ArticleNature communications2026
Mapping genetic regulation of gene expression to cellular contexts identifies long non-coding RNAs associated with brain disorders.
Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
How genetic variation regulates long non-coding RNA (lncRNA) expression across brain cell types remains poorly understood. A major barrier is the resolution-power trade-off between bulk and single-nucleus expression quantitative trait locus (eQTL) studies. Here, we quantify gene expression from cortical RNA-seq of 2443 individuals using an expanded transcriptome annotation and perform transcriptome-wide interaction eQTL mapping with deconvolution-derived cell-type proportions. Among 17,541 analyzed lncRNAs, we identify 3763 lncRNAs with cellular-context-dependent effects, of which 2,783 (74%) are not annotated by GENCODE. Colocalization with genome-wide association studies (GWAS) of brain-related traits identifies 118 lncRNA-trait colocalization events, approximately two-thirds of which are detectable only after modeling cellular context. Our study establishes a map of cellular-context-dependent genetic regulation in the human brain, providing a basis for nominating lncRNAs with potential roles in mediating genetic risk for brain disorders.
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