Cheng Yuan-Fang, Yang Cheng-Yi, Tsai Meng-Che
School of Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
Department of Statistics, College of Management, National Cheng Kung University, Tainan 70101, Taiwan.
Biomedicines. 2024 Jan 11;12(1):157. doi: 10.3390/biomedicines12010157.
Age at menarche (AAM) has been associated with type 2 diabetes mellitus (T2DM). However, little is known about their shared heritability. Our data comes from the Taiwan Biobank. Genome-wide association studies (GWASs) were conducted to identify single-nucleotide polymorphisms (SNPs) related to AAM-, T2DM-, and T2DM-related phenotypes, such as body fat percentage (BFP), fasting blood glucose (FBG), and hemoglobin A1C (HbA). Further, the conditional false discovery rate (cFDR) method was applied to examine the shared genetic signals. Conditioning on AAM, Quantile-quantile plots showed an earlier departure from the diagonal line among SNPs associated with BFP and FBG, indicating pleiotropic enrichments among AAM and these traits. Further, the cFDR analysis found 39 independent pleiotropic loci that may underlie the AAM-T2DM association. Among them, rs1046896 (cFDR = 6.84 × 10), rs2206734 (cFDR = 6.48 × 10), rs58431774 (cFDR = 2.95 × 10), rs1402837 (cFDR = 1.82 × 10), and rs60808706 (cFDR = 9.49 × 10) were highlighted for their significant genetic enrichment. The protein-protein interaction analysis revealed a significantly enriched network among novel discovered genes that were mostly found to be involved in the insulin and glucagon signaling pathways. Our study highlights potential pleiotropic effects across AAM and T2DM. This may shed light on identifying the genetic causes of T2DM.
初潮年龄（AAM）与2型糖尿病（T2DM）有关。然而，关于它们共同的遗传力知之甚少。我们的数据来自台湾生物银行。进行全基因组关联研究（GWAS）以识别与AAM、T2DM以及T2DM相关表型（如体脂百分比（BFP）、空腹血糖（FBG）和糖化血红蛋白（HbA））相关的单核苷酸多态性（SNP）。此外，应用条件错误发现率（cFDR）方法来检查共享的遗传信号。以AAM为条件，分位数 - 分位数图显示与BFP和FBG相关的SNP中，较早偏离对角线，表明AAM与这些性状之间存在多效性富集。此外，cFDR分析发现39个独立的多效性位点可能是AAM - T2DM关联的基础。其中，rs1046896（cFDR = 6.84×10）、rs2206734（cFDR = 6.48×10）、rs58431774（cFDR = 2.95×10）、rs1402837（cFDR = 1.82×10）和rs60808706（cFDR = 9.49×10）因其显著的基因富集而受到关注。蛋白质 - 蛋白质相互作用分析揭示了新发现基因之间显著富集的网络，这些基因大多参与胰岛素和胰高血糖素信号通路。我们的研究突出了AAM和T2DM之间潜在的多效性作用。这可能有助于揭示T2DM的遗传原因。
