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Variation in carotenoid bioavailability at individual and population levels might depend on host-related factors where genetic variation has a part to play. It manifests itself through the proteins involved in carotenoid intestinal absorption and metabolism, blood lipoprotein transport, or tissue uptake. This study aims to identify novel SNPs which could be associated with carotenoid serum concentrations. A total of 265 self-reported healthy individuals of Lithuanian origin were genotyped (Illumina HumanOmniExpress-12v1.0 or v1.1 and Infinium OmniExpress-24v1.2 arrays) and fasting blood serum concentrations of β- and α-carotene, β-cryptoxanthin, lycopene, lutein, and zeaxanthin were measured (Shimadzu Prominence HPLC system). According to the individual carotenoid concentrations, the cohort was subdivided into quartiles. Q1 and Q4 were used for the following association analysis. The set of 2883 SNPs in 109 potential candidate genes (assumed for a direct or indirect role in carotenoid bioavailability) was analyzed. Liver X receptor alpha ( NR1H3 ) "transport" polymorphisms rs2279238 ( p  = 2.129 × 10 -5 ) and rs11039155 ( p  = 2.984 × 10 -5 ), and apolipoprotein B ( APOB ) "transport" polymorphism rs550619 ( p  = 4.844 × 10 -5 ) were associated with higher zeaxanthin concentration. Retinol dehydrogenase 12 ( RDH12 ) "functional partner" polymorphism rs756473 ( p  = 7.422 × 10 -5 ) was associated with higher lycopene concentration. Twenty-one cytochrome P450 ( CYP2C9 , CYP2C18, and CYP2C19 ) "metabolism" polymorphisms in locus 10q23.33 were significantly associated with higher β-carotene concentration. To conclude, four novel genomic loci were found to be associated with carotenoid serum levels. Zeaxanthin, lycopene, and β-carotene serum concentrations might depend on genetic variation in NR1H3 , APOB , RDH12 and CYP2C9, CYP2C18, and CYP2C19 genes., Competing Interests: All authors declare no conflicting interests., (© 2022 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)