Multi-omic characterization of the Hispanic/Latino blood lipidome reveals an additional locus and attenuated genetic prediction

Authors

• Wanying Zhu
• Hung-Hsin Chen
• Heather M. Highland
• Corey Giles, Baker Heart and Diabetes Institute
• Peter J. Meikle, Baker Heart and Diabetes Institute
• Joanne Curran, The University of Texas Rio Grande ValleyFollow
• Joseph B. McCormick, University of Texas Health Science Center at Houston
• Susan P. Fisher-Hoch, University of Texas Health Science Center at Houston
• Kari E. North, University of Texas Health Science Center at Houston

Document Type

Article

Publication Date

10-2026

Abstract

While lipids have been extensively investigated, genetic regulation of the circulating lipidome in diverse populations remains poorly understood. We conducted a lipidome-wide genome-wide association study (GWAS) of 830 lipid species in 2,287 Hispanic/Latino participants and performed predictive modeling across omics layers. We identified 7,593 genome-wide significant SNPs mapping to 208 genes. Conditional analysis disentangled the long-range linkage disequilibrium artifacts from the pleiotropic FADS1/2/3 cluster. Separately, we discovered an association at the GPLD1 locus for a circulating ceramide. Colocalization revealed shared genetic architecture with conventional lipids alongside distinct, species-specific pathways. Incorporating Native/Indigenous American expression quantitative trait loci (eQTLs) within a multi-omic framework uncovered 62 likely regulatory genes missed by European-centric gene expression models. Finally, genetically regulated predictive models demonstrated performance declining from transcriptomics to proteomics to lipidomics, reflecting increased distance from gene action along the molecular cascade. Our study provides a genetic landscape of lipid metabolism in a highly burdened population and highlights the challenges in predicting lipid abundance.

Comments

© 2026 The Authors. Published by Elsevier Inc. on behalf of American Society of Human Genetics. http://creativecommons.org/licenses/by-nc-nd/4.0/

Recommended Citation

Zhu, W., Chen, H., Highland, H. M., Giles, C., Meikle, P. J., Lin, P., Petty, L. E., Polikowsky, H. G., Petty, A. S., Anwar, M. Y., Zhang, X., Curran, J. E., Frankel, E. G., Roshani, R., Landman, J. M., Castrodad-Rivera, G. S., Herndon, C., McCormick, J. B., Fisher-Hoch, S. P., … Below, J. E. (2026). Multi-omic characterization of the Hispanic/Latino blood lipidome reveals an additional locus and attenuated genetic prediction. Human Genetics and Genomics Advances, 7(4), 100664. https://doi.org/10.1016/j.xhgg.2026.100664  

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Publication Title

Human Genetics and Genomics Advances

DOI

10.1016/j.xhgg.2026.100664