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

Hannah Poisner, Annika Faucon, Nancy Cox and Alexander G. Bick ()
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Hannah Poisner: Vanderbilt University School of Medicine
Annika Faucon: Vanderbilt University School of Medicine
Nancy Cox: Vanderbilt University School of Medicine
Alexander G. Bick: Vanderbilt University School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-51095-1

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