Genome-wide SNP association in psoriasis

描述（由申请人提供）：牛皮癣是一种常见的慢性炎症性皮肤病，影响约2%的欧洲人口。10-40%的时候伴有银屑病关节炎。牛皮癣是一种复杂的疾病，有许多易感变异和环境诱因。全面了解牛皮癣的遗传学对了解其发病机制非常重要，并且不太可能通过分析单个候选基因来揭示。一个主要的决定因素是HLA I类区域（PSORS1）内的一个位点，并且在全基因组连锁扫描后报道了超过19个非HLA位点。HLA内相关等位基因的外显率约为10%，人们认为这些非HLA等位基因的上位性是疾病发展所必需的。也可能有完全依赖hla的位点。连锁分析在确定银屑病易感性位点方面取得了有限的成功，而共同变异-共同疾病假说表明，全球基因组关联筛查在确定易感性变异方面可能要成功得多。我们打算利用高通量的全球筛选相关的snp，从HapMap项目中确定。来自Illumina Hap300K阵列的317,000个snp将在500例病例和匹配的欧洲血统对照中进行分型，之前对潜在的子结构进行了评估。将在1,000个新确定的病例和对照中进行3840个snp的后续研究。250个高度相关的snp将被分型到750个新确定的三人组中。5-15个潜在银屑病易感基因区域将成为疾病基因/变异鉴定的目标。一旦变异被确定，我们将在1250例/对照和1250例三人组中对其易感基因进行评估，这代表了我们收集的所有病例，无论种族如何。这将允许初步分析基因-基因和基因-环境的相互作用。

DESCRIPTION (provided by applicant): Psoriasis is a common, chronic inflammatory skin disease that affects approximately 2% of the N. European population. 10-40% of the time it is accompanied by psoriatic arthritis. Psoriasis is a complex disease with a number of predisposing variants and environmental triggers. A comprehensive understanding of the genetics of psoriasis is important for understanding its pathogenesis and is unlikely to be revealed by an analysis of single candidate genes. One major determinant is a locus within the HLA class I region (PSORS1) and over nineteen non-HLA loci have been reported following genome-wide linkage scans. The penetrance of associated alleles within HLA is ~10% and it is believed that epistasis with some of these non HLA alleles is required for disease development. There may also be loci that are entirely HLA-dependent. Linkage analyses have had limited success in identifying susceptibility loci for psoriasis, and the common variant-common disease hypothesis suggests that a global genome association screen may be far more successful at identifying susceptibility variants. We intend to exploit a high throughput global screen for associated SNPs, identified from the HapMap project. 317,000 SNPs from the Illumina Hap300K array will be typed in 500 cases and matched controls of European origin, previously evaluated for underlying substructure. Follow-up studies of 3840 SNPs will be performed in 1,000 newly ascertained cases and controls. 250 of the most highly associated SNPs will be typed in 750 newly ascertained trios. 5-15 regions harboring potential psoriasis susceptibility genes will be targeted for disease gene/variant identification. Once variants are identified they, and their predisposing genes will be evaluated in our complete set of >1250 cases/controls and 1250 trios, representative of all cases in our collection, regardless of ethnicity. This will permit a preliminary analysis of gene-gene and gene-environment interactions.