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Cross-Ancestry Comparison of Aptamer and Antibody Proteomics Measures.

Cross-Ancestry Comparison of Aptamer and Antibody Proteomics Measures. Research square Nicholas, J. C., Katz, D. H., Tahir, U. A., Debban, C. L., Aguet, F., Blackwell, T., Bowler, R. P., Broadaway, K. A., Chen, J., Clish, C. B., Coresh, J., Cornell, E., Cruz, D. E., Deo, R., Doyle, M. F., Durda, P., Ekunwe, L., Floyd, J. S., Gill, D., Guo, X., Hoogeveen, R. C., Johnson, C., Lange, L. A., Li, Y., Manning, A., Meigs, J. B., Mi, M. Y., Mychaleckyj, J. C., Olson, N. C., Pratte, K. A., Psaty, B. M., Reiner, A. P., Ruan, P., Sevilla-Gonzalez, M., Shah, A. M., Sun, Q., Tracy, R. P., Wen, J., Wood, A. C., Wilson, J. G., Young, K. L., Yu, B., Rooney, M. R., Manichaikul, A., Dubin, R., Mohlke, K. L., Rich, S. S., Rotter, J. I., Ganz, P., Gerszten, R. E., Taylor, K. D., Raffield, L. M. 2025

Abstract

Measures from affinity-proteomics platforms often correlate poorly, challenging interpretation of protein associations with genetic variants (pQTL) and phenotypes. Here, we examined 2,157 proteins measured on both SomaScan 7k and Olink Explore 3072 across 1,930 participants with genetic similarity to European, African, East Asian, and Admixed American ancestry references. Inter-platform correlation coefficients for these 2,157 proteins followed a bimodal distribution (median r=0.30). Protein measures from each platform were associated with genetic variants (pQTLs), and one-third of the pQTL signals were driven by protein-altering variants (PAVs). We highlight 80 proteins that correlate differently across ancestry groups likely due to differing PAV frequencies by ancestry. Furthermore, adjustment for PAVs with opposite directions of effect by platform improved inter-platform protein measure correlation and resulted in more concordant genetic and phenotypic associations. Hence, PAVs need to be accounted for across ancestries to facilitate platform-concordant and accurate protein measurement.

View details for DOI 10.21203/rs.3.rs-5968391/v1

View details for PubMedID 39989965

View details for PubMedCentralID PMC11844639