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Familial aggregation and heritability of sarcoidosis: a Swedish nested case-control study.
European Respiratory Journal 2018 August
Sarcoidosis is believed to be caused by both genetic and environmental risk factors, but the proportion of the susceptibility to sarcoidosis that is mediated by genetics remains unknown. We aimed to estimate the familial aggregation and heritability of sarcoidosis using a case-control-family study design and population-based Swedish registers.We identified 23 880 individuals with visits for sarcoidosis in the Swedish National Patient Register using International Classification of Diseases codes (1964‒2013). Information on Löfgren's syndrome was available for a subset diagnosed at Karolinska University Hospital (Stockholm, Sweden). General population controls were matched to cases (10:1). Relatives of cases and controls were identified from the Swedish Multi-Generation Register and ascertained for sarcoidosis in the National Patient Register. We estimated familial relative risks for sarcoidosis using conditional logistic regression and heritability using biometric models.Having at least one first-degree relative with sarcoidosis was associated with a 3.7-fold increase in the risk of sarcoidosis (95% CI 3.4-4.1). The relative risk increased in those with two or more relatives (relative risk 4.7) and in Löfgren's syndrome (relative risk 4.1). The heritability was 39% (95% CI 12-65%).This large investigation showed that having a relative with sarcoidosis is a very strong risk factor for the disease. Genetic variation is an important, albeit partial, contributing factor to the risk for sarcoidosis.
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