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Familial aggregation and heritability of ankylosing spondylitis - a Swedish nested case-control study.

ABSTRACT: OBJECTIVES:AS is known to be a highly heritable disease, but previous studies on the magnitude of the familial aggregation and heritability of AS have been small and inconclusive, with familial relative risks ranging from 17 to 94. We aimed to improve estimates of these factors by studying families of all subjects diagnosed with AS in Sweden over a period of 16 years and to investigate if familial risks vary by sex or type of relative. METHODS:In a nested case-control study, we identified AS index patients from the National Patient Register (NPR) and the Swedish Rheumatology Quality Register (SRQ) between 2001 and 2016. Each index patient was matched on age and sex to up to 50 general population controls. First-degree relatives of index patients and controls were identified through the Multi-Generation Register, with disease status ascertained in the NPR and SRQ. Familial risks were defined as odds ratios (ORs) of having AS when exposed to a first-degree relative with AS, using conditional logistic regression. RESULTS:The overall familial OR for AS was 19.4 (95% CI 18.1, 20.8). Estimates were similar for different relative types and by sex, but having more than one affected relative resulted in a higher risk [OR 68.0 (95% CI 51.3, 90.1)]. Heritability, estimated by assuming sibling risks were completely due to genetics, was 77% (95% CI 73, 80). CONCLUSION:Although the familial risk and heritability of AS are higher than for most other diseases, we report estimates that are substantially lower than commonly referenced numbers for AS from other populations.

SUBMITTER: Morin M

PROVIDER: S-EPMC7310084 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Familial aggregation and heritability of ankylosing spondylitis - a Swedish nested case-control study.

Morin Matilda M Hellgren Karin K Frisell Thomas T

Rheumatology (Oxford, England) 20200701 7

<h4>Objectives</h4>AS is known to be a highly heritable disease, but previous studies on the magnitude of the familial aggregation and heritability of AS have been small and inconclusive, with familial relative risks ranging from 17 to 94. We aimed to improve estimates of these factors by studying families of all subjects diagnosed with AS in Sweden over a period of 16 years and to investigate if familial risks vary by sex or type of relative.<h4>Methods</h4>In a nested case-control study, we id ...[more]

PMID: 31687771

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Project description:BackgroundOutdoor air pollution has been found to trigger systemic inflammatory responses and aggravate the activity of certain rheumatic diseases. However, few studies have explored the influence of air pollution on the activity of ankylosing spondylitis (AS). As patients with active AS in Taiwan can be reimbursed through the National Health Insurance programme for biological therapy, we investigated the association between air pollutants and the initiation of reimbursed biologics for active AS.MethodsSince 2011, hourly concentrations of ambient air pollutants, including PM2.5, PM10, NO2, CO, SO2, and O3, have been estimated in Taiwan. Using Taiwanese National Health Insurance Research Database, we identified patients with newly diagnosed AS from 2003 to 2013. We selected 584 patients initiating biologics from 2012 to 2013 and 2336 gender-, age at biologic initiation-, year of AS diagnosis- and disease duration-matched controls. We examined the associations of biologics initiation with air pollutants exposure within 1 year prior to biologic use whilst adjusting for potential confounders, including disease duration, urbanisation level, monthly income, Charlson comorbidity index (CCI), uveitis, psoriasis and the use of medications for AS. Results are shown as adjusted odds ratio (aOR) with 95% confidence intervals (CIs).ResultsThe initiation of biologics was associated with exposure to CO (per 1 ppm) (aOR, 8.57; 95% CI, 2.02-36.32) and NO2 (per 10 ppb) (aOR, 0.23; 95% CI, 0.11-0.50). Other independent predictors included disease duration (incremental year, aOR, 8.95), CCI (aOR, 1.31), psoriasis (aOR, 25.19), use of non-steroidal anti-inflammatory drugs (aOR, 23.66), methotrexate use (aOR, 4.50; 95% CI, 2.93-7.00), sulfasalazine use (aOR, 12.16; 95% CI, 8.98-15.45) and prednisolone equivalent dosages (mg/day, aOR, 1.12).ConclusionsThis nationwide, population-based study revealed the initiation of reimbursed biologics was positively associated with CO levels, but negatively associated with NO2 levels. Major limitations included lack of information on individual smoking status and multicollinearity amongst air pollutants.

Project description:We have compared synovial biopsies from ankylosing spondylitis and undifferentiated spondylitis patients with healthy controls and osteoarthritis patients Objective: In spondylarthropies, whole-genome gene expression profiling studies have been limited to peripheral blood to date. By undertaking a study in knee synovial biopsies from spondylarthropy (SpA) and ankylosing spondylitis (AS) patients we aimed to identified joint-specific candidate genes and pathways. These pathways may mediate systemic inflammation driven joint damaging processes and more specifically, the osteoproliferation that is characteristic of these conditions. Methods: RNA was extracted from six seronegative SpA, two AS, three osteoarthritis (OA) and four normal control knee synovial biopsies. Whole genome expression profiling was undertaken using the Illumina DASL system, which assays 24000 cDNA probes. Differentially expressed candidate genes were then validated using quantitative PCR and immunohistochemistry. Results: 416 differentially expressed genes were identified that clearly delineated between AS/SpA and control groups. Pathway analysis showed altered gene-expression in oxidoreductase activity, osteoblast activity, B-cell associated, matrix catabolic, and metabolic pathways. The inflammatory mediator, MMP3, was strongly upregulated in AS/SpA samples and the Wnt pathway inhibitors DKK3 and Kremen1 were downregulated. Conclusion: Pathways mediating both systemic inflammation as well as local tissue changes were identified. This suggests initial systemic inflammation in spondylarthropies transfers to and persists in the local joint environment, subsequently mediating changes in genes directly involved in the destructive tissue remodelling. Fifteen knee synovial biopsy tissue samples consisting of six seronegative spondyloarthropy (SpA), two ankylosing spondylitis (AS), three osteoarthritis (OA) and four normal control biopsies were obtained from the Synovial Tissue Bank at the Repatriation General Hospital in Adelaide, South Australia with the appropriate ethical approval (Supplementary Table 1). All patients provided informed written consent.

Dataset Information

Familial aggregation and heritability of ankylosing spondylitis - a Swedish nested case-control study.

Publications

Familial aggregation and heritability of ankylosing spondylitis - a Swedish nested case-control study.

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