PMID- 34101054
OWN - NLM
STAT- MEDLINE
DCOM- 20210928
LR  - 20220218
IS  - 1434-9949 (Electronic)
IS  - 0770-3198 (Print)
IS  - 0770-3198 (Linking)
VI  - 40
IP  - 10
DP  - 2021 Oct
TI  - Association analysis of juvenile idiopathic arthritis genetic susceptibility 
      factors in Estonian patients.
PG  - 4157-4165
LID - 10.1007/s10067-021-05756-x [doi]
AB  - BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common chronic 
      rheumatic condition of childhood. Genetic association studies have revealed 
      several JIA susceptibility loci with the strongest effect size observed in the 
      human leukocyte antigen (HLA) region. Genome-wide association studies have 
      augmented the number of JIA-associated loci, particularly for non-HLA genes. The 
      aim of this study was to identify new associations at non-HLA loci predisposing 
      to the risk of JIA development in Estonian patients. METHODS: We performed 
      genome-wide association analyses in an entire JIA case-control sample (All-JIA) 
      and in a case-control sample for oligoarticular JIA, the most prevalent JIA 
      subtype. The entire cohort was genotyped using the Illumina HumanOmniExpress 
      BeadChip arrays. After imputation, 16,583,468 variants were analyzed in 263 cases 
      and 6956 controls. RESULTS: We demonstrated nominal evidence of association for 
      12 novel non-HLA loci not previously implicated in JIA predisposition. We 
      replicated known JIA associations in CLEC16A and VCTN1 regions in the 
      oligoarticular JIA sample. The strongest associations in the All-JIA analysis 
      were identified at PRKG1 (P = 2,54 x 10(-6)), LTBP1 (P = 9,45 x 10(-6)), and 
      ELMO1 (P = 1,05 x 10(-5)). In the oligoarticular JIA analysis, the strongest 
      associations were identified at NFIA (P = 5,05 x 10(-6)), LTBP1 
      (P = 9,95 x 10(-6)), MX1 (P = 1,65 x 10(-5)), and CD200R1 (P = 2,59 x 10(-5)). 
      CONCLUSION: This study increases the number of known JIA risk loci and provides 
      additional evidence for the existence of overlapping genetic risk loci between 
      JIA and other autoimmune diseases, particularly rheumatoid arthritis. The 
      reported loci are involved in molecular pathways of immunological relevance and 
      likely represent genomic regions that confer susceptibility to JIA in Estonian 
      patients. Key Points * Juvenile idiopathic arthritis (JIA) is the most common 
      childhood rheumatic disease with heterogeneous presentation and genetic 
      predisposition. * Present genome-wide association study for Estonian JIA patients 
      is first of its kind in Northern and Northeastern Europe. * The results of the 
      present study increase the knowledge about JIA risk loci replicating some 
      previously described associations, so adding weight to their relevance and 
      describing novel loci. * The study provides additional evidence for the existence 
      of overlapping genetic risk loci between JIA and other autoimmune diseases, 
      particularly rheumatoid arthritis.
CI  - (c) 2021. The Author(s).
FAU - Nikopensius, Tiit
AU  - Nikopensius T
AD  - Estonian Genome Center, Institute of Genomics, University of Tartu, Riia 23B, 
      51010, Tartu, Estonia. tiitn@ut.ee.
FAU - Niibo, Priit
AU  - Niibo P
AUID- ORCID: 0000-0001-5223-9054
AD  - Institute of Dentistry, University of Tartu, Tartu, Estonia.
FAU - Haller, Toomas
AU  - Haller T
AD  - Estonian Genome Center, Institute of Genomics, University of Tartu, Riia 23B, 
      51010, Tartu, Estonia.
FAU - Jagomagi, Triin
AU  - Jagomagi T
AD  - Institute of Dentistry, University of Tartu, Tartu, Estonia.
FAU - Voog-Oras, Ulle
AU  - Voog-Oras U
AD  - Institute of Dentistry, University of Tartu, Tartu, Estonia.
AD  - Stomatology Clinic, Tartu University Hospital, Tartu, Estonia.
FAU - Tonisson, Neeme
AU  - Tonisson N
AD  - Estonian Genome Center, Institute of Genomics, University of Tartu, Riia 23B, 
      51010, Tartu, Estonia.
AD  - Department of Clinical Genetics, United Laboratories, Tartu University Hospital, 
      Tartu, Estonia.
FAU - Metspalu, Andres
AU  - Metspalu A
AD  - Estonian Genome Center, Institute of Genomics, University of Tartu, Riia 23B, 
      51010, Tartu, Estonia.
FAU - Saag, Mare
AU  - Saag M
AD  - Institute of Dentistry, University of Tartu, Tartu, Estonia.
FAU - Pruunsild, Chris
AU  - Pruunsild C
AD  - Children's Clinic, Tartu University Hospital, Tartu, Estonia.
AD  - Children's Clinic, Institute of Clinical Medicine, Faculty of Medicine, 
      University of Tartu, Tartu, Estonia.
LA  - eng
GR  - ETF9255/Estonian Science Foundation/
PT  - Journal Article
DEP - 20210608
PL  - Germany
TA  - Clin Rheumatol
JT  - Clinical rheumatology
JID - 8211469
SB  - IM
MH  - *Arthritis, Juvenile/genetics
MH  - Case-Control Studies
MH  - Estonia
MH  - *Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - Humans
MH  - Polymorphism, Single Nucleotide
PMC - PMC8463396
OTO - NOTNLM
OT  - Genome-wide association study
OT  - Juvenile idiopathic arthritis
OT  - Rheumatoid arthritis
EDAT- 2021/06/09 06:00
MHDA- 2021/09/29 06:00
PMCR- 2021/06/08
CRDT- 2021/06/08 12:30
PHST- 2021/01/17 00:00 [received]
PHST- 2021/04/27 00:00 [accepted]
PHST- 2021/04/26 00:00 [revised]
PHST- 2021/06/09 06:00 [pubmed]
PHST- 2021/09/29 06:00 [medline]
PHST- 2021/06/08 12:30 [entrez]
PHST- 2021/06/08 00:00 [pmc-release]
AID - 10.1007/s10067-021-05756-x [pii]
AID - 5756 [pii]
AID - 10.1007/s10067-021-05756-x [doi]
PST - ppublish
SO  - Clin Rheumatol. 2021 Oct;40(10):4157-4165. doi: 10.1007/s10067-021-05756-x. Epub 
      2021 Jun 8.