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

DOI: 10.12201/bmr.202606.00067

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  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

  Submit time: 22 June 2026

  Copyright: The copyright holder for this preprint is the author/funder, who has granted biomedRxiv a license to display the preprint in perpetuity.
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