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On Mendelian randomization analysis of case‐control study
Author(s) -
Zhang Han,
Qin Jing,
Berndt Sonja I.,
Albanes Demetrius,
Deng Lu,
Gail Mitchell H.,
Yu Kai
Publication year - 2020
Publication title -
biometrics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.298
H-Index - 130
eISSN - 1541-0420
pISSN - 0006-341X
DOI - 10.1111/biom.13166
Subject(s) - mendelian randomization , randomization , computer science , control (management) , statistics , computational biology , mathematics , biology , bioinformatics , artificial intelligence , genetics , clinical trial , gene , genetic variants , genotype
Mendelian randomization (MR) analysis uses genotypes as instruments to estimate the causal effect of an exposure in the presence of unobserved confounders. The existing MR methods focus on the data generated from prospective cohort studies. We develop a procedure for studying binary outcomes under a case‐control design. The proposed procedure is built upon two working models commonly used for MR analyses and adopts a quasi‐empirical likelihood framework to address the ascertainment bias from case‐control sampling. We derive various approaches for estimating the causal effect and hypothesis testing under the empirical likelihood framework. We conduct extensive simulation studies to evaluate the proposed methods. We find that the proposed empirical likelihood estimate is less biased than the existing estimates. Among all the approaches considered, the Lagrange multiplier (LM) test has the highest power, and the confidence intervals derived from the LM test have the most accurate coverage. We illustrate the use of our method in MR analysis of prostate cancer case‐control data with vitamin D level as exposure and three single nucleotide polymorphisms as instruments.