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Support Interval for Two-Sample Summary Data-Based Mendelian Randomization
The summary-data-based Mendelian randomization (SMR) method is gaining popularity in estimating the causal effect of an exposure on an outcome. In practice, the instrument SNP is often selected from the genome-wide association study (GWAS) on the exposure but no correction is made for such selection...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9859138/ https://www.ncbi.nlm.nih.gov/pubmed/36672952 http://dx.doi.org/10.3390/genes14010211 |
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author | Wang, Kai |
author_facet | Wang, Kai |
author_sort | Wang, Kai |
collection | PubMed |
description | The summary-data-based Mendelian randomization (SMR) method is gaining popularity in estimating the causal effect of an exposure on an outcome. In practice, the instrument SNP is often selected from the genome-wide association study (GWAS) on the exposure but no correction is made for such selection in downstream analysis, leading to a biased estimate of the effect size and invalid inference. We address this issue by using the likelihood derived from the sampling distribution of the estimated SNP effects in the exposure GWAS and the outcome GWAS. This likelihood takes into account how the instrument SNPs are selected. Since the effective sample size is 1, the asymptotic theory does not apply. We use a support for a profile likelihood as an interval estimate of the causal effect. Simulation studies indicate that this support has robust coverage while the confidence interval implied by the SMR method has lower-than-nominal coverage. Furthermore, the variance of the two-stage least squares estimate of the causal effect is shown to be the same as the variance used for SMR for one-sample data when there is no selection. |
format | Online Article Text |
id | pubmed-9859138 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98591382023-01-21 Support Interval for Two-Sample Summary Data-Based Mendelian Randomization Wang, Kai Genes (Basel) Article The summary-data-based Mendelian randomization (SMR) method is gaining popularity in estimating the causal effect of an exposure on an outcome. In practice, the instrument SNP is often selected from the genome-wide association study (GWAS) on the exposure but no correction is made for such selection in downstream analysis, leading to a biased estimate of the effect size and invalid inference. We address this issue by using the likelihood derived from the sampling distribution of the estimated SNP effects in the exposure GWAS and the outcome GWAS. This likelihood takes into account how the instrument SNPs are selected. Since the effective sample size is 1, the asymptotic theory does not apply. We use a support for a profile likelihood as an interval estimate of the causal effect. Simulation studies indicate that this support has robust coverage while the confidence interval implied by the SMR method has lower-than-nominal coverage. Furthermore, the variance of the two-stage least squares estimate of the causal effect is shown to be the same as the variance used for SMR for one-sample data when there is no selection. MDPI 2023-01-13 /pmc/articles/PMC9859138/ /pubmed/36672952 http://dx.doi.org/10.3390/genes14010211 Text en © 2023 by the author. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wang, Kai Support Interval for Two-Sample Summary Data-Based Mendelian Randomization |
title | Support Interval for Two-Sample Summary Data-Based Mendelian Randomization |
title_full | Support Interval for Two-Sample Summary Data-Based Mendelian Randomization |
title_fullStr | Support Interval for Two-Sample Summary Data-Based Mendelian Randomization |
title_full_unstemmed | Support Interval for Two-Sample Summary Data-Based Mendelian Randomization |
title_short | Support Interval for Two-Sample Summary Data-Based Mendelian Randomization |
title_sort | support interval for two-sample summary data-based mendelian randomization |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9859138/ https://www.ncbi.nlm.nih.gov/pubmed/36672952 http://dx.doi.org/10.3390/genes14010211 |
work_keys_str_mv | AT wangkai supportintervalfortwosamplesummarydatabasedmendelianrandomization |