Methylation data from human retina samples profiled with Infinium HumanMethylationEPIC BeadChip. Methylation data from human retina samples profiled with Infinium HumanMethylationEPIC BeadChip

Age-related macular degeneration (AMD) is a complex multifactorial disease with at least 34 loci contributing to genetic susceptibility. To gain functional understanding of AMD genetics, we generated DNA methylation profiles of retina from 160 individuals including both controls and cases at distinct stages of AMD. With genotypes over 8 million common single nucleotide polymorphisms (SNPs) in cis, we identified 37,453 methylation quantitative trait loci (mQTL) and by integrating transcriptome of the same samples we identified 12,505 eQTLs and 13,747 DNAm sites that affect gene expression (eQTMs). We then integrated the AMD-genome-wide association studies (GWAS) data with mQTLs and eQTLs ascertained 87 target genes that may contribute to AMD risk. Our studies expand the methylation landscape of retina and AMD leading to direct targets for biological evaluation. Overall design: Genome wide DNA methylation profiling of human retina tissue samples from post-mortem donors. The Infinium HumanMethylationEPIC BeadChip was used to obtain DNA methylation profiles across approximately 850,000 CpGs sites from 160 tissue samples

年龄相关性黄斑变性（Age-related macular degeneration, AMD）是一种复杂的多因素疾病，至少有34个基因座参与其遗传易感性。为深入解析AMD遗传学的功能机制，我们对160名个体的视网膜组织开展DNA甲基化谱检测，样本覆盖AMD不同分期的病例组与健康对照组。依托顺式（cis）区域内超过800万个常见单核苷酸多态性（single nucleotide polymorphisms, SNPs）的基因型数据，我们共鉴定出37453个甲基化数量性状位点（methylation quantitative trait loci, mQTL）；通过整合同一样本的转录组数据，我们进一步鉴定出12505个表达数量性状位点（expression quantitative trait loci, eQTLs）与13747个影响基因表达的表达数量性状甲基化位点（expression quantitative trait methylation loci, eQTMs）。随后，我们将AMD全基因组关联研究（genome-wide association studies, GWAS）数据与mQTL、eQTL进行整合，最终确定了87个可能参与AMD发病风险调控的靶基因。本研究拓展了视网膜甲基化图谱与AMD相关研究的认知边界，为后续生物学验证提供了直接的候选靶标。
整体实验设计：本研究针对死后捐赠者的人类视网膜组织样本开展全基因组DNA甲基化谱分析，采用因菲宁人类甲基化EPIC微珠芯片（Infinium HumanMethylationEPIC BeadChip）对160份组织样本的约85万个CpG位点的甲基化水平进行检测。