Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan.
Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B), National Chiao Tung University, Hsinchu, Taiwan.
Sci Rep. 2021 Jan 12;11(1):478. doi: 10.1038/s41598-020-79515-4.
To determine whether genetic predisposition to endometriosis varies depending on ethnicity and in association with expression quantitative trait loci (eQTL) in a Taiwanese population. We conducted a genome-wide association study (GWAS) and replicated it in 259 individuals with laparoscopy-confirmed stage III or IV endometriosis (cases) and 171 women without endometriosis (controls). Their genomic DNA was extracted from blood and evaluated by the GWAS of Taiwan Biobank Array. Novel genetic variants that predispose individuals to endometriosis were identified using GWAS and replication, including rs10739199 (P = 6.75 × 10) and rs2025392 (P = 8.01 × 10) at chromosome 9, rs1998998 (P = 6.5 × 10) at chromosome 14, and rs6576560 (P = 9.7 × 10) at chromosome 15. After imputation, strong signals were exhibited by rs10822312 (P = 1.80 × 10) at chromosome 10, rs58991632 (P = 1.92 × 10) and rs2273422 (P = 2.42 × 10) at chromosome 20, and rs12566078 (P = 2.5 × 10) at chromosome 1. We used the Genotype-Tissue Expression (GTEx) database to observe eQTL. Among these SNPs, the cis-eQTL rs13126673 of inturned planar cell polarity protein (INTU) showed significant association with INTU expression (P = 5.1 × 10). Moreover, the eQTL analysis was performed on endometriotic tissues from women with endometriosis. The expression of INTU in 78 endometriotic tissue of women with endometriosis is associated with rs13126673 genotype (P = 0.034). To our knowledge, this is the first GWAS to link endometriosis and eQTL in a Taiwanese population.
为了确定遗传易感性是否因种族而异，并与台湾人群中的表达数量性状基因座（eQTL）相关联。我们进行了全基因组关联研究（GWAS），并在 259 名经腹腔镜确诊为 III 期或 IV 期子宫内膜异位症（病例）和 171 名无子宫内膜异位症的女性（对照组）中进行了复制。从血液中提取了他们的基因组 DNA，并通过台湾生物银行阵列进行了 GWAS 评估。使用 GWAS 和复制鉴定了导致个体易患子宫内膜异位症的新型遗传变异，包括染色体 9 上的 rs10739199（P=6.75×10）和 rs2025392（P=8.01×10），染色体 14 上的 rs1998998（P=6.5×10），和染色体 15 上的 rs6576560（P=9.7×10）。在进行了推测后，染色体 10 上的 rs10822312（P=1.80×10）、染色体 20 上的 rs58991632（P=1.92×10）和 rs2273422（P=2.42×10）以及染色体 1 上的 rs12566078（P=2.5×10）表现出强烈的信号。我们使用基因型组织表达（GTEx）数据库观察 eQTL。在这些 SNP 中，内翻平面细胞极性蛋白（INTU）的 cis-eQTL rs13126673 与 INTU 表达显著相关（P=5.1×10）。此外，还对子宫内膜异位症女性的子宫内膜异位组织进行了 eQTL 分析。78 名子宫内膜异位症女性的子宫内膜异位组织中 INTU 的表达与 rs13126673 基因型相关（P=0.034）。据我们所知，这是首次在台湾人群中进行子宫内膜异位症与 eQTL 相关联的 GWAS。
