Gwangwoo coming back to Hanyang U with 2 papers [1.7]

Post date: Mar 10, 2016 2:44:53 AM

Dr. KIM Gwangwoo (PhD 2011) has recently published two papers in Nature Communication and PLoS One and will come back to Hanyang University Medical School on January 7, 2015. His postdoctoral fellowship ends at the Harvard Medical School/Broad Institute on December 31, 2014.

His Nat Commun publication is covered in Korean newspapers, for example,

http://vip.mk.co.kr/news/view/21/20/1235343.html

[1] Nat Commun. 2014 Dec 23;5:5902. doi: 10.1038/ncomms6902.

The HLA-DRβ1 amino acid positions 11-13-26 explain the majority of SLE-MHC associations.

Kim K, Bang SY, Lee HS, Okada Y, Han B, Saw WY, Teo YY, Bae SC.

Abstract: Genetic association of the major histocompatibility complex (MHC) locus is well established in systemic lupus erythematosus (SLE), but the causal functional variants in this region have not yet been discovered. Here we conduct the first fine-mapping study, which thoroughly investigates the SLE-MHC associations down to the amino acid level of major HLA genes in 5,342 unrelated Korean case-control subjects, taking advantages of HLA imputation with a newly constructed Asian HLA reference panel. The most significant association is mapped to amino acid position 13 of HLA-DRβ1 (P=2.48 × 10(-17)) and its proxy position 11 (P=4.15 × 10(-17)), followed by position 26 in a stepwise conditional analysis (P=2.42 × 10(-9)). Haplotypes defined by amino acid positions 11-13-26 support the reported effects of most classical HLA-DRB1 alleles in Asian and European populations. In conclusion, our study identifies the three amino acid positions at the epitope-binding groove of HLA-DRβ1 that are responsible for most of the association between SLE and MHC.

[2] PLoS One. 2014 Nov 14;9(11):e112546. doi: 10.1371/journal.pone.0112546. eCollection 2014.

Construction and application of a korean reference panel for imputing classical alleles and amino acids of human leukocyte antigen genes.

Kim K, Bang SY, Lee HS, Bae SC.

Abstract: Genetic variations of human leukocyte antigen (HLA) genes within the major histocompatibility complex (MHC) locus are strongly associated with disease susceptibility and prognosis for many diseases, including many autoimmune diseases. In this study, we developed a Korean HLA reference panel for imputing classical alleles and amino acid residues of several HLA genes. An HLA reference panel has potential for use in identifying and fine-mapping disease associations with the MHC locus in East Asian populations, including Koreans. A total of 413 unrelated Korean subjects were analyzed for single nucleotide polymorphisms (SNPs) at the MHC locus and six HLA genes, including HLA-A, -B, -C, -DRB1, -DPB1, and -DQB1. The HLA reference panel was constructed by phasing the 5,858 MHC SNPs, 233 classical HLA alleles, and 1,387 amino acid residue markers from 1,025 amino acid positions as binary variables. The imputation accuracy of the HLA reference panel was assessed by measuring concordance rates between imputed and genotyped alleles of the HLA genes from a subset of the study subjects and East Asian HapMap individuals. Average concordance rates were 95.6% and 91.1% at 2-digit and 4-digit allele resolutions, respectively. The imputation accuracy was minimally affected by SNP density of a test dataset for imputation. In conclusion, the Korean HLA reference panel we developed was highly suitable for imputing HLA alleles and amino acids from MHC SNPs in East Asians, including Koreans.