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Updated: Oct 13, 2026

Measurement of Carotenoids in Perifovea using the Macular Pigment Reflectometer
Published on: January 29, 2020
Genetic ancestry and genotype-by-diet interactions shape plasma carotenoid metabolism in humans
Abstract:
Interindividual variation in circulating nutrients reflects intersections of diet, ancestry and host genetics, yet genotype-diet regulation of nutrient metabolism remains difficult to map in diverse populations. Here, we integrate multi-ancestry genome-wide genotyping and targeted sequencing with a longitudinal randomized dose-response trial to study species-specific plasma carotenoid metabolism. Using plasma carotenoid concentrations as integrated readouts in two deeply phenotyped, multi-ancestry U.S. cohorts: a discovery cohort (n = 213) and an intervention/replication cohort (n = 162), we show that SNP-based heritability varies substantially across carotenoid species and ancestry groups (h²=0.08-0.44), with plasma β-cryptoxanthin exhibiting the highest estimate and ancestry-dependent enrichment. GWAS identified β-cryptoxanthin associated loci at 3q13 ( IGSF11 region, rs80316816, P = 6.25x10-10, β = 0.74) and 19p13 ( R3HDM4/MED16 region, rs28468554, P = 6.26x10-9, β=-0.46), collectively explaining over 30% of β-cryptoxanthin variance in the discovery cohort. Crucially, in the intervention cohort, 3q13 variants showed genotype-dependent, dose-specific effects on β-cryptoxanthin response to supplementation. Targeted sequencing implicated the PKD1L2-BCO1 locus for β-carotene (Padj = 0.04, β=-1.3 to -0.3), and rare predicted-to-be-damaging variants in carotenoid- and lipid-related genes, including BCO1 , CETP and APOA1 , among individuals with extreme carotenoid concentration phenotypes. Together, these findings show how genetic diversity and genotype-diet interactions shape diet-responsive nutrient metabolism, advance a framework for precision nutrition genetics.
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