2018
DOI: 10.1038/s41588-018-0099-7
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Abstract: Horizontal pleiotropy occurs when the variant has an effect on disease outside of its effect on the exposure in Mendelian randomization (MR). Violation of the ‘no horizontal pleiotropy’ assumption can cause severe bias in MR. We developed the Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test to identify horizontal pleiotropic outliers in multi-instrument summary-level MR testing. We showed using simulations that MR-PRESSO is best suited when horizontal pleiotropy occurs in <50% of in… Show more

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Cited by 3,714 publications
(2,881 citation statements)
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References 42 publications
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“…25 We then used the MR-PRESSO global test to identify the potential horizontal pleiotropic effects of the SNPs (p < 1 × 10 −6 ). 26 Specifically, based on the null hypothesis of no horizontal pleiotropy, the overall horizontal pleiotropy among SNPs can be evaluated by comparing the observed residual sum of squares to the expected residual sum of squares. 26 We further performed a series of sensitivity analyses to improve the reliability of the association between the genetic instruments and the exposure.…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…25 We then used the MR-PRESSO global test to identify the potential horizontal pleiotropic effects of the SNPs (p < 1 × 10 −6 ). 26 Specifically, based on the null hypothesis of no horizontal pleiotropy, the overall horizontal pleiotropy among SNPs can be evaluated by comparing the observed residual sum of squares to the expected residual sum of squares. 26 We further performed a series of sensitivity analyses to improve the reliability of the association between the genetic instruments and the exposure.…”
Section: Resultsmentioning
confidence: 99%
“…26 Specifically, based on the null hypothesis of no horizontal pleiotropy, the overall horizontal pleiotropy among SNPs can be evaluated by comparing the observed residual sum of squares to the expected residual sum of squares. 26 We further performed a series of sensitivity analyses to improve the reliability of the association between the genetic instruments and the exposure. We applied leave-one-out analyses to identify SNPs that could potentially bias the causal association.…”
Section: Resultsmentioning
confidence: 99%
“…Analysis was performed using R version 3.4.3 software (R Foundation for Statistical Computing) together with the R packages gtx and MR‐PRESSO . The list of genetic variants used appear in Supplementary Table 1.…”
Section: Methodsmentioning
confidence: 99%
“…Analysis was performed using R version 3.4.3 software (R Foundation for Statistical Computing) together with the R packages gtx and MR-PRESSO. 30 The list of genetic variants used appear in Supplementary Table 1. This study used publicly available deidentified data from participating studies that had already obtained relevant authorization from local ethics and/or institutional review boards.…”
Section: Mediation Analysismentioning
confidence: 99%
“…24 This test identifies possible bias from horizontal pleiotropy. 24 This test identifies possible bias from horizontal pleiotropy.…”
Section: Mr-presso Analysismentioning
confidence: 99%