FRI0369 TOWARDS MORE PRECISE ESTIMATES OF THE FAMILIAL AGGREGATION AND HERITABILITY OF ANKYLOSING SPONDYLITIS – A SWEDISH NESTED CASE-CONTROL STUDY. (June 2019)

• Record Type: Journal Article
• Authors: Morin, Matilda; Hellgren, Karin; Frisell, Thomas
• Is Part Of: Annals of the rheumatic diseases. Volume 78(2019)Supplement 2
• Page Start: 866
• Page End: 867
• Publication Date: 2019-06
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2019-eular.1949
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Ankylosing spondylitis (AS) is known to have strong familial aggregation, but studies quantifying the familial risk are few and have reached varying results. Familial risks reported from population-based studies range from 17 to 94 in first-degree relatives of AS cases. 1 2 The heritability (i.e., the proportion of variance in AS liability explained by genetic variation) has been reported to >90%, based on very small studies of twins. 3 Objectives: To assess the familial aggregation and heritability of AS among all Swedish AS patients, and to investigate if risks vary by type of first-degree relative or sex. Methods: We identified all patients with an ICD-10 code of AS in the Swedish National Patient Register (NPR) between 1 January 2001 and 31 December 2016. To increase validity, index patients were required to have two or more visits listing an AS diagnosis, and at least one of the visits being to a specialist in rheumatology or internal medicine. Each index patient was matched on sex and birth year to 50 general population controls from the Total Population Register. First-degree relatives of index patients and controls were identified through the Multi-generation register. Their disease status was ascertained from the NPR in a similar manner as for index patients. Familial risks of AS among first-degree relatives were calculated as odds ratios (ORs) with conditional logistic regression. Based on the familial risks, the corresponding heritability was calculated for a range of plausible prevalence estimates. Results: We identified 13 795 patients that met the inclusion criteria. Of their siblings, parents, and children, 3.6, 2.3, and 2.1% respectively also had AS. The overall familial OR when having one affected relative was 19.4 (95% CI 18.1-20.8). The estimates were similar for relatives of different kinds (see table), but having more than one affected relative resulted in a higher risk (OR 68.0 (95% CI 51.3-90.1)). Heritability, estimated from sibling risk, was 77%. There were no clear-cut differences between the sexes, but women tended to have an elevated familial risk if the affected relative was female, and slightly lower heritability compared to males. These estimates can be considered as an upper limit of heritability, as shared environmental factors have not been taken into account in calculations. Conclusion: Familial risks of AS were similar between different types of first-degree relatives, and no significant gender difference was seen on the heritability scale. Although high compared to most other diseases, the familial risks and heritability were lower than previous reports from other countries, though in line with earlier Swedish findings using in part the same data source. The heritability proposed here might still be an overestimate of the true influence of genetics on disease risk. Thus, efforts should also be directed at identifying other risk factors for AS that are not of genetic origin. References: [1] Sundquist K, et al. Rheumatology2008;47(8):1199-202. [2] Geirsson AJ, Kristjansson K, Gudbjornsson B. Ann Rheum Dis2010;69(7):1346-8. [3] Brown MA, et al. Arthritis Rheum1997;40(10):1823-8. Disclosure of Interests: None declared