Genetic determinants and phenotypic consequences of blood T-cell proportions in 207,000 diverse individuals

T-cells play a critical role in multiple aspects of human health and disease. However, to date the genetic determinants of human T-cell abundance have not been studied at scale because assays quantifying T-cell abundance are not widely used in clinical or research settings. The complete blood count clinical assay quantifies lymphocyte abundance which includes T-cells, B-cells, and NK-cells. To address this gap, we directly estimate T-cell fractions from whole genome sequencing data in over 200,000 individuals from the multi-ethnic TOPMed and All of Us studies. We identified 27 loci associated with T-cell fraction. Interrogating electronic health records identified clinical phenotypes associated with T-cell fraction, including notable changes in T-cell proportions that were highly dynamic over the course of pregnancy. In summary, by estimating T-cell fraction, we obtained new insights into the genetic regulation of T-cells and identified disease consequences of T-cell fractions across the human phenome.