Multi-omics in the All Of Us Research Program expands mapping genetic mechanisms in health and disease

In the All of Us multi-omics cohort, proteomic (N = 10,043) and transcriptomic (N = 9,043) data enabled detection of 182,246 QTLs, with 59.4% (32,235) resolving to a single causal variant.

• Why it matters: Multi-omics mapping is needed to better uncover molecular mechanisms linking genetic variation to health and disease across diverse ancestry groups, beyond single-layer analyses.
• What they did: The study performed comprehensive expression, splicing, and protein quantitative trait locus (e/s/pQTL) analyses, including fine-mapping 54,255 QTLs to rare variants and assessing replication and target enrichment.
• The result: Rare variant QTLs were more likely ancestrally restricted, replicated across molecular layers, and were linked to Mendelian disease genes (OR = 1.4) and approved drug targets (OR = 1.3), while 5,186 variants showed effects including many absent from ClinVar.

AI summary of the abstract · may contain errors · not medical advice · read the paper.