Introduction: Sarcoidosis is a disease that usually affects the lungs and lymph nodes, but the clinical manifestations and course of the disease vary. The disease in young patients is typically self-limiting and spontaneously resolving, while multi-organ manifestations and a persisting course of the disease are more common in elderly patients. The genomics of sarcoidosis patients of different ages have not been previously compared.

Objectives: Our objective was to investigate whether the genetic architecture associated with sarcoidosis varies between individuals who develop the disease at different ages.

Materials and Methods: Patients with a sarcoidosis endpoint in the FinnGen cohort (n = 5,576) were identified and stratified into age groups. We performed a genome-wide association study (GWAS) and examined human leukocyte antigen (HLA) alleles associated with sarcoidosis across the different age categories. Additionally, we compared the effect sizes of the identified risk alleles between the age groups.

Results: Sarcoidosis was diagnosed at the age of ≤40 years in 1918 patients (943 men, 975 women, mean age 31.9 years) and at later age in 3813 cases (1579 men, 2234 women, mean age 55.7 years). Thirteen risk loci reached genome-wide significance (p < 5 × 10⁻⁸) among young patients and 9 loci among the elderly. Effect size differences between the age groups were observed in HLA region and in the alleles IGKC, IL21R and DHRS7C. IGKC, IL21R and eight HLA alleles increased the risk of sarcoidosis at age ≤40 years but had a smaller effect on risk in the elderly (Figure 1). DHRS7C and three HLA alleles increased disease risk in patients >40 years but had less effect on risk at a younger age.

Conclusions: Our results reveal distinct risk alleles for sarcoidosis across different age groups, providing new insights into the disease’s pathology.