PMID- 35221124
OWN - NLM
STAT- MEDLINE
DCOM- 20220426
LR  - 20220426
IS  - 1879-1166 (Electronic)
IS  - 0198-8859 (Linking)
VI  - 83
IP  - 5
DP  - 2022 May
TI  - HLA-disease association and pleiotropy landscape in over 235,000 Finns.
PG  - 391-398
LID - S0198-8859(22)00035-0 [pii]
LID - 10.1016/j.humimm.2022.02.003 [doi]
AB  - The human leukocyte antigen (HLA) system is the single most important genetic 
      susceptibility factor for many autoimmune diseases and immunological traits. For 
      systematic population-level analysis of HLA-phenotype association landscape we 
      imputed the alleles of classical HLA genes in a discovery cohort of 146,630 and 
      replication cohort of 89,340 Finns of whom SNP genotype data and 3,355 disease 
      phenotypes were available as part of the FinnGen project. In total, 3,649 
      statistically significant single HLA allele associations in 368 phenotypes were 
      found. Known susceptibility associations clearly dominated the landscape but we 
      discovered also a few previously poorly established HLA associations such as 
      DQA1*01:03 and DQB1*06:03 with mental and behavioural disorders due to 
      cannabinoids (p-value = 10(-5); beta = 0.6). As certain HLAs were found to be 
      involved in both autoimmune and infectious diseases, we studied further the 
      independence of their associations and statistical pleiotropy. We found that 
      altogether 11 shared HLA alleles were associated independently with both 
      autoimmune and infectious diseases. The most prominent of these were DQA1*03:01 
      and DQB1*03:02 both of which associated with three infectious and three 
      autoimmune phenotypes. All the shared HLAs showed risk effects in both disease 
      groups, suggesting that infections can increase the risk for autoimmune diseases. 
      The population-level landscape analysis is an excellent resource for estimating 
      the contribution and genetic models of HLA genes in many different phenotypes and 
      for fine-mapping primary associations.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Ritari, Jarmo
AU  - Ritari J
AD  - Finnish Red Cross Blood Service, Helsinki, Finland. Electronic address: 
      jarmo.ritari@bloodservice.fi.
FAU - Koskela, Satu
AU  - Koskela S
AD  - Finnish Red Cross Blood Service, Helsinki, Finland.
FAU - Hyvarinen, Kati
AU  - Hyvarinen K
AD  - Finnish Red Cross Blood Service, Helsinki, Finland.
FAU - FinnGen
AU  - FinnGen
AD  - Finnish Red Cross Blood Service, Helsinki, Finland.
FAU - Partanen, Jukka
AU  - Partanen J
AD  - Finnish Red Cross Blood Service, Helsinki, Finland. Electronic address: 
      jukka.partanen@bloodservice.fi.
LA  - eng
PT  - Journal Article
DEP - 20220224
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (HLA-DQ alpha-Chains)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (Histocompatibility Antigens Class I)
SB  - IM
MH  - Alleles
MH  - *Autoimmune Diseases/genetics
MH  - Finland
MH  - Gene Frequency
MH  - Genetic Predisposition to Disease
MH  - HLA-DQ alpha-Chains/genetics
MH  - HLA-DQ beta-Chains/genetics
MH  - HLA-DRB1 Chains/genetics
MH  - Haplotypes
MH  - *Histocompatibility Antigens Class I/genetics
MH  - Humans
OTO - NOTNLM
OT  - Biobank
OT  - Disease susceptibility
OT  - HLA
OT  - Pleiotropy
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2022/03/01 06:00
MHDA- 2022/04/27 06:00
CRDT- 2022/02/28 05:29
PHST- 2021/10/14 00:00 [received]
PHST- 2022/01/31 00:00 [revised]
PHST- 2022/02/09 00:00 [accepted]
PHST- 2022/03/01 06:00 [pubmed]
PHST- 2022/04/27 06:00 [medline]
PHST- 2022/02/28 05:29 [entrez]
AID - S0198-8859(22)00035-0 [pii]
AID - 10.1016/j.humimm.2022.02.003 [doi]
PST - ppublish
SO  - Hum Immunol. 2022 May;83(5):391-398. doi: 10.1016/j.humimm.2022.02.003. Epub 2022 
      Feb 24.