Dissecting genetic components associated with eye disease using integrative genomic analysis [ATAC-seq]

GWAS studies have revealed thousands of variants strongly associated with AMD, yet connecting these variants to their cognate genes has not been explored. In this study we fine-mapped AMD risk loci and examined long-range cis chromatin interactions at essential genes of RPE function and disease-associated variants in iPSC-induced retinal pigmented epithelium (RPE) and primary RPE. Overall design: ATAC-seq from iPSCs (2 replicates), iPSC-induced RPE (3 replicates) and primary RPE (3 replicates)全基因组关联研究（Genome-Wide Association Study, GWAS）已揭示数千个与年龄相关性黄斑变性（Age-Related Macular Degeneration, AMD）显著相关的遗传变异，但目前尚未开展将这些变异与其对应基因建立关联的相关工作。 本研究对AMD风险位点进行了精细定位，并在诱导多能干细胞（induced pluripotent stem cell, iPSC）诱导生成的视网膜色素上皮（retinal pigmented epithelium, RPE）以及原代RPE细胞中，针对RPE功能相关关键基因与疾病关联变异开展了长距离顺式染色质相互作用分析。 实验设计概况：本研究对iPSCs（2个生物学重复）、iPSC诱导的RPE（3个生物学重复）以及原代RPE（3个生物学重复）样本开展了转座酶可及性测序（Assay for Transposase-Accessible Chromatin using sequencing, ATAC-seq）实验。