Semiparametric methods for estimation of a nonlinear exposure-outcome relationship using instrumental variables with application to Mendelian randomization.
Semiparametric methods for estimation of a nonlinear exposure-outcome relationship using instrumental variables with application to Mendelian randomization.
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DOI：
10.1002/gepi.22041
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发表时间：
2017-05
影响因子：
2.1
通讯作者：
Burgess S
中科院分区：
文献类型：
--
作者：
Staley JR;Burgess S
孟德尔随机化，使用遗传变异作为工具变量（IV），可以测试和估计暴露对结果的因果影响。大多数IV方法假设暴露量与结果预期值之间的函数（暴露量-结果关系）是线性的。然而，在实践中，这一假设可能并不成立。事实上，人们感兴趣的主要问题往往是评估这种关系的形态。我们提出了两种新的IV方法来研究暴露-结果关系的形状：分数多项式方法和分段线性方法。我们使用暴露分布将人口划分为阶层，并估计每个阶层人口中的因果效应，称为局部平均因果效应（LACE）。分数多项式方法对这些LACE估计值执行元回归。分段线性方法估计连续分段线性函数，其梯度是每个层中的LACE估计。在模拟研究中证明了这两种方法可以很好地估计真实的暴露-结局关系，特别是当关系是分数多项式（对于分数多项式方法）或分段线性（对于分段线性方法）时。采用上述方法研究了体重指数与收缩压、舒张压的关系形态。
Mendelian randomization, the use of genetic variants as instrumental variables (IV), can test for and estimate the causal effect of an exposure on an outcome. Most IV methods assume that the function relating the exposure to the expected value of the outcome (the exposure‐outcome relationship) is linear. However, in practice, this assumption may not hold. Indeed, often the primary question of interest is to assess the shape of this relationship. We present two novel IV methods for investigating the shape of the exposure‐outcome relationship: a fractional polynomial method and a piecewise linear method. We divide the population into strata using the exposure distribution, and estimate a causal effect, referred to as a localized average causal effect (LACE), in each stratum of population. The fractional polynomial method performs metaregression on these LACE estimates. The piecewise linear method estimates a continuous piecewise linear function, the gradient of which is the LACE estimate in each stratum. Both methods were demonstrated in a simulation study to estimate the true exposure‐outcome relationship well, particularly when the relationship was a fractional polynomial (for the fractional polynomial method) or was piecewise linear (for the piecewise linear method). The methods were used to investigate the shape of relationship of body mass index with systolic blood pressure and diastolic blood pressure.