Fine-mapping in African-American 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 intergenic 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 these 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 Womens Health Study. There were no significant associations with variants of the ANXA11 gene (P0.17). Haplotypic analyses of the C10ORF67-OTUD1 intergenic region revealed a strong inverse association of the variants rs1398024 and rs11013452 with sarcoidosis (odds ratio0.52; P0.01). Both SNPs are located inside an 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 linkage disequilibrium block in HapMap YRI, further narrowing the position of the causal SNP to a region of 8 kb on chromosome 10p12. The present findings confirm the potential importance of the 10p12 locus in the etiology of sarcoidosis. © 2012 Macmillan Publishers Limited. All rights reserved.

Publication Title

Genes and Immunity