Genome-wide association of pica within a cohort of volunteer blood donors potentially implicates the gene encoding neuropeptide VF

Abstract

BACKGROUND: Pica is an eating disorder characterized by the persistent craving and consumption of non-food substances such as ice, chalk, starch, or raw pasta. Pica symptoms are more common in people with iron deficiency and resolve upon treatment. Without iron supplementation, volunteer blood donors can become iron deficient after repeated donations, making them an ideal population to study pica.

STUDY DESIGN AND METHODS: A genome-wide association study (GWAS) was conducted with 12,157 volunteer blood donors within the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) RBC-omics study. Three pica outcomes of interest were evaluated, including ice-only consumption, non-ice consumption, or either type of pica (combined). Candidate single nucleotide polymorphisms (SNPs) were tested for replication using all of us (AoU).

RESULTS: Within REDS-III, 2.4% of donors reported pica symptoms, and nine genome-wide significant SNPs were identified as associated with pica. Within a stratified European population of 7493 REDS-III donors, seven genome-wide significant SNPs were identified. Both overall and in the European stratum, ferritin levels were lower in pica cases than controls (36.0 ± 43.2 ng/mL vs. 53.3 ± 69.2 ng/mL overall and 33.8 ± 41.0 ng/mL vs. 43.8 ± 55.3 ng/mL). Of these, one SNP, rs73277282, near the gene encoding the neuropeptide VF (NPVF) replicated in the AoU dataset (REDS-III p = 1.53 x 10-8; AoU p = .02).

DISCUSSION: Neuropeptide VF has been previously shown to regulate food intake and energy balance, suggesting that polymorphisms associated with its expression may synergize with iron deficiency to produce pica behaviors.