03128nas a2200577   4500000000100000000000100001008004100002260001200043653002500055653002100080653002000101653002800121100002000149700001600169700001400185700002300199700002200222700001900244700001900263700001900282700002200301700001900323700001800342700001400360700001700374700002200391700001400413700001600427700001800443700001700461700002100478700001900499700001700518700001700535700002100552700002000573700002300593700001800616700001900634700001700653700002000670700002300690700002400713700001800737245008100755856005500836300001400891490000800905520162300913022001402536       2026                            d  c2026-0910aComputational models10aData integration10aGene expression10aQuantitative Trait Loci1 aSanan Venkatesh1 aRoman Kosoy1 aZhenyi Wu1 aMarios Anyfantakis1 aChristian Dillard1 aPrashant N. M.1 aDavid Burstein1 aDeepika Mathur1 aChris Chatzinakos1 aBukola Ajanaku1 aFotis Tsetsos1 aBiao Zeng1 aSonali Gupta1 aRachel Bercovitch1 aAram Hong1 aClara Casey1 aMarcela Alvia1 aZhiping Shao1 aStathis Argyriou1 aKaren Therrien1 aTim Bigde li1 aPavan Auluck1 aDavid A. Bennett1 aStefano Marenco1 aVahram Haroutunian1 aKiran Girdhar1 aJaroslav Bendl1 aDonghoon Lee1 aJohn F. Fullard1 aGabriel E. Hoffman1 aGeorgios Voloudakis1 aPanos Roussos00aSingle-nucleus transcriptome-wide association study of human brain disorders  uhttps://www.nature.com/articles/s41586-026-10836-6  a1016-10260 v6573 aCommon brain disorders impose a substantial health burden, but localizing their genetic risk in the brain remains challenging1. Although genome-wide association studies have identified numerous loci associated with neuropsychiatric and neurodegenerative disorders, many of these loci lie in non-coding regions that influence gene expression in specific cell types2–5. Traditional bulk brain transcriptomic analyses, which often focus on European ancestry cohorts, average over cellular diversity, obscuring genetic risk-related changes in gene expression. Here we use single-nucleus gene expression profiles from the dorsolateral prefrontal cortex in the multi-ancestry PsychAD cohort to develop transcriptomic imputation models of genetically regulated expression across major brain cell types. Applying these models to neuropsychiatric and neurodegenerative disorders reveals thousands of gene–trait associations that are undetectable in bulk tissue analyses and resolves many signals to discrete neuronal, glial and immune cell populations. Cross-ancestry analyses in the Million Veteran Program confirm these associations, reveal pleiotropic effects of cell-type-specific predicted expression and demonstrate that trait-related dysregulation is conserved across ancestries, enabling mapping of causal genes and pathways. Together, these findings provide a cell-type-resolved and ancestry-aware atlas of genetically regulated expression in the human prefrontal cortex and illustrate how single-nucleus transcriptomics can sharpen gene discovery and therapeutic target prioritization for complex brain disorders.  a1476-4687