Genetics and the axial spondyloarthritis spectrum

Brown, Matthew A.; Xu, Huji; Li, Zhixiu

doi:10.1093/rheumatology/keaa464

Cited by 22 publications

(23 citation statements)

References 83 publications

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“…As such, the question arises if these sex differences may present a novel insight into the pathogenesis of axSpA. The mechanic origin of enthesitis [ 23 , 24 ], sacroiliitis, and spondylitis [ 25 ] has been frequently discussed but the link between acute and chronic inflammation and mechanic stress on the one and immunpathology and the strong genetic influence represented by HLA-B27 and other genes [ 26 ] on the other side is incompletely understood. Based on the results presented here, the influence of HLA-B27 on BME in SIJ is different in males and females.…”

Section: Discussionmentioning

confidence: 99%

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Striking sex differences in magnetic resonance imaging findings in the sacroiliac joints in the population

et al. 2022

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Background In patients with axial spondyloarthritis (axSpA), magnetic resonance imaging (MRI) is used to detect bone marrow edema (BME) in sacroiliac joints (SIJ) but SIJ BME are also detected in the population. Not much is known about sex differences in that regard. Objective To explore sex-specific differences associated with the extent of BME in the SIJ suggestive of axSpA in a general population cohort study. Methods Taking advantage of 793 recently evaluated MRIs of subjects < 45 years taking part in the SHIP cohort, we used negative-binomial (NB) count data regression to analyze factors associated with the extent of SIJ BME. Predictors were explored by model-based boosting (MBB), a machine learning approach. Results Estimates of NB regression showed strong effects of sex in interaction with age, BMI, back pain, and particularly HLA-B27. The NB regression model showed incidence rate ratios (IRR) for the main effect of sex (females vs. males): 0.94 [95% CI: 0.63; 1.41], HLA-B27: 4.32 [2.09; 9.8], and for the interaction of sex to HLA-B27: 0.22 [0.06; 0.75]. According to MBB, HLA-B27 positivity, BMI, current smoking, back pain in the last 3 months, the interaction of sex and HLA-B27, and delivery in the last 12 months were of highest importance to explain the extent of SIJ BME. Conclusions Different factors were associated with the extent of SIJ BME in females and males. Most importantly, HLA-B27 was relevant only in males but not in females in whom a postpartal state was important. This finding may be relevant for the pathogenesis of axSpA.

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Section: Discussionmentioning

confidence: 99%

“…The gender with the lower prevalence requires a higher genetic risk before it develops the disease. Thus, overall, women with AS should have a higher genetic risk than men with the disease [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Striking sex differences in magnetic resonance imaging findings in the sacroiliac joints in the population

et al. 2022

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“…Traits implicated in our findings may represent candidates for patient classification, risk stratification and pain phenotyping in clinical management of chronic pain conditions. 21 Further, the proposition of a shared genetic signature underlying different types of regional chronic pain invites further investigation of genetic risk for chronic pain, 22,23 which may have potential applications for genetic stratification of patients in clinical trials, 24 to allow targeting of patients most at risk of developing chronic pain. Based on the precedent for genetically supported therapeutic targets, 2,3 traits with genetic causal effects identified in our study may represent potential treatment targets in management of chronic pain, providing convergent support for established approaches for treatment (e.g., weight-loss in knee osteoarthritis 25 ) or prevention of chronic pain (e.g., targeting post-traumatic stress after injury 26,27 ), as well as insight for development of emerging strategies (e.g., dietary 28 ).…”

Section: Discussionmentioning

confidence: 99%

A shared genetic signature for common chronic pain conditions and its impact on biopsychosocial traits

Farrell

Kho

Campos

et al. 2022

Preprint

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Background: The multifactorial heterogenous nature of chronic pain with its multiple comorbidities presents a formidable challenge in disentangling the aetiology underlying patient symptoms. Methods: Here, we performed genome-wide association studies (GWAS) of eight types of regional chronic pain using UK Biobank data (N=4,037-79,089 cases; N=239,125 controls), followed by bivariate linkage disequilibrium-score regression and latent causal variable analyses to determine (respectively) their genetic correlations and genetic causal proportion (GCP) parameters with 1,492 other complex traits. Findings: We report evidence of a shared genetic signature in common regional chronic pain types, with their genetic correlations and causal directions being broadly consistent across a wide array of biopsychosocial traits. Furthermore, we identified 5,942 significant genetic correlations, of which 570 trait pairs showed evidence of a likely causal association (|GCP| > 0.6; 5% false discovery rate), including 488 traits contributing to chronic pain while 82 were affected by pain. A range of somatic pathologies (e.g., musculoskeletal, visceral), psychiatric factors (e.g., depression, trauma, anxiety, mania, bipolar disorder), socioeconomic factors (e.g., occupation) and other medical comorbidities (e.g., cardiovascular disease) contributed to an increased risk of regional chronic pain. Conversely, each chronic pain type contributed to various other traits such as increased medication use (e.g., analgesics) and risk of ischaemic heart disease and depression. Interpretation: Findings of this data-driven study, through comprehensive analysis of a vast range of biopsychosocial factors, are indicative of a common genetic signature underlying eight regional chronic pain types. We identify a broad range of traits with genetic causal effects upon chronic pain, which may inform development of novel diagnostic and therapeutic strategies, as well as provide convergent support for various existing approaches.

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“…Axial SpA is clinically known to be a heterogeneous group of related disorders with similar clinical, genetic, pathological, and likely etiological features [ 28 ]. The group of conditions includes AS, psoriatic arthritis, reactive arthritis, and IBD-associated arthritis, according to the most prominent features of patients.…”

Section: Discussionmentioning

confidence: 99%

A cluster analysis of patients with axial spondyloarthritis using tumour necrosis factor alpha inhibitors based on clinical characteristics

et al. 2021

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Background This study aimed to classify the distinct group of patients with axial spondyloarthritis (SpA) on tumour necrosis factor alpha inhibitors (TNFi) according to the baseline characteristics using a clustering algorithm. Methods The clinical characteristics and demographic data of patients with axial SpA included in the Korean College of Rheumatology Biologics and Targeted Therapy registry were investigated. The patterns of disease manifestations were examined using divisive hierarchical cluster analysis. After clustering, we compared the clinical characteristics of patients and the drug survival of TNFi between the classified groups. Results A total of 1042 patients were analysed. The cluster analysis classified patients into two groups: axial group predominantly showing isolated axial manifestations (n = 828) and extra-axial group more frequently showing extra-axial symptoms (n = 214). Almost all extra-axial symptoms (peripheral arthritis, enthesitis, uveitis, and psoriasis) were more frequently observed in the extra-axial group than in the axial group. Moreover, patients in the extra-axial group had shorter disease duration, later disease onset, and higher disease activity than those in the axial group. The disease activity was comparable between the two groups after 1 year of treatment with TNFi. Interestingly, the extra-axial group had a lower drug survival with TNFi than the axial group (p = 0.001). Conclusions Cluster analysis of patients with axial SpA using TNFi classified two distinct clinical phenotypes. These clusters had different TNFi drug survival, clinical characteristics, and disease activity.

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Genetics and the axial spondyloarthritis spectrum

Cited by 22 publications

References 83 publications

Striking sex differences in magnetic resonance imaging findings in the sacroiliac joints in the population

Striking sex differences in magnetic resonance imaging findings in the sacroiliac joints in the population

A shared genetic signature for common chronic pain conditions and its impact on biopsychosocial traits

A cluster analysis of patients with axial spondyloarthritis using tumour necrosis factor alpha inhibitors based on clinical characteristics

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