A genome-wide association study of heparin-induced thrombocyto - penia using an electronic medical record

• DOI: 10.1160/th14-08-0670
• Publication Date: 2014-12-11T12:08:19Z
• Authors: Jason H. Karnes; Robert M. Cronin; Jerome Rollin; Alexander Teumer; Claire Pouplard; Christian M. Shaffer; Carmelo Blanquicett; Erica A. Bowton; James D. Cowan; Jonathan D. Mosley; Sara L. Van Driest; Peter E. Weeke; Quinn S. Wells; Tamam Bakchoul; Joshua C. Denny; Andreas Greinacher; Yves Gruel; Dan M. Roden
• Keywords: Genome-wide Association Study; Linkage Disequilibrium; Genetic Association; SNP

Summary Heparin-induced thrombocytopenia (HIT) is an unpredictable, potentially catastrophic adverse effect of heparin treatment resulting from immune response to platelet factor 4 (PF4)/heparin complexes. No genome-wide evaluations have been performed identify potential genetic influences on HIT. Here, we a association study (GWAS) and candidate gene using HIT cases controls identified electronic medical records (EMRs) coupled DNA biobank attempted replicate GWAS associations in independent cohort. We subsequently investigated GWAS-associated single nucleotide polymorphisms (SNPs) PF4/heparin antibodies non-heparin treated individuals. In recessive model, observed significant SNP (odds ratio [OR] 18.52; 95% confidence interval [CI] 6.33-54.23; p=3.18×10-9) with near the T-Cell Death-Associated Gene 8 (TDAG8). These SNPs are linkage disequilibrium missense TDAG8 SNP. trended toward replication analysis (OR 5.71; 0.47-69.22; p=0.17), was associated antibody levels positive patients 3.09; 1.14-8.13; p=0.02). study, at HLA-DRA were nominally 0.25; 0.15-0.44; p=2.06×10-6). Further warranted assess their influence risk developing