PMID- 30718717
OWN - NLM
STAT- MEDLINE
DCOM- 20200820
LR  - 20200820
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 9
IP  - 1
DP  - 2019 Feb 4
TI  - Understanding HLA associations from SNP summary association statistics.
PG  - 1337
LID - 10.1038/s41598-018-37840-9 [doi]
LID - 1337
AB  - Strong genetic associations in the region containing human leukocyte antigen 
      (HLA) genes have been well-documented in various human immune disorders. 
      Imputation methods to infer HLA variants from single nucleotide polymorphism 
      (SNP) genotypes are currently used to understand HLA associations with a trait of 
      interest. However, it is challenging for some researchers to obtain 
      individual-level SNP genotype data or reference haplotype data. In this study, we 
      developed and evaluated a new method, DISH (direct imputing summary association 
      statistics of HLA variants), for imputing summary association statistics of HLA 
      variants from SNP summary association statistics based on linkage disequilibria 
      in Asian and European populations. Disease association Z scores in DISH were 
      highly correlated with those from imputed HLA genotypes in null model datasets 
      (r = 0.934 in Asians; r = 0.960 in Europeans). We applied DISH to two previous 
      GWAS datasets in Asian systemic lupus erythematosus and European rheumatoid 
      arthritis populations. There was a high correlation between Z scores in the DISH 
      and HLA genotype imputations, showing the same disease-susceptible and protective 
      alleles. This study illustrated the usefulness of the DISH method in 
      understanding and identifying disease-associated HLA variants in human diseases 
      while maintaining individual-level data security.
FAU - Lim, Jiwoo
AU  - Lim J
AD  - Department of Biology, Kyung Hee University, Seoul, Republic of Korea.
FAU - Bae, Sang-Cheol
AU  - Bae SC
AD  - Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, 
      Seoul, Republic of Korea.
FAU - Kim, Kwangwoo
AU  - Kim K
AUID- ORCID: 0000-0001-8926-6216
AD  - Department of Biology, Kyung Hee University, Seoul, Republic of Korea. 
      kkim@khu.ac.kr.
LA  - eng
GR  - 076113/WT_/Wellcome Trust/United Kingdom
GR  - 085475/WT_/Wellcome Trust/United Kingdom
GR  - 090355/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190204
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Alleles
MH  - Arthritis, Rheumatoid/genetics/pathology
MH  - *Genetic Predisposition to Disease
MH  - Genome-Wide Association Study/*statistics & numerical data
MH  - Genotype
MH  - HLA Antigens/*genetics
MH  - Haplotypes/genetics
MH  - Humans
MH  - Linkage Disequilibrium/genetics
MH  - Phenotype
MH  - Polymorphism, Single Nucleotide/*genetics
PMC - PMC6362191
COIS- The authors declare no competing interests.
EDAT- 2019/02/06 06:00
MHDA- 2020/08/21 06:00
PMCR- 2019/02/04
CRDT- 2019/02/06 06:00
PHST- 2018/08/08 00:00 [received]
PHST- 2018/12/11 00:00 [accepted]
PHST- 2019/02/06 06:00 [entrez]
PHST- 2019/02/06 06:00 [pubmed]
PHST- 2020/08/21 06:00 [medline]
PHST- 2019/02/04 00:00 [pmc-release]
AID - 10.1038/s41598-018-37840-9 [pii]
AID - 37840 [pii]
AID - 10.1038/s41598-018-37840-9 [doi]
PST - epublish
SO  - Sci Rep. 2019 Feb 4;9(1):1337. doi: 10.1038/s41598-018-37840-9.