FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4379521275> ?p ?o ?g. }

• W4379521275 endingPage "128" @default.
• W4379521275 startingPage "128" @default.
• W4379521275 abstract "Background Juvenile idiopathic arthritis (JIA) encompasses a group of childhood onset rheumatic diseases that primarily affect females. JIA has been reported to occur in females and males with a 2:1 ratio, however, systemic JIA is reported to occur equally in sexes and enthesitis-related arthritis (ERA) is reported more frequently in male patients. Genetic risk factors may contribute to the sex dimorphism in JIA incidence, however this contribution has yet to be defined. Objectives To investigate, using sex dimorphism analysis, whether genetic risk factors for JIA differ in males and females. Methods High quality genotype data was available on 3356 JIA cases (females = 2209, males =1147) and 9196 controls (female =4059, males =5137). Our primary analysis combined sex-specific GWAS summary statistics using the GWAMA software package. Summary statistics were calculated using logistic regression with three principal components as covariates using PLINK. The sex-differentiated p-value (p diff ) provided overall evidence for association to JIA allowing for differences between males and females,and the heterogeneity p-value (p het ) provided evidence to support a difference in effect estimates between sexes. As a secondary analysis we performed a logistic regression, as above, on all samples and included sex as an interaction term (p int ). Amino acid residues in HLA genes and alleles were imputed using SNP2HLA and an association test with sex as an interaction term was implemented on markers of interest. Results A total of 6571296 SNPs were analysed after quality control. The strongest signal detected using a logistic regression in females was rs9469137 ( p = 1.7x10 -80 ) and in males it was rs116666910 ( p = 9.7x10 -59 ). GWAMA supported evidence of sex heterogeneity for these SNPs, rs9469137 p het = 2.2x10 -6 , OR males = 2.6, OR females = 5.3, rs116666910 p het = 1.8x10 -14 , OR male = 4.0, OR female = 1.6. The strongest signal from the sex-specific GWAS was rs9266716, p het = 1.9x10 -17 , p int = 7.7x10 -18 , OR male = 1.2, OR female = 0.6. These SNPs all map to the HLA region, providing strong evidence for sex dimorphism in this region, therefore sex-specific HLA fine mapping was conducted. This analysis revealed that residues at position 13 of HLA-DRB1 were strongly associated with JIA in females ( p female = 1.8x10 -124 ). Glycine at position 13 of HLA-DRB1 was most strongly associated with JIA in females (OR female = 3.6, p female = 4.1x10 -65 , OR male =1.9, p male = 9.6x10 -13 ). An association test with sex as an interaction term revealed glycine at position 13 as sex dimorphic, p = 4.3x10 -7 . Associations of residues at position 13 of HLA-DRB1 have previously been reported in JIA, where the cohort consisted of oligoarthritis and rheumatoid factor negative polyarthritis individuals. These ILAR subtypes have a greater frequency in females. HLA-B27 was detected as strongly associated with JIA in male patients ( p male =5.4 x10 -64 , OR male = 3.8, p female = 2.5x10 -9 , OR female = 1.6). An association test with sex as an interaction term revealed HLA-B27 to be strongly sex dimorphic, p = 7.5x10 -15 . HLA-B27 is a well-established risk factor for ERA, where males are predominately affected. Outside of the HLA region, the strongest associated SNP was rs58020114, p het = 6.3x10 -7 , p int = 5.7x10 -7 , OR male = 1.3, OR female =0.7. This SNP is located near the BPNT2 gene and had a greater effect size in males. Conclusion This analysis reveals that there are several sexually dimorphic genetic risk factors that may affect JIA development in males and females. For the first time markers within the HLA region have been detected as sex dimorphic. Understanding the genetic risk factors to JIA development will help to further define the disease, which may aid in disease classification and diagnosis in the future. In particular, the substantial differences in effect estimates observed between males and females suggests that sex-specific polygenic risk scores should be considered when HLA signals are incorporated into these efforts. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared." @default.
