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Article: SNP-based HLA allele tagging, imputation and association with antiepileptic drug-induced cutaneous reactions in Hong Kong Han Chinese

TitleSNP-based HLA allele tagging, imputation and association with antiepileptic drug-induced cutaneous reactions in Hong Kong Han Chinese
Authors
Issue Date2018
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/tpj/
Citation
The Pharmacogenomics Journal, 2018, v. 18 n. 2 p. 340-346 How to Cite?
AbstractHuman 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.
Persistent Identifierhttp://hdl.handle.net/10722/259620
ISSN
2023 Impact Factor: 2.9
2023 SCImago Journal Rankings: 0.659
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorGui, H-
dc.contributor.authorKwok, M-
dc.contributor.authorBaum, LW-
dc.contributor.authorSham, PC-
dc.contributor.authorKwan, P-
dc.contributor.authorCherny, SS-
dc.date.accessioned2018-09-03T04:10:59Z-
dc.date.available2018-09-03T04:10:59Z-
dc.date.issued2018-
dc.identifier.citationThe Pharmacogenomics Journal, 2018, v. 18 n. 2 p. 340-346-
dc.identifier.issn1470-269X-
dc.identifier.urihttp://hdl.handle.net/10722/259620-
dc.description.abstractHuman 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.-
dc.languageeng-
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/tpj/-
dc.relation.ispartofThe Pharmacogenomics Journal-
dc.titleSNP-based HLA allele tagging, imputation and association with antiepileptic drug-induced cutaneous reactions in Hong Kong Han Chinese-
dc.typeArticle-
dc.identifier.emailBaum, LW: lwbaum@hku.hk-
dc.identifier.emailSham, PC: pcsham@hku.hk-
dc.identifier.emailCherny, SS: cherny@hku.hk-
dc.identifier.authoritySham, PC=rp00459-
dc.identifier.authorityCherny, SS=rp00232-
dc.identifier.doi10.1038/tpj.2017.11-
dc.identifier.pmid28398356-
dc.identifier.scopuseid_2-s2.0-85017435967-
dc.identifier.hkuros289186-
dc.identifier.volume18-
dc.identifier.issue2-
dc.identifier.spage340-
dc.identifier.epage346-
dc.identifier.eissn1473-1150-
dc.identifier.isiWOS:000431187500018-
dc.publisher.placeUnited Kingdom-
dc.identifier.issnl1470-269X-

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