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Imputation of class I and II HLA loci using high‐density SNP s from I mmuno C hip and their associations with K awasaki disease in family‐based study
Author(s) -
Shrestha S.,
Wiener H. W.,
Aissani B.,
Shendre A.,
Tang J.,
Portman M. A.
Publication year - 2015
Publication title -
international journal of immunogenetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.41
H-Index - 47
eISSN - 1744-313X
pISSN - 1744-3121
DOI - 10.1111/iji.12190
Subject(s) - human leukocyte antigen , linkage disequilibrium , single nucleotide polymorphism , genetics , biology , snp , major histocompatibility complex , genotype , allele , mhc class i , imputation (statistics) , immunology , transmission disequilibrium test , antigen , gene , machine learning , missing data , computer science
Summary Kawasaki disease ( KD ) is the leading cause of acquired heart disease in children in most developed countries including the United States. The etiology of KD is not known; however, epidemiological and immunological data suggest infectious or immune‐related factors in the manifestation of the disease. Further, KD has several hereditary features that strongly suggest a genetic component to disease pathogenesis. Human leucocyte antigen ( HLA ) loci have also been reported to be associated with KD , but results have been inconsistent, in part, because of small study samples and varying linkage disequilibrium ( LD ) patterns observed across different ethnic groups. To maximize the informativeness of single nucleotide polymorphism ( SNP ) genotypes in the major histocompatibility ( MHC ) region, we imputed classical HLA I ( A, B, C ) and HLA II ( DRB 1, DQA 1, DQB 1 ) alleles using SNP 2 HLA method from genotypes of 6700 SNP s within the extended MHC region contained in the ImmunoChip among 112 White patients with KD and their biological parents from North America and tested their association with KD susceptibility using the transmission disequilibrium test. Mendelian consistency in the trios suggested high accuracy and reliability of the imputed alleles (class I = 97.5%, class II = 96.6%). While several SNP s in the MHC region were individually associated with KD susceptibility, we report over‐transmission of HLA ‐C*15 ( z = +2.19, P = 0.03) and under‐transmission of HLA ‐B*44 ( z = −2.49, P = 0.01) alleles from parents to patients with KD . HLA ‐B*44 has been associated with KD in other smaller studies, and both HLA ‐C*15 and HLA ‐B*44 have biological mechanisms that could potentially be involved in KD pathogenesis. Overall, inferring HLA loci within the same ethnic group, using family‐based information is a powerful approach. However, studies with larger sample sizes are warranted to evaluate the correlations of the strength and directions between the SNP s in MHC region and the imputed HLA alleles with KD .