title: Fine-mapping in African-American women confirms the importance of the 10p12 locus to sarcoidosis.
abstract: 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 Women's Health Study. There were no significant associations with variants of the ANXA11 gene (P=0.17). Haplotypic analyses of the C10ORF67-OTUD1 intergenic region revealed a strong inverse association of the variants rs1398024 and rs11013452 with sarcoidosis (odds ratio=0.52; P=0.01). 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.
authors.affiliation: Slone Epidemiology Center at Boston University, Boston, MA 02215, USA. yvettec@bu.edu
authors.forename: Y C
authors.initials: YC
authors.lastname: Cozier
authors.forename: E A
authors.initials: EA
authors.lastname: Ruiz-Narvaez
authors.forename: C J
authors.initials: CJ
authors.lastname: McKinnon
authors.forename: J S
authors.initials: JS
authors.lastname: Berman
authors.forename: L
authors.initials: L
authors.lastname: Rosenberg
authors.forename: J R
authors.initials: JR
authors.lastname: Palmer
mesh_terms: D001741:Black or African American / Q000235:genetics; D017302:Annexins / Q000235:genetics; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D060148:HapMap Project; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D011995:Recombination, Genetic; D017565:Sarcoidosis, Pulmonary / Q000235:genetics*
chemical_list: D017302:Annexins