Department of Nephrology, Huashan Hospital, Fudan University, 12 Middle Wurumuqi Road, Jingan District, Shanghai, 200040, China.
Wuhu Hospital of Traditional Chinese Medicine, Anhui College of Traditional Chinese Medicine, Wuhu, Anhui, China.
BMC Med Genomics. 2023 Jan 29;16(1):16. doi: 10.1186/s12920-023-01436-8.
Immunoglobulin A nephropathy (IgAN) is a complex autoimmune disease, and the exact pathogenesis remains to be elucidated. This study aimed to explore genes underlying the pathogenesis of IgAN.
We conducted the summary data-based Mendelian randomization (SMR) analysis and performed functional mapping and annotation using FUMA to explore genetic loci that are potentially involved in the pathogenies of IgAN. Both analyses used summarized data of a recent genome-wide association study (GWAS) on IgANs, which included 477,784 Europeans (15,587 cases and 462,197 controls) and 175,359 East Asians (71 cases and 175,288 controls). We performed SMR analysis using Consortium for the Architecture of Gene Expression (CAGE) expression quantitative trait loci (eQTL) data and replicated the analysis using Genotype-Tissue Expression (GTEx) eQTL data.
Using the CAGE eQTL data, our SMR analysis identified 32 probes tagging 25 unique genes whose expression were pleiotropically associated with IgAN, with the top three probes being ILMN_2150787 (tagging HLA-C, P= 2.10 × 10), ILMN_1682717 (tagging IER3, P= 1.07 × 10) and ILMN_1661439 (tagging FLOT1, P=1.16 × 10). Using GTEx eQTL data, our SMR analysis identified 24 probes tagging 24 unique genes whose expressions were pleiotropically associated with IgAN, with the top three probes being ENSG00000271581.1 (tagging XXbac-BPG248L24.12, P= 1.44 × 10), ENSG00000186470.9 (tagging BTN3A2, P= 2.28 × 10), and ENSG00000224389.4 (tagging C4B, P= 1.23 × 10 ). FUMA analysis identified 3 independent, significant and lead SNPs, 2 genomic risk loci and 39 genes that are potentially involved in the pathogenesis of IgAN.
We identified many genetic variants/loci that are potentially involved in the pathogenesis of IgAN. More studies are needed to elucidate the exact mechanisms of the identified genetic variants/loci in the etiology of IgAN.
免疫球蛋白 A 肾病（IgAN）是一种复杂的自身免疫性疾病，其确切的发病机制仍有待阐明。本研究旨在探讨 IgAN 发病机制相关的基因。
我们进行了基于汇总数据的孟德尔随机化（SMR）分析，并使用 FUMA 进行功能映射和注释，以探索可能与 IgAN 发病机制相关的遗传位点。这两种分析均使用最近的 IgAN 全基因组关联研究（GWAS）的汇总数据进行，该研究包括 477784 名欧洲人（15587 例病例和 462197 名对照）和 175359 名东亚人（71 例病例和 175288 名对照）。我们使用联盟基因表达结构（CAGE）表达定量性状基因座（eQTL）数据进行 SMR 分析，并使用基因型组织表达（GTEx）eQTL 数据复制分析。
使用 CAGE eQTL 数据，我们的 SMR 分析确定了 32 个探针标记了 25 个独特的基因，这些基因的表达与 IgAN 存在多效关联，前三个探针分别是 ILMN_2150787（标记 HLA-C，P=2.10×10）、ILMN_1682717（标记 IER3，P=1.07×10）和 ILMN_1661439（标记 FLOT1，P=1.16×10）。使用 GTEx eQTL 数据，我们的 SMR 分析确定了 24 个探针标记了 24 个独特的基因，这些基因的表达与 IgAN 存在多效关联，前三个探针分别是 ENSG00000271581.1（标记 XXbac-BPG248L24.12，P=1.44×10）、ENSG00000186470.9（标记 BTN3A2，P=2.28×10）和 ENSG00000224389.4（标记 C4B，P=1.23×10）。FUMA 分析确定了 3 个独立的、显著的和主要的 SNP、2 个基因组风险位点和 39 个可能参与 IgAN 发病机制的基因。
我们确定了许多遗传变异/位点，这些变异/位点可能与 IgAN 的发病机制有关。需要进一步研究以阐明这些遗传变异/位点在 IgAN 病因学中的确切机制。
