A phylogenetic protein-coding genome-phenome map of complex traits across 224 primate species.

Complex traits arise from networks of coding and regulatory loci, making their genetic basis difficult to resolve. Macroevolutionary studies leverage millions of years of divergence across species to uncover fixed genomic changes invisible to within-species approaches like GWAS. Studying variation in mammals and primates offers insights into the evolution of complex traits and provides a complementary framework for generating hypotheses in biomedical research. Here, we present the first phylogenetic protein-coding, primate-wide genome-phenome map (P3GMap), spanning 263 traits across 224 primate species, which we release through the Primate Genome-Phenome Archive (PGA, https://pgarchive.github.io). Using two complementary approaches, convergent amino acid substitutions and relative evolutionary rates, we link protein-coding variation to complex phenotypes and identify thousands of gene-trait associations, including lineage-specific adaptations in diet, immunity, and lifespan. One sentence summaryCross-species genome-phenome mapping in primates reveals thousands of protein-coding variants linked to complex trait evolution.