Ribosomal DNA copy number variation associates with hematological profiles and renal function in the UK Biobank

Francisco Rodriguez-Algarra; David M Evans; Vardhman K Rakyan

doi:10.1016/j.xgen.2024.100562

Ribosomal DNA copy number variation associates with hematological profiles and renal function in the UK Biobank

Cell Genom. 2024 May 10:100562. doi: 10.1016/j.xgen.2024.100562. Online ahead of print.

Authors

Francisco Rodriguez-Algarra¹, David M Evans², Vardhman K Rakyan³

Affiliations

¹ The Blizard Institute, School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
² Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia; Frazer Institute, The University of Queensland, Brisbane, QLD 4102, Australia; MRC Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, UK.
³ The Blizard Institute, School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK. Electronic address: v.rakyan@qmul.ac.uk.

PMID: 38749448
DOI: 10.1016/j.xgen.2024.100562

Abstract

The phenotypic impact of genetic variation of repetitive features in the human genome is currently understudied. One such feature is the multi-copy 47S ribosomal DNA (rDNA) that codes for rRNA components of the ribosome. Here, we present an analysis of rDNA copy number (CN) variation in the UK Biobank (UKB). From the first release of UKB whole-genome sequencing (WGS) data, a discovery analysis in White British individuals reveals that rDNA CN associates with altered counts of specific blood cell subtypes, such as neutrophils, and with the estimated glomerular filtration rate, a marker of kidney function. Similar trends are observed in other ancestries. A range of analyses argue against reverse causality or common confounder effects, and all core results replicate in the second UKB WGS release. Our work demonstrates that rDNA CN is a genetic influence on trait variance in humans.

Keywords: UK Biobank; blood; copy number variation; genetic associations; kidney; neutrophils; repetitive features; ribosomal DNA; ribosome.