Genome-wide association study of circulating retinol levels

Abstract

Retinol is one of the most biologically active forms of vitamin A and is hypothesized to influence a wide range of human diseases including asthma, cardiovascular disease, infectious diseases and cancer. We conducted a genome-wide association study of 5006 Caucasian individuals drawn from two cohorts of men: the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study and the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. We identified two independent single-nucleotide polymorphisms associated with circulating retinol levels, which are located near the transthyretin (TTR) and retinol binding protein 4 (RBP4) genes which encode major carrier proteins of retinol: rs1667255 (P =2.30× 10(-17)) and rs10882272 (P =6.04× 10(-12)). We replicated the association with rs10882272 in RBP4 in independent samples from the Nurses' Health Study and the Invecchiare in Chianti Study (InCHIANTI) that included 3792 women and 504 men (P =9.49× 10(-5)), but found no association for retinol with rs1667255 in TTR among women, thus suggesting evidence for gender dimorphism (P-interaction=1.31× 10(-5)). Discovery of common genetic variants associated with serum retinol levels may provide further insight into the contribution of retinol and other vitamin A compounds to the development of cancer and other complex diseases.

Figure 1.

LD structure of chromosome 10. P-values generated from ATBC and PLCO data. LR, the recombination rate on a logarithmic scale with 12 being ‘notable’ for a hotspot.

Figure 2.

LD structure of chromosome 18. P-values generated from ATBC and PLCO data. LR, the recombination rate on a logarithmic scale with 12 being ‘notable’ for a hotspot.

Figure 3.

Quantile–quantile plot of 562 105 SNPs from the pooled analysis of the two GWAS scans (n = 5 006; λ_GC = 1.018).