Abstract：
Genome-wide association study (GWAS) of Juvenile idiopathic arthritis (JIA) suffers from low power due to limited sample size and the interpretation challenge due to most signals located in non-coding regions. Gene-level analysis could alleviate these issues. Using GWAS summary statistics, we performed two typical gene-level analysis of JIA, transcriptome-wide association studies (TWAS) using FUnctional Summary-based ImputatiON (FUSION) and gene-based analysis using eQTL Multi-marker Analysis of GenoMic Annotation (eMAGMA), followed by comprehensive enrichment analysis. Among 33 overlapped significant genes from these two methods, 11 were previously reported, including TYK2 (PFUSION = 5.12 × 10-6, PeMAGMA = 1.94 × 10-7 for whole blood), IL-6R (PFUSION = 8.63 × 10-7, PeMAGMA = 2.74 × 10-6 for cells EBV-transformed lymphocytes), and Fas (PFUSION = 5.21 × 10-5, PeMAGMA = 1.08 × 10-6 for muscle skeletal). Some newly plausible JIA-associated genes are also reported, including IL-27 (PFUSION = 2.10 × 10-7, PeMAGMA = 3.93 × 10-8 for Liver), LAT (PFUSION = 1.53 × 10-4, PeMAGMA = 4.62 × 10-7 for Artery Aorta), and MAGI3 (PFUSION = 1.30 × 10-5, PeMAGMA = 1.73 × 10-7 for Muscle Skeletal). Enrichment analysis further highlighted 4 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and 10 Gene Ontology (GO) terms. Our findings can benefit the understanding of genetic determinants and potential therapeutic targets for JIA.
摘要：
幼年特发性关节炎（JIA）的全基因组关联研究（GWAS）由于样本量有限以及由于大多数信号位于非编码区而导致的解释挑战而遭受低功率。基因水平分析可以缓解这些问题。使用GWAS汇总统计，我们对JIA进行了两种典型的基因水平分析，使用FunctionalSummary-basedImputatiON（FUSION）的全转录组关联研究（TWAS）和使用基因注释的eQTL多标记分析（eMAGMA）的基于基因的分析，其次是综合富集分析。在这两种方法的33个重叠的重要基因中，以前有11个报道，包括TYK2（全血为PFUSION=5.12×10-6，PeMAGMA=1.94×10-7），IL-6R（PFUSION=8.63×10-7，PeMAGMA=2.74×10-6，用于EBV转化的淋巴细胞），和Fas（对于肌肉骨骼，PFUSION=5.21×10-5，PeMAGMA=1.08×10-6）。还报道了一些新的与JIA相关的基因，包括IL-27（对于肝脏，PFUSION=2.10×10-7，PeMAGMA=3.93×10-8），LAT（PFUSION=1.53×10-4，PeMAGMA=4.62×10-7，用于主动脉）和MAGI3（对于肌肉骨骼，PFUSION=1.30×10-5，PeMAGMA=1.73×10-7）。富集分析进一步强调了4个京都基因和基因组百科全书（KEGG）途径和10个基因本体论（GO）术语。我们的发现有助于理解JIA的遗传决定因素和潜在的治疗靶点。
