通讯作者: 杨 韵▲, 13751772695@163.com

DOI：10.12201/bmr.202606.00067

Trans-pQTL analysis for the causal association between layilin and breast cancer

• 摘要：目的：采用反式蛋白数量性状位点(trans-pQTL)作为工具变量,从远端遗传调控角度评估透明质酸受体(LAYN)蛋白水平与乳腺癌发病及生存的因果关系。方法：S采用两样本孟德尔随机化(MR)设计,暴露数据来自Sun等(2018)血浆蛋白质组全基因组关联研究(GWAS,样本量3301例),结局数据来自乳腺癌协会联盟(BCAC)。采用双阈值筛选方法：(1)严格阈值(P<5×10??)纳入2个trans-pQTL；(2)宽松阈值(P<5×10??)纳入19个trans-pQTL。以逆方差加权法(IVW)为主分析,联合孟德尔随机化-埃格回归法(MR-Egger)、加权中位数法、加权模式法及孟德尔随机化-偏倚残差和离群值检验法(MR-PRESSO)进行敏感性分析。采用邦费罗尼校正(Bonferroni,α=0.0083)。结果：S宽松阈值组分析显示,LAYN与总体乳腺癌、雌激素受体阳性(ER+)、雌激素受体阴性(ER-)乳腺癌发病风险及生存均无因果关联(P>0.0083)。严格阈值验证结果一致。MR-PRESSO仅在ER+乳腺癌生存中检出1个离群单核苷酸多态性(SNP),剔除该SNP后IVW分析结果无明显变化。结论：S无论采用宽松还是严格阈值,本研究均未检测到LAYN蛋白水平与乳腺癌发病及生存存在统计学显著的因果关联。本研究统计效能限制,仅能排除中等及以上效应(OR/HR≥1.07),无法对更小的效应做出推断。

  关键词： 透明质酸受体，乳腺癌，孟德尔随机化，生存分析; ; ; 

   

  Abstract: Objective:STo assess the causal association between genetically predicted layilin (LAYN) protein levels and breast cancer risk and survival using trans-protein quantitative trait loci (trans-pQTLs) as instrumental variables from the perspective of distal genetic regulation.Methods:SA two-sample Mendelian randomization (MR) design was adopted. Exposure data were obtained from the plasma proteome genome-wide association study (GWAS) by Sun et al. (2018, n=3301), and outcome data were obtained from the Breast Cancer Association Consortium (BCAC). A dual-threshold selection strategy was applied: (1) a strict threshold (P<5×10??) identified 2 trans-pQTLs; (2) a lenient threshold (P<5×10??) identified 19 trans-pQTLs. The inverse variance weighted (IVW) method was used as the primary analysis, supplemented by MR-Egger, weighted median, weighted mode, and MR-PRESSO for sensitivity analyses. Bonferroni correction (α=0.0083) was applied.Results:SUsing the lenient threshold, no causal association was observed between LAYN and the risk or survival of overall breast cancer, estrogen receptor-positive (ER+), or estrogen receptor-negative (ER-) breast cancer (all P>0.0083). The strict threshold validation yielded consistent null results. MR-PRESSO identified one outlier single nucleotide polymorphism (SNP) only in ER+ breast cancer survival; removing this SNP did not materially change the IVW results.Conclusion:SRegardless of using the lenient or strict threshold, this study detected no statistically significant causal association between LAYN protein levels and breast cancer risk or survival. Due to limited statistical power, this study can only exclude moderate-to-large effects (OR/HR ≥1.07), and cannot make inferences about smaller effects.

  Key words: Layilin, Breast; cancer, Mendelian; randomization, Survival; analysis

  提交时间：2026-06-22

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• 序号	提交日期	编号	操作
  1	2026-06-02	10.12201/bmr.202606.00067V1	下载

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