GWAS summary statistics of seven ADs were downloaded from Open Targets Genetics and Dryad. Linkage disequilibrium score regression (LDSC) was applied to estimate overall genetic correlations, bivariate causal mixture model (MiXeR) was used to qualify the polygenic overlap, and stratified-LDSC partitioned heritability to reveal tissue and cell type specific enrichments. Ultimately, we conducted a novel adaptive association test called MTaSPUsSet for identifying pleiotropic genes.
The high heritability of seven ADs ranged from 0.1228 to 0.5972, and strong genetic correlations among certain phenotypes varied between 0.185 and 0.721. There was substantial polygenic overlap, with the number of shared SNPs approximately 0.03K to 0.21K. The specificity of SNP heritability was enriched in the immune/hematopoietic related tissue and cells. Furthermore, we identified 32 pleiotropic genes associated with seven ADs, 23 genes were considered as novel genes. These genes were involved in several cell regulation pathways and immunologic signatures.
We comprehensively explored the shared genetic architecture across seven ADs. The findings progress the exploration of common molecular mechanisms and biological processes involved, and facilitate understanding of disease etiology.
■从OpenTargetsGeneticsandDryad下载了7个AD的GWAS汇总统计数据。连锁不平衡评分回归(LDSC)用于估计总体遗传相关性,双变量因果混合模型(MiXeR)用于鉴定多基因重叠,和分层LDSC分区的遗传力,以揭示组织和细胞类型特异性富集。最终,我们进行了一种名为MTaSPUsSet的新型适应性关联试验,用于鉴定多效性基因.
■七个AD的高遗传力范围为0.1228至0.5972,某些表型之间的强遗传相关性在0.185至0.721之间变化。有大量的多基因重叠,共享SNP的数量约为0.03K至0.21K。在免疫/造血相干组织和细胞中富集了SNP遗传力的特异性。此外,我们确定了32个与7个AD相关的多效性基因,23个基因被认为是新基因。这些基因参与几种细胞调节途径和免疫学特征。
■我们全面探索了七个AD的共享遗传结构。这些发现促进了对涉及的常见分子机制和生物过程的探索,并有助于了解疾病的病因。