Causal Associations of Red Cell Distribution Width with Rheumatoid Arthritis and Congestive Heart Failure: A Phenome-Wide Mendelian Randomization Study.

Abstract

Red cell distribution width (RDW) has been reported to be associated with many diseases, but there is no conclusive evidence for any causal relationship. This study aims to explore to determine the causal effects of high RDW on health with the help of phenome-wide association study (PheWAS), genome-wide association study (GWAS), and Mendelian randomization (MR). The data was derived from the UK Biobank and the population was selected to include white British with complete RDW data at baseline and similar genetic ancestry. The eligible subjects were divided into two non-overlapping groups using random sampling in a ratio of 8:2, with the former for PheWAS and the latter for GWAS. MR analysis was performed to determine whether there was a causal association between RDW and disease outcomes. After multiple corrections, 222 phenotypes associated with RDW were identified with PheWAS. According to GWAS, RDW was associated with 29 independent genetic signals. MR analysis confirmed that RDW had a statistically significant causal association with rheumatoid arthritis and congestive heart failure. Our study provides new evidence that sheds light on the controversial question of whether RDW is associated with disease risk.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-024-00172-y.