Genetic influences on circulating retinol and its relationship to human health

Abstract

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.

β‐Carotene Impacts the Liver microRNA Profile in a Sex‐Specific Manner in Mouse Offspring of Western Diet‐Fed Mothers: Results from Microarray Analysis by Direct Hybridization

“…Forty-seven of these overlapping genes (55% percent) were targeted by miRNAs with opposite (down or up) regulation between sexes. Nutritional or functional associations to BC or BC derivates are described in the literature for some of the overlapping genes, such as Cntn2 [60], Etv3 [61], Foxp2 [62], Otud7b [63], and Pbxl [64]. Additionally, among the 47 predicted overlapping targets of miRNAs affected in opposite senses across sexes was the Rora gene encoding the retinoic acid receptor-related orphan receptor alpha transcription factor.…”