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

Hamilton, Fergus, Mitchell, Ruth, Ghazal, Peter ORCID: https://orcid.org/0000-0003-0035-2228 and Timpson, Nic 2023. Phenotypic associations with the HMOX1 GT(n) repeat in European populations. American Journal of Epidemiology , kwad154. 10.1093/aje/kwad154

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Abstract

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.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Medicine
Publisher:	Oxford University Press
ISSN:	0002-9262
Date of First Compliant Deposit:	18 August 2023
Date of Acceptance:	6 July 2023
Last Modified:	16 Nov 2023 12:04
URI:	https://orca.cardiff.ac.uk/id/eprint/161906

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