Institute of Clinical Molecular Biology, Christian-Albrechts-University, 24105 Kiel, Germany.
Am J Hum Genet. 2012 Apr 6;90(4):636-47. doi: 10.1016/j.ajhg.2012.02.020.
Psoriasis (PS) and Crohn disease (CD) have been shown to be epidemiologically, pathologically, and therapeutically connected, but little is known about their shared genetic causes. We performed meta-analyses of five published genome-wide association studies on PS (2,529 cases and 4,955 controls) and CD (2,142 cases and 5,505 controls), followed up 20 loci that showed strongest evidence for shared disease association and, furthermore, tested cross-disease associations for previously reported PS and CD risk alleles in additional 6,115 PS cases, 4,073 CD cases, and 10,100 controls. We identified seven susceptibility loci outside the human leukocyte antigen region (9p24 near JAK2, 10q22 at ZMIZ1, 11q13 near PRDX5, 16p13 near SOCS1, 17q21 at STAT3, 19p13 near FUT2, and 22q11 at YDJC) shared between PS and CD with genome-wide significance (p < 5 × 10(-8)) and confirmed four already established PS and CD risk loci (IL23R, IL12B, REL, and TYK2). Three of the shared loci are also genome-wide significantly associated with PS alone (10q22 at ZMIZ1, p(rs1250544) = 3.53 × 10(-8), 11q13 near PRDX5, p(rs694739) = 3.71 × 10(-09), 22q11 at YDJC, p(rs181359) = 8.02 × 10(-10)). In addition, we identified one susceptibility locus for CD (16p13 near SOCS1, p(rs4780355) = 4.99 × 10(-8)). Refinement of association signals identified shared genome-wide significant associations for exonic SNPs at 10q22 (ZMIZ1) and in silico expression quantitative trait locus analyses revealed that the associations at ZMIZ1 and near SOCS1 have a potential functional effect on gene expression. Our results show the usefulness of joint analyses of clinically distinct immune-mediated diseases and enlarge the map of shared genetic risk loci.
银屑病（PS）和克罗恩病（CD）在流行病学、病理学和治疗学上都有联系，但它们共同的遗传原因知之甚少。我们对五项已发表的 PS（2529 例病例和 4955 例对照）和 CD（2142 例病例和 5505 例对照）全基因组关联研究进行了荟萃分析，随后对 20 个显示最强疾病相关性的位点进行了随访，并且进一步在另外 6115 例 PS 病例、4073 例 CD 病例和 10100 例对照中检测了先前报道的 PS 和 CD 风险等位基因的交叉疾病关联。我们在人类白细胞抗原区域外鉴定出七个易感性位点（9p24 附近的 JAK2、10q22 处的 ZMIZ1、11q13 附近的 PRDX5、16p13 附近的 SOCS1、17q21 处的 STAT3、19p13 附近的 FUT2 和 22q11 处的 YDJC）在 PS 和 CD 之间具有全基因组意义上的显著相关性（p < 5×10(-8)），并证实了四个已建立的 PS 和 CD 风险位点（IL23R、IL12B、REL 和 TYK2）。三个共享的位点也与 PS 单独全基因组显著相关（10q22 处的 ZMIZ1，p(rs1250544) = 3.53×10(-8)，11q13 附近的 PRDX5，p(rs694739) = 3.71×10(-09)，22q11 处的 YDJC，p(rs181359) = 8.02×10(-10)）。此外，我们还鉴定出一个 CD 的易感位点（16p13 附近的 SOCS1，p(rs4780355) = 4.99×10(-8)）。对关联信号的细化分析确定了 10q22（ZMIZ1）处外显子 SNP 的全基因组显著关联和在 ZMIZ1 附近和 SOCS1 处的 SNP 与基因表达的潜在功能效应。我们的结果表明，对临床明显不同的免疫介导性疾病进行联合分析是有用的，并扩大了共同遗传风险位点的图谱。
