PMID- 31487037
OWN - NLM
STAT- MEDLINE
DCOM- 20200526
LR  - 20201201
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Print)
IS  - 0009-9104 (Linking)
VI  - 198
IP  - 3
DP  - 2019 Dec
TI  - Pneumonia: host susceptibility and shared genetics with pulmonary function and 
      other traits.
PG  - 367-380
LID - 10.1111/cei.13367 [doi]
AB  - Pneumonia is a common and severe infectious lung disease. Host genetics, together 
      with underlying medical and lifestyle conditions, determine pneumonia 
      susceptibility. We performed a secondary analysis of the results of two 
      genome-wide studies for pneumonia in 23andMe participants (40 600 cases/90 039 
      controls) (Tian et al., 2017) and UK Biobank (BB) participants (12 614 
      cases/324 585 controls) (via the Global Biobank Engine) and used the GTEx 
      database to correlate the results with expression quantitative trait loci (eQTLs) 
      data in lung and whole blood. In the 23andMe pneumonia single nucleotide 
      polymorphism (SNP) set, 177 genotyped SNPs in the human leukocyte antigen (HLA) 
      region satisfied the genome-wide significance level, P </= 5.0E-08. Several target 
      genes (e.g. C4A, VARS2, SFTA2, HLA-C, HLA-DQA2) were unidirectionally regulated 
      by many HLA eSNPs associated with a higher risk of pneumonia. In lung, C4A 
      transcript was up-regulated by 291 pneumonia risk alleles spanning the half the 
      HLA region. Among SNPs correlated with the expression levels of SFTA2 and VARS2, 
      approximately 75% overlapped: all risk alleles were associated with VARS2 
      up-regulation and SFTA2 down-regulation. To find shared gene loci between 
      pneumonia and pulmonary function (PF), we used data from the Global Biobank 
      Engine and literature on genome-wide association studies (GWAS) of PF in general 
      populations. Numerous gene loci overlapped between pneumonia and PF: 28.8% in the 
      BB data set and 49.2% in the 23andMe data set. Enrichment analysis within the 
      database of Genotypes and Phenotypes (dbGaP) and National Human Genome Research 
      Institute-European Bioinformatics Institute (NHGRI-EBI) Catalog of pneumonia and 
      pneumonia/PF gene sets identified significant overlap between these gene sets and 
      genes related to inflammatory, developmental, neuropsychiatric and cardiovascular 
      and obesity-related traits.
CI  - (c) 2019 British Society for Immunology.
FAU - Khadzhieva, M B
AU  - Khadzhieva MB
AD  - Federal Research and Clinical Center of Intensive Care Medicine and 
      Rehabilitology, Moscow, Russia.
AD  - N. I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, 
      Russia.
AD  - Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and 
      Immunology, Moscow, Russia.
FAU - Kuzovlev, A N
AU  - Kuzovlev AN
AD  - Federal Research and Clinical Center of Intensive Care Medicine and 
      Rehabilitology, Moscow, Russia.
FAU - Salnikova, L E
AU  - Salnikova LE
AUID- ORCID: 0000-0002-9671-335X
AD  - Federal Research and Clinical Center of Intensive Care Medicine and 
      Rehabilitology, Moscow, Russia.
AD  - N. I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, 
      Russia.
AD  - Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and 
      Immunology, Moscow, Russia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191001
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (HLA Antigens)
RN  - 144515-61-7 (VARS2 protein, human)
RN  - EC 6.1.1.9 (Valine-tRNA Ligase)
SB  - IM
MH  - Adult
MH  - Gene Expression
MH  - Genetic Association Studies
MH  - Genetic Predisposition to Disease/*genetics
MH  - Genome-Wide Association Study/*methods
MH  - Genotype
MH  - HLA Antigens/genetics
MH  - Humans
MH  - Lung/*metabolism/pathology
MH  - Phenotype
MH  - Pneumonia/*genetics
MH  - *Polymorphism, Single Nucleotide
MH  - Quantitative Trait Loci/genetics
MH  - Valine-tRNA Ligase/genetics
PMC - PMC6857187
OTO - NOTNLM
OT  - C4A
OT  - eQTLs
OT  - genetic susceptibility
OT  - pneumonia
OT  - pulmonary function
COIS- The authors declare no competing financial interests.
EDAT- 2019/09/06 06:00
MHDA- 2020/05/27 06:00
PMCR- 2020/12/01
CRDT- 2019/09/06 06:00
PHST- 2019/08/29 00:00 [accepted]
PHST- 2019/09/06 06:00 [pubmed]
PHST- 2020/05/27 06:00 [medline]
PHST- 2019/09/06 06:00 [entrez]
PHST- 2020/12/01 00:00 [pmc-release]
AID - CEI13367 [pii]
AID - 10.1111/cei.13367 [doi]
PST - ppublish
SO  - Clin Exp Immunol. 2019 Dec;198(3):367-380. doi: 10.1111/cei.13367. Epub 2019 Oct 
      1.