Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America.
PLoS One. 2012;7(8):e43907. doi: 10.1371/journal.pone.0043907. Epub 2012 Aug 27.
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.
结节病是一种全身性炎症性疾病，其特征是受影响器官中肉芽肿的形成。对这种疾病的全基因组关联研究（GWAS）仅在欧洲人群中进行过。我们报告了首例在非裔美国人（818 例病例和 1088 名相关对照者）中进行的结节病 GWAS，随后在独立的非裔美国人群体（455 例病例和 557 名对照者）和欧洲裔美国人（442 例病例和 2284 名对照者）中进行了复制。我们评估了 >600 万个 SNP，这些 SNP 要么使用 Illumina Omni1-Quad 阵列进行基因分型，要么从 1000 基因组项目数据中进行推断。我们确定了一个新的结节病相关基因座 NOTCH4，该基因座在合并的 AA 样本中达到全基因组显著水平（rs715299，P(AA-meta) = 6.51 × 10(-10)），并证明了该基因座与同一样本中 MHC 区域内其他基因座的独立性。我们在我们的 AA 和 EA 数据集内复制了先前在 HLA-DRA、HLA-DRB5、HLA-DRB1、BTNL2 和 ANXA11 中进行的欧洲 GWAS 关联。我们还确认了在 EA 但不是 AA 样本中与先前报道的 HLA-C 和 HLA-B 区域的显著关联。我们还进一步确定了与先前在肺部或炎症性疾病中报道的其他几个基因的提示性关联。
