Center for Medical Ethics and Health Policy Staff Publications
Publication Date
11-12-2024
Journal
Blood Advances
DOI
10.1182/bloodadvances.2024012776
PMID
39189922
PMCID
PMC11538615
PubMedCentral® Posted Date
8-30-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Humans, Purpura, Thrombocytopenic, Idiopathic, Child, Wnt Signaling Pathway, Female, Male, Genome-Wide Association Study, Child, Preschool, Adolescent, Genetic Predisposition to Disease, Genetic Variation, Polymorphism, Single Nucleotide, Infant, Genotype
Abstract
Through the use of genetic sequencing, molecular variants driving autoimmunity are increasingly identified in patients with chronic and refractory immune cytopenias. With the goal of discovering genetic variants that predispose to pediatric immune thrombocytopenia (ITP) or increase risk for chronic disease, we conducted a genome-wide association study in a large multi-institutional cohort of pediatric patients with ITP. A total of 591 patients were genotyped using an Illumina Global Screening Array BeadChip. Six variants met genome-wide significance in comparison between children with ITP and a cohort of healthy children. One variant in NAV2 was inversely associated with ITP (adjusted odds ratio [aOR], 0.52; P = 3.2 × 10−11). Two other variants in close proximity to NKD1 were also inversely associated with ITP (aOR, 0.43; P = 8.86 × 10−15; aOR, 0.48; P = 1.84 × 10−16). These genes have been linked to the canonical Wnt signaling pathway. No variants met genome-wide significance in comparison of those with ITP that self-resolved in < 1 year versus those who developed chronic ITP. This study identifies genetic variants that may contribute to ITP risk and raises a novel pathway with a potential role in ITP pathogenesis.
Graphical Abstract