• W4379521275 created "2023-06-07" @default.
• W4379521275 creator A5020187396 @default.
• W4379521275 creator A5046887961 @default.
• W4379521275 creator A5068248314 @default.
• W4379521275 creator A5069396146 @default.
• W4379521275 creator A5077332816 @default.
• W4379521275 creator A5088575178 @default.
• W4379521275 date "2023-05-30" @default.
• W4379521275 modified "2023-09-27" @default.
• W4379521275 title "OP0193 SEX DIMORPHISM ANALYSIS IN A COHORT OF JIA PATIENTS REVEALS DIFFERING GENETIC RISK FACTORS FOR FEMALES AND MALES" @default.
• W4379521275 doi "https://doi.org/10.1136/annrheumdis-2023-eular.3537" @default.
• W4379521275 hasPublicationYear "2023" @default.
• W4379521275 type Work @default.
• W4379521275 citedByCount "0" @default.
• W4379521275 crossrefType "journal-article" @default.
• W4379521275 hasAuthorship W4379521275A5020187396 @default.
• W4379521275 hasAuthorship W4379521275A5046887961 @default.
• W4379521275 hasAuthorship W4379521275A5068248314 @default.
• W4379521275 hasAuthorship W4379521275A5069396146 @default.
• W4379521275 hasAuthorship W4379521275A5077332816 @default.
• W4379521275 hasAuthorship W4379521275A5088575178 @default.
• W4379521275 hasBestOaLocation W43795212751 @default.
• W4379521275 hasConcept C105083479 @default.
• W4379521275 hasConcept C120665830 @default.
• W4379521275 hasConcept C121332964 @default.
• W4379521275 hasConcept C126322002 @default.
• W4379521275 hasConcept C144024400 @default.
• W4379521275 hasConcept C149923435 @default.
• W4379521275 hasConcept C151956035 @default.
• W4379521275 hasConcept C2777077863 @default.
• W4379521275 hasConcept C61511704 @default.
• W4379521275 hasConcept C71924100 @default.
• W4379521275 hasConcept C72563966 @default.
• W4379521275 hasConceptScore W4379521275C105083479 @default.
• W4379521275 hasConceptScore W4379521275C120665830 @default.
• W4379521275 hasConceptScore W4379521275C121332964 @default.
• W4379521275 hasConceptScore W4379521275C126322002 @default.
• W4379521275 hasConceptScore W4379521275C144024400 @default.
• W4379521275 hasConceptScore W4379521275C149923435 @default.
• W4379521275 hasConceptScore W4379521275C151956035 @default.
• W4379521275 hasConceptScore W4379521275C2777077863 @default.
• W4379521275 hasConceptScore W4379521275C61511704 @default.
• W4379521275 hasConceptScore W4379521275C71924100 @default.
• W4379521275 hasConceptScore W4379521275C72563966 @default.
• W4379521275 hasIssue "Suppl 1" @default.
• W4379521275 hasLocation W43795212751 @default.
• W4379521275 hasOpenAccess W4379521275 @default.
• W4379521275 hasPrimaryLocation W43795212751 @default.
• W4379521275 hasRelatedWork W1580426574 @default.
• W4379521275 hasRelatedWork W1970383787 @default.
• W4379521275 hasRelatedWork W2275480158 @default.
• W4379521275 hasRelatedWork W2409957712 @default.
• W4379521275 hasRelatedWork W2603773853 @default.
• W4379521275 hasRelatedWork W2896226409 @default.
• W4379521275 hasRelatedWork W3095306390 @default.
• W4379521275 hasRelatedWork W4238089809 @default.
• W4379521275 hasRelatedWork W4241346791 @default.
• W4379521275 hasRelatedWork W4293581954 @default.
• W4379521275 hasVolume "82" @default.
• W4379521275 isParatext "false" @default.
• W4379521275 isRetracted "false" @default.
• W4379521275 workType "article" @default.