A Linear Mixed Model with Measurement Error Correction (LMM-MEC): A Method for Summary-data-based Multivariable Mendelian Randomization.

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Tác giả: Ming Ding, Fei Zou

Ngôn ngữ: eng

Ký hiệu phân loại: 636.0885 Animal husbandry

Thông tin xuất bản: United States : medRxiv : the preprint server for health sciences , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 151658

 Summary-data-based multivariable Mendelian randomization (MVMR) methods, such as MVMR-Egger, MVMR-IVW, MVMR median-based, and MVMR-PRESSO, assess the causal effects of multiple risk factors on disease. However, accounting for variances in summary statistics related to risk factors remains a challenge. We propose a linear mixed model with measurement error correction (LMM-MEC) that accounts for the variance of summary statistics for both disease outcomes and risk factors. In step I, a linear mixed model is applied to account for the variance in disease summary statistics. Specifically, if heterogeneity is present in disease summary statistics, we treat it as a random effect and adopt an iteratively re-weighted least squares algorithm to estimate causal effects. In step II, we treat the variance in the summary statistics of risk factors as multiple measurement errors and apply a regression calibration method for simultaneous multiple measurement error correction. In a simulation study, when using independent genetic variants as instrumental variables (IV), our method showed comparable performance to existing MVMR methods under conditions of no pleiotropy or balanced pleiotropy with the outcome, and it exhibited higher coverage rates and power under directional pleiotropy. Similar findings were observed when using genetic variants with low to moderate linkage disequilibrium (LD) (0 <
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