According to study results published in Rheumatology, although heritability and familial risk for ankylosing spondylitis (AS) in a Swedish cohort were high, risk estimates were lower than those reported for cohorts in other countries.
Using data from Swedish national registers, researchers conducted a nested case-control study to determine accurate estimates of familial aggregation and heritability of AS. They identified data of index patients from the National Patient Register and the Swedish Rheumatology Quality Register and matched each patient 5:1 for sex and age with randomly selected general population control participants.
In total, the investigators collected data of 14,240 unique index patients with an AS diagnosis and ≥2 specialist visits from across both registers. After excluding participants with missing demographic data, they included 13,795 index patients and 668,936 healthy controls in the study.
Of the relatives identified by the Multi-Generation Register, investigators found that the percentage of affected relatives was similar for index patients from the Swedish Rheumatology Quality Register alone and from the National Patient Register and the Swedish Rheumatology Quality Register together. Patients in the index group had a higher percentage of affected relatives compared with the control group, across all types of relatives (11.1% vs 0.6%, respectively); mean number of relatives did not differ significantly between the index and control groups.
Overall, the odds ratio (OR) for AS in patients with an affected relative was 19.4 (95% CI, 18.1-20.8). These estimates were similar for exposure from different types of relatives; however, having more than 1 affected relative resulted in a considerably higher risk (OR, 68.0; 95% CI, 51.3-90.1). When estimated from sibling risks, heritability was 77% (95% CI, 73%-80%), which assumed a prevalence of 0.11%. Heritability varied from 72% to 82% (95% CI, 69%-75% and 78%-86%, respectively) depending on the prevalence used (0.055%-0.22%).
According to the researchers, women had an elevated familial risk in cases where the affected relative was a woman; however, since the prevalence of AS in women was lower, they had similar or slightly lower heritability compared with men. Investigators observed increased familial risk only for mother-daughter pairs; sisters and brothers had the same familial risk.
When stratified by age at disease onset, investigators noted a trend toward increased familial risk in patients who had disease onset before the age of 25 years compared with those with disease onset after the age of 25 years. This trend was consistent for all types of relatives.
Study limitations included the inability to validate each diagnosis because of the use of register data, potential underestimation of AS in older relatives, and lack of data on patient risk-allele human leukocyte antigen-B27 status.
“We found that while familial risks and heritability of AS were very high, they were lower than previous reports from other countries,” the researchers concluded. “From a clinical perspective, this strong familiality should motivate further research to evaluate if and how knowledge about a family history of AS may help to predict disease activity, prognosis, and treatment outcomes.”
Morin M, Hellgren K, Frisell T. Familial aggregation and heritability of ankylosing spondylitis — a Swedish nested case-control study [published online November 5, 2019]. Rheumatology. doi:10.1093/rheumatology/kez519