Cross-ancestry comparison of aptamer and antibody protein measures

Authors: NICHOLAS, JAYNA - University Of North Carolina; KATZ, DANIEL - Stanford University; TAHIR, USMAN - Beth Israel Deaconess Medical Center; DEBBAN, CATHERINE - University Of Virginia; AGUET, FRANCOIS - Broad Institute Of Mit/harvard; BLACKWELL, THOMAS - University Of Michigan; BOWLER, RUSSELL - Cleveland Clinic; BROADAWAY, K - University Of North Carolina; CHEN, JINGSHA - Johns Hopkins School Of Public Health; CLISH, CLARY - Broad Institute Of Mit/harvard; CORESH, JOSEF - New York University; CORNELL, ELAINE - University Of Vermont; CRUZ, DANIEL - Beth Israel Deaconess Medical Center; DEO, RAJAT - University Of Pennsylvania; DOYLE, MARGARET - University Of Vermont; DURDA, PETER - University Of Vermont; EKUNWE, LYNETTE - University Of Mississippi Medical Center; FLOYD, JAMES - University Of Washington School Of Medicine; GILL, DIPENDER - Non ARS Employee; GUO, XIUQING - Harbor-Ucla Medical Center; HOOGEVEEN, RON - Baylor College Of Medicine; JOHNSON, CRAIG - University Of Washington; LANGE, LESLIE - University Of Colorado; LI, YUN - University Of North Carolina; MANNING, ALISA - Broad Institute Of Mit/harvard; MEIGS, JAMES - Broad Institute Of Mit/harvard; MI, MICHAEL - Beth Israel Deaconess Medical Center; MYCHALECKYJ, JOSYF - University Of Virginia; OLSON, NELS - University Of Vermont; PRATTE, KATHERINE - National Jewish Health; PSATY, BRUCY - University Of Washington; REINER, ALEXANDER - Fred Hutchinson Cancer Research Center; RUAN, PEIFENG - University Of Texas Southwestern Medical Center; SEVILLA-GONZALEZ, MAGDALENA - Massachusetts General Hospital; SHAH, AMIL - University Of Texas Southwestern Medical Center; SUN, QUAN - University Of North Carolina; TRACY, RUSSELL - University Of Vermont; WEN, JIA - University Of North Carolina; WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC); WILSON, JAMES - Beth Israel Deaconess Medical Center; YOUNG, KRISTIN - University Of North Carolina; YU, BING - Uthealth Houston School Of Public Health; ROONEY, MARY - Johns Hopkins School Of Public Health; MANICHAIKUL, ANI - University Of Virginia; DUBIN, RUTH - University Of Texas Southwestern Medical Center; MOHLKE, KAREN - University Of North Carolina; RICH, STEPHEN - University Of Virginia; ROTTER, JEROME - Harbor-Ucla Medical Center; GANZ, PETER - University Of California San Francisco (UCSF); GERTSZTEN, ROBERT - Beth Israel Deaconess Medical Center; TAYLOR, KENT - Harbor-Ucla Medical Center; RAFFIELD, LAURA - University Of North Carolina

Submitted to: Nature Communications
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/9/2025
Publication Date: 1/22/2026
Citation: 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., Gertszten, R.E., Taylor, K.D., Raffield, L.M. 2026. Cross-ancestry comparison of aptamer and antibody protein measures. Nature Communications. 17(1). Article 1054. https://doi.org/10.1038/s41467-025-67814-1.
DOI: https://doi.org/10.1038/s41467-025-67814-1

Interpretive Summary: Proteins in the blood are key indicators of health and disease, but different technologies used to measure them can give conflicting results, especially across populations of different ancestry. This study compared over 2,000 proteins measured by two leading technologies—SomaScan and Olink—in nearly 2,000 participants from diverse ancestral backgrounds. The researchers found that the same protein often appeared to have only modest agreement between the two platforms, and that some of these differences were related to genetic variants that are more common in certain ancestry groups. After accounting for these ancestry-related genetic differences, the agreement between technologies improved, and protein–disease relationships became more consistent. These findings show that genetic variation can distort how proteins are measured across technologies and ancestries, and that adjusting for these effects improves accuracy. The work is especially relevant for researchers and clinicians using proteomics data to understand disease biology or develop personalized treatments across diverse populations.

Technical Abstract: Measures from affinity-proteomics platforms often correlate poorly, challenging interpretation of protein associations with genetic variants and phenotypes. Here, we examine 2157 proteins measured on both SomaScan 7k and Olink Explore 3072 across 1930 participants with genetic similarity to European, African, East Asian, and Admixed American ancestry references. Inter-platform correlation coefficients for these 2157 proteins follow a bimodal distribution (median r=0.30). We evaluate protein measure associations with genetic variants, and find approximately 25-30% of the signals on each platform are likely driven by protein-altering variants. We highlight 80 proteins that correlate differently across ancestry groups likely in part due to differing protein-altering variant frequencies by ancestry. Furthermore, adjustment for protein-altering variants with opposite directions of effect by platform improves inter-platform protein measure correlation and results in more concordant genetic and phenotypic associations. Hence, protein-altering variants need to be accounted for across ancestries to facilitate platform-concordant and accurate protein measurement.