Fine-mapping in African Americans women confirms the importance of the 10p12 locus to sarcoidosis

Sarcoidosis is a chronic granulomatous disease with a wide spectrum of symptoms. Genome-wide association studies in European populations have reported significant associations between sarcoidosis and single nucleotide polymorphisms (SNPs) located in the inter-genic region between the C10ORF67 and OTUD1 genes on chromosome 10p12, and the ANXA11 gene (chromosome 10q22). We carried out fine-mapping at 10p12 and 10q22 to assess associations of genetic variants in those regions with sarcoidosis risk in African American women, based on 486 sarcoidosis cases and 943 age- and geography-matched controls in a nested case-control study within the Black Women’s Health Study. There were no significant associations with variants of the ANXA11 gene (P=0.17). Haplotypic analyses of the C10ORF67-OTUD1 inter-genic region revealed a strong inverse association of the variants rs1398024 and rs11013452 with sarcoidosis (OR=0.52; P=0.01). Both SNPs are located inside a ~300 kb low recombination region of chromosome 10p12, suggesting that both SNPs are tagging the same causal variant. Our top SNP (rs11013452) is located inside a smaller LD block in HapMap YRI, further narrowing the position of the causal SNP to a region of ~ 8kb on chromosome 10p12. The present findings confirm the potential importance of the 10p12 locus in the etiology of sarcoidosis.