Rare and common genetic variants shape single-cell immune gene expression.

TenK10K phase 1 links genetic variants to cell-type-specific immune gene expression across 28 immune cell types, mapping common regulatory variants for 83% of 21,404 genes.

• Why it matters: Genetic regulation of cell states and types is incompletely understood, especially for rare and low-frequency variants that remain largely uncharacterized in their cell-specific effects.
• What they did: The study used single-cell RNA sequencing from over 5 million cells and matched whole-genome sequencing from 1,925 individuals, mapping common and rare variant effects with a method that models single cells directly.
• The result: It found cumulative rare-variant signals for 47% of the tested genes and showed about half of genetic effects are observed only in one or a few cell types, enabling cell-type-specific eQTL interpretation.