title: Replication of associations between genetic polymorphisms and chronic graft-versus-host disease.
abstract: Previous studies have identified single-nucleotide polymorphisms (SNPs) associated with the risk of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation. The current study determined whether these associations could be replicated in large cohorts of donors and recipients. Each SNP was tested with cohorts of patients having the same donor type (HLA-matched related, unrelated, or both) reported in the original publication, and testing was limited to the same genome (recipient or donor) and genetic model (dominant, recessive, or allelic) reported in the original study. The 21 SNPs reported in this study represent 19 genes, and the analysis encompassed 22 SNP association tests. The hazard ratio (HR) point estimates and risk ratio point estimates corresponding to odds ratios in previous studies consistently fall outside the 95% confidence intervals of HR estimates in the current study. Despite the large size of the cohorts available for the current study, the 95% confidence intervals for most HRs did not exclude 1.0. Three SNPs representing CTLA4, HPSE, and IL1R1 showed evidence of association with the risk of chronic GVHD in unrelated donor-recipient pairs from 1 cohort, but none of these associations was replicated when tested in unrelated donor-recipient pairs from an independent cohort. Two SNPs representing CCR6 and FGFR1OP showed possible associations with the risk of chronic GVHD in related donor-recipient pairs but not in unrelated donor-recipient pairs. These results remain to be tested for replication in other cohorts of related donor-recipient pairs.
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA.|Department of Medicine, University of Washington, Seattle, WA.
authors.forename: Paul J
authors.identifier: 0000-0001-9051-1215
authors.initials: PJ
authors.lastname: Martin
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Wenhong
authors.initials: W
authors.lastname: Fan
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA.|Department of Biostatistics, University of Washington, Seattle, WA.
authors.forename: Barry E
authors.initials: BE
authors.lastname: Storer
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA.
authors.forename: David M
authors.initials: DM
authors.lastname: Levine
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Lue Ping
authors.initials: LP
authors.lastname: Zhao
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA.|Department of Medicine, University of Washington, Seattle, WA.
authors.forename: Edus H
authors.initials: EH
authors.lastname: Warren
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA.|Department of Medicine, University of Washington, Seattle, WA.
authors.forename: Mary E D
authors.initials: ME
authors.lastname: Flowers
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA.|Department of Medicine, University of Washington, Seattle, WA.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA.|Department of Medicine, University of Washington, Seattle, WA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Carpenter
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA.|Division of Vaccines and Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Michael
authors.initials: M
authors.lastname: Boeckh
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, WA.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Hingorani
authors.affiliation: Department of Biostatistics & Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY.
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of Biostatistics & Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Hu
authors.affiliation: College of Pharmacy and.|College of Veterinary Medicine, The Ohio State University, Columbus, OH.
authors.forename: Leah
authors.initials: L
authors.lastname: Preus
authors.affiliation: Department of Biostatistics & Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY.
authors.forename: Song
authors.initials: S
authors.lastname: Liu
authors.affiliation: Center for International Blood and Marrow Transplant Research (CIBMTR), National Marrow Donor Program/Be The Match, Minneapolis, MN.
authors.forename: Stephen
authors.initials: S
authors.lastname: Spellman
authors.affiliation: CIBMTR, Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Zhu
authors.affiliation: CIBMTR, Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Pasquini
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY; and.
authors.forename: Philip
authors.initials: P
authors.lastname: McCarthy
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, CA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Stram
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, CA.
authors.forename: Xin
authors.initials: X
authors.lastname: Sheng
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, CA.
authors.forename: Loreall
authors.initials: L
authors.lastname: Pooler
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, CA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.affiliation: College of Pharmacy and.|College of Veterinary Medicine, The Ohio State University, Columbus, OH.
authors.forename: Lara
authors.initials: L
authors.lastname: Sucheston-Campbell
authors.affiliation: Department of Biostatistics & Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY.
authors.forename: Theresa
authors.initials: T
authors.lastname: Hahn
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA.|Department of Medicine, University of Washington, Seattle, WA.
authors.forename: John A
authors.initials: JA
authors.lastname: Hansen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D006086:Graft vs Host Disease / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014184:Transplantation, Homologous; D061349:Unrelated Donors; D055815:Young Adult