- Title
- Genetic influences on circulating retinol and its relationship to human health
- Creator
- Reay, William R.; Kiltschewskij, Dylan J.; Albanes, Demetrius; Cairns, Murray J.; Di Biase, Maria A.; Gerring, Zachary F.; Kundu, Kousik; Surendran, Praveen; Greco, Laura A.; Clarke, Erin D.; Collins, Clare E.; Mondul, Alison M.
- Relation
- NHMRC.1121474 https://purl.org/au-research/grants/nhmrc/1121474
- Relation
- Nature Communications Vol. 15, Issue 1, no. 1490
- Publisher Link
- http://dx.doi.org/10.1038/s41467-024-45779-x
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2024
- Description
- Retinol is a fat-soluble vitamin that plays an essential role in many biological processes throughout the human lifespan. Here, we perform the largest genome-wide association study (GWAS) of retinol to date in up to 22,274 participants. We identify eight common variant loci associated with retinol, as well as a rare-variant signal. An integrative gene prioritisation pipeline supports novel retinol-associated genes outside of the main retinol transport complex (RBP4:TTR) related to lipid biology, energy homoeostasis, and endocrine signalling. Genetic proxies of circulating retinol were then used to estimate causal relationships with almost 20,000 clinical phenotypes via a phenome-wide Mendelian randomisation study (MR-pheWAS). The MR-pheWAS suggests that retinol may exert causal effects on inflammation, adiposity, ocular measures, the microbiome, and MRI-derived brain phenotypes, amongst several others. Conversely, circulating retinol may be causally influenced by factors including lipids and serum creatinine. Finally, we demonstrate how a retinol polygenic score could identify individuals more likely to fall outside of the normative range of circulating retinol for a given age. In summary, this study provides a comprehensive evaluation of the genetics of circulating retinol, as well as revealing traits which should be prioritised for further investigation with respect to retinol related therapies or nutritional intervention.
- Subject
- evaluation; genetics; genome-wide association study; Mendelian randomisation study; retinol; vitamins
- Identifier
- http://hdl.handle.net/1959.13/1515083
- Identifier
- uon:56877
- Identifier
- ISSN:2041-1723
- Rights
- This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
- Language
- eng
- Full Text
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