cost, and mortality. However, the exact biological mechanisms underlying susceptibility to hip fractures remain incompletely understood. In an exploratory search of the underlying biology as reflected through the circulating proteome, we performed a comprehensive Circulating Proteome Association Study (CPAS) meta-analysis for incident hip fractures. Analyses included 6430 subjects from two prospective cohort studies (Cardiovascular Health Study and Trøndelag Health Study) with circulating proteomics data (aptamer-based 5 K SomaScan version 4.0 assay; 4979 aptamers). Associations between circulating protein levels and incident hip fractures were estimated for each cohort using age and sex-adjusted Cox regression models. Participants experienced 643 incident hip fractures. Compared with the individual studies, inverse-variance weighted meta-analyses yielded more statistically significant associations, identifying 23 aptamers associated with incident hip fractures (conservative Bonferroni correction 0.05/4979, P? < 1.0?×?10-5). The aptamers most strongly associated with hip fracture risk corresponded to two proteins of the growth hormone/insulin growth factor system (GHR and IGFBP2), as well as GDF15 and EGFR. High levels of several inflammation-related proteins (CD14, CXCL12, MMP12, ITIH3) were also associated with increased hip fracture risk. Ingenuity pathway analysis identified reduced LXR/RXR activation and increased acute phase response signaling to be overrepresented among those proteins associated with increased hip fracture risk. These analyses identified several circulating proteins and pathways consistently associated with incident hip fractures. These findings underscore the usefulness of the meta-analytic approach for comprehensive CPAS in a similar manner as has previously been observed for large-scale human genetic studies. Future studies should investigate the underlying biology of these potential novel drug targets.