Evaluation of published single nucleotide polymorphisms associated with acute graft versus host disease

Publication Type:

Journal Article


Blood, Volume 119, Issue 22, p.5311-5319 (2012)


2012, Center-Authored Paper, Clinical Research Division, Consortium Authored Paper, Feb 2012, February 2012, Genomics Core Facility, Public Health Sciences Division, Research Trials Office Core Facility - Biostatistics Service, Shared Resources


Candidate genetic associations with acute graft versus host disease (aGVHD) were evaluated using genotyped and imputed single nucleotide polymorphism (SNP) data from genome-wide scans of 1,298 allogeneic hematopoietic cell transplantation (HCT) donors and recipients. Of 40 previously reported candidate SNPs, six (CD31, CTLA4, HPSE, IL23R, IL6 and TNF) were successfully genotyped, ten (CD31, IL1β, IL2, IL10, MTHFR, RFC1, TNF, and TNFRII) were imputed and passed criteria for analysis. Patient and donor genotypes were assessed for association with grades IIb-IV and III-IV aGVHD, stratified by donor type, in univariate and multivariate allelic, recessive and dominant models. Use of imputed genotypes to replicate previous IL10 associations was validated. Similar to previous publications, the IL6 donor genotype for rs1800795 was associated with a 20 to 50% increased risk for grade IIb-IV aGVHD after unrelated HCT in the allelic (adjusted P=0.011) and recessive (adjusted P=0.0013) models. The donor genotype was associated with a 60% increase in risk for grade III-IV aGVHD after related HCT (adjusted P=0.028). Other associations were found for IL2, CTLA4, HPSE and MTHFR, but were inconsistent with original publications. These results illustrate the advantages of using imputed SNP data in genetic analyses and demonstrate the importance of validation in genetic association studies.