Phenotypic associations with the HMOX1 GT(n) repeat in European populations.

HO-1 is a key enzyme in the management of heme in humans. A GT(n) repeat length in the gene HMOX1, has previously been widely associated with a variety of phenotypes, including susceptibility and outcomes in diabetes, cancer, infections, and neonatal jaundice. However, studies are generally small and results inconsistent. In this study, we imputed the GT(n) repeat length in two European cohorts (UK Biobank, UK, n = 463,005, recruited 2006-onwards; and Avon Longitudinal Study of Parents and Children, ALSPAC, UK, n = 937, recruited 1990 onwards), with the reliability of imputation tested in other cohorts (1000 Genomes, Human Genome Diversity Project and UK-Personal Genome Project). Subsequently, we measured the relationship between repeat length and previously identified associations (diabetes, COPD, pneumonia and infection related mortality in UK Biobank; neonatal jaundice in ALSPAC) and performed a phenome-wide association study (PheWAS) in UK Biobank. Despite high quality imputation (correlation between true repeat length and imputed repeat length >0.9 in test cohorts), clinical associations were not identified in either the PheWAS or specific association studies. These findings are robust to definitions of repeat length and sensitivity analyses. Despite multiple smaller studies identifying associations across a variety of clinical settings; we could not replicate or identify any relevant phenotypic associations with the HMOX1 GT(n) repeat.

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© The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.