Genome-wide association study of African and European Americans implicates multiple shared and ethnic specific loci in sarcoidosis susceptibility

• Published in: PloS one 2012-08, Vol.7 (8), p.e43907
• Main Authors: Adrianto, Indra, Lin, Chee Paul, Hale, Jessica J, Levin, Albert M, Datta, Indrani, Parker, Ryan, Adler, Adam, Kelly, Jennifer A, Kaufman, Kenneth M, Lessard, Christopher J, Moser, Kathy L, Kimberly, Robert P, Harley, John B, Iannuzzi, Michael C, Rybicki, Benjamin A, Montgomery, Courtney G
• Format: Article
• Language: English
• Subjects: Arthritis; Bioinformatics; Biology; Black or African American - genetics; Databases, Genetic; Datasets; Disease; Drb1 protein; Ethnicity; Female; Gene expression; Genetic Loci - genetics; Genetic Predisposition to Disease - ethnology; Genetic Predisposition to Disease - genetics; Genome-wide association studies; Genome-Wide Association Study; Genomes; Health sciences; Histocompatibility antigen HLA; Humans; Immunology; Inflammatory diseases; Loci; Lung diseases; Major histocompatibility complex; Major Histocompatibility Complex - genetics; Male; Medical research; Meta-analysis; Meta-Analysis as Topic; Minority & ethnic groups; Organs; Pedigree; Population; Principal components analysis; Prostate; Public health; Reproducibility of Results; Rheumatology; Sarcoidosis; Sarcoidosis - genetics; Single-nucleotide polymorphism; Studies; White People - genetics
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0043907

Sarcoidosis is a systemic inflammatory disease characterized by the formation of granulomas in affected organs. Genome-wide association studies (GWASs) of this disease have been conducted only in European population. We present the first sarcoidosis GWAS in African Americans (AAs, 818 cases and 1,088 related controls) followed by replication in independent sets of AAs (455 cases and 557 controls) and European Americans (EAs, 442 cases and 2,284 controls). We evaluated >6 million SNPs either genotyped using the Illumina Omni1-Quad array or imputed from the 1000 Genomes Project data. We identified a novel sarcoidosis-associated locus, NOTCH4, that reached genome-wide significance in the combined AA samples (rs715299, P(AA-meta) = 6.51 × 10(-10)) and demonstrated the independence of this locus from others in the MHC region in the same sample. We replicated previous European GWAS associations within HLA-DRA, HLA-DRB5, HLA-DRB1, BTNL2, and ANXA11 in both our AA and EA datasets. We also confirmed significant associations to the previously reported HLA-C and HLA-B regions in the EA but not AA samples. We further identified suggestive associations with several other genes previously reported in lung or inflammatory diseases.