title: SNP-based HLA allele tagging, imputation and association with antiepileptic drug-induced cutaneous reactions in Hong Kong Han Chinese.
abstract: Human leukocyte antigen (HLA) genes control the regulation of the human immune system and are involved in immune-related diseases. Population surveys on relationships between single nucleotide polymorphisms (SNP) and HLA alleles are essential to conduct genetic association between HLA variants and diseases. Samples were obtained from our in-house database for epilepsy genetics and pharmacogenetics research. Using 184 epilepsy patients with both genome-wide SNP array and HLA-A/B candidate gene sequencing data, we sought tagging SNPs that completely represent sixHLA risk alleles; in addition, a Hong Kong population-specific reference panel was constructed for SNP-based HLA imputation. The performance of our new panel was compared to a recent Han Chinese panel. Finally, genetic associations of HLA variants with mild skin rash were performed on the combined sample of 408 patients. Common SNPs rs2571375 and rs144295468 were found to successfully tag HLA risk alleles A*31:01 and B*13:01, respectively. HLA-B*15:02 can be predicted by rs144012689 with >95% sensitivity and specificity. The imputation reference panel for the Hong Kong population had comparable performance to the Han Chinese panel due to the large sample size for common HLA alleles, though it retained discordance for imputing rare alleles. No significant genetic associations were found between HLA genetic variants and mild skin rash induced by aromatic antiepileptic drugs. This study provides new information on the genetic structure of HLA regions in the Hong Kong population by identifying tagging SNPs and serving as a reference panel. Moreover, our comprehensive genetic analyses revealed no significant association between HLA alleles and mild skin rash in Hong Kong Han Chinese.
authors.affiliation: Center for Genomic Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.|Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, MI, USA.
authors.forename: H
authors.initials: H
authors.lastname: Gui
authors.affiliation: Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: M
authors.initials: M
authors.lastname: Kwok
authors.affiliation: Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: L
authors.initials: L
authors.lastname: Baum
authors.affiliation: Center for Genomic Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.|Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.|The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: P C
authors.initials: PC
authors.lastname: Sham
authors.affiliation: Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China.|Departments of Medicine and Neurology, The University of Melbourne, Royal Melbourne Hospital, Parkville, VIC, Australia.
authors.forename: P
authors.initials: P
authors.lastname: Kwan
authors.affiliation: Center for Genomic Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.|Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.|The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: S S
authors.initials: SS
authors.lastname: Cherny
mesh_terms: D000483:Alleles; D000927:Anticonvulsants / Q000009:adverse effects*; D044466:Asian People / Q000235:genetics*; D030541:Databases, Genetic / Q000706:statistics & numerical data; D004827:Epilepsy / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D005076:Exanthema / Q000139:chemically induced* / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D006680:HLA Antigens / Q000235:genetics*; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D000927:Anticonvulsants; D006680:HLA Antigens