Supplementary Material for: The CAPN2/CAPN8 Locus on Chromosome 1q Is Associated with Variation in Serum Alpha-Carotene Concentrations

<p><b><i>Background/Aims:</i></b> Alpha-carotene is a provitamin A carotenoid present in fruits and vegetables. Higher serum concentrations of α-carotene have been associated with lower risk of cancer and all-cause mortality. Previous studies have suggested that genetic variants influence serum concentrations of provitamin A carotenoids, but to date no variants have been robustly associated with serum α-carotene concentrations. The aim of this study was to identify genetic associations with serum α-carotene concentrations using the genome-wide association study (GWAS) approach. <b><i>Methods:</i></b> A GWAS of serum α-carotene concentrations was conducted in 433 Old Order Amish adults who had consumed a 6-day controlled diet. Linear regression models adjusting for age, gender, and family structure were utilized to evaluate associations between genetic variants and serum α-carotene concentrations. <b><i>Results:</i></b> Genome-wide significant associations with α-carotene concentrations were observed for loci on chromosome 1q41 between the genes <i>CAPN2</i> and <i>CAPN8</i> (rs12137025, <i>p</i> = 3.55 × 10<sup>-8</sup>), chromosome 2p21 in <i>PRKCE</i> (rs2594495, <i>p</i> = 1.01 × 10<sup>-8</sup>), and chromosome 4q34 (rs17830069, <i>p</i> = 2.89 × 10<sup>-8</sup>). <b><i>Conclusions:</i></b> We identified 3 novel loci associated with serum α-carotene concentrations among a population that consumed a controlled diet. While replication is necessary, the <i>CAPN2/CAPN8</i> locus provides compelling evidence for an association with serum α-carotene concentrations and may suggest a relationship with the development and progression of cancers.</p>