{"id":245,"title":"Single-Cell Immune Cis-eQTL Mendelian Randomization Prioritizes Cell-Type-Resolved Candidate Causal Genes for Endometriosis","title_zh":"单细胞免疫 cis-eQTL 孟德尔随机化优先筛选子宫内膜异位症的细胞类型特异性候选因果基因","url":"https://pubmed.ncbi.nlm.nih.gov/42979209","doi":"10.2147/ijwh.s643362","pmid":"42979209","journal":"Int J Womens Health","kind":"paper","lang":"en","published_at":"2026-10-30T00:00:00+00:00","fetched_at":"2026-11-08T03:44:00+00:00","authors":["Wang X","Yao G","Ding W"],"primary_topic":"endometrium","topics":[{"slug":"endometrium","score":4.0,"hits":["endometriosis"]},{"slug":"omics-methods","score":4.0,"hits":["single-cell"]}],"topic_score":4.0,"preference_score":0.0,"preference_labels":[],"llm_score":71.0,"final_score":71.0,"score_dims":{"novelty":76,"rigor":72,"impact":66,"relevance":62,"translation":55},"recommend_reason":"将单细胞 eQTL 与孟德尔随机化、共定位整合到细胞类型层面，为子宫内膜异位症的免疫遗传机制提供可检验的候选基因清单；方法框架对生殖遗传与多组学研究者有借鉴价值，但结论仍属探索性、缺乏实验验证与临床可用性。","keywords":["子宫内膜异位症","单细胞eQTL","孟德尔随机化","共定位分析","免疫细胞类型","IGF1R"],"selected":1,"story_id":269,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-uterus-pregnancy","source_name":"PubMed · 内膜/植入/早孕","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":null,"journal_tier":"unknown","journal_if":null,"is_mock":false,"summary_zh":"研究利用 OneK1K 中 20 种外周血免疫细胞类型的单细胞 cis-eQTL 工具变量，对 FinnGen R12 子宫内膜异位症（20,190 例病例、130,160 例对照）开展单变异孟德尔随机化，并结合共定位与敏感性分析。在 9157 个基因-细胞类型检验中，61 个基因的 135 个关联达到 BH-FDR<0.05；默认先验下的共定位优先得到 10 个基因（6 个蛋白编码），其中 LOC102723878 与 RUVBL1 同时经 BY 校正稳健，NK 细胞 IGF1R 仅为探索性提示（PP4=0.89，OR 1.11/SD），病灶表达趋势不显著（P=0.101）。作者强调结果为功能研究提供免疫语境候选基因，不构成治疗或生殖安全性证据。","summary":"BACKGROUND: Endometriosis has a substantial immune component, but the cellular contexts of genetically regulated disease susceptibility remain incompletely resolved. METHODS: We tested single-cell cis-eQTL instruments from 20 OneK1K peripheral-blood cell types against FinnGen R12 endometriosis (20,190 cases; 130,160 controls) using single-variant Mendelian randomization (MR), colocalization and sensitivity analyses. Benjamini-Yekutieli (BY) correction distinguished conservative findings from an exploratory Benjamini-Hochberg (BH) screen. Directional consistency, bulk-blood MR and lesion expression provided contextual comparisons. RESULTS: Across 9157 unique gene-cell-type tests, 135 associations in 61 genes reached BH-FDR < 0.05. Colocalization at the default prior prioritized 10 genes (6 protein-coding) across 28 pairs. LOC102723878 and RUVBL1 were also BY-robust; IGF1R in natural killer (NK) cells was BH-supported but not BY-robust (PP4 = 0.89; OR 1.11 per SD higher expression). Its NK attribution reflects instrument availability and does not establish exclusivity. Colocalization was prior-sensitive. Directional concordance in a partly overlapping sample (8/8) was descriptive. Bulk-blood MR nominated 3/6 testable protein-coding genes. IGF1R lesion expression showed a nonsignificant upward trend (P = 0.101). CONCLUSION: The analysis prioritizes immune-context candidate genes for functional study. IGF1R remains an exploratory, mechanistically unresolved nomination. Genetic support and protein tractability do not establish therapeutic benefit or reproductive safety; experimental validation is required.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}