{"title":"Interval estimate of causal effect in summary data based Mendelian randomization in the presence of winner's curse","authors":"Kai Wang","doi":"10.1002/gepi.22545","DOIUrl":null,"url":null,"abstract":"<p>This research focuses on the interval estimation of the causal effect of an exposure on an outcome using the summary data-based Mendelian randomization (SMR) method while accounting for the winner's curse caused by the selection of single nucleotide polymorphism instruments. This issue is understudied and is important as the point estimate is biased. Since Fieller's theorem and its variations are not suitable for constructing a confidence interval, we use the box method. This box method is known to be conservative and thus provides a lower bound on the coverage level. To assess the performance of the box method, we use simulation studies and compare it with the support interval we proposed earlier and the Wald interval derived from the SMR method. All three methods are applied to a study of causal genes for Alzheimer's disease. Overall, the box method presents an alternative for constructing interval estimates for a causal effect while addressing the winner's curse issue.</p>","PeriodicalId":12710,"journal":{"name":"Genetic Epidemiology","volume":"48 2","pages":"74-84"},"PeriodicalIF":1.7000,"publicationDate":"2024-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gepi.22545","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genetic Epidemiology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/gepi.22545","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
This research focuses on the interval estimation of the causal effect of an exposure on an outcome using the summary data-based Mendelian randomization (SMR) method while accounting for the winner's curse caused by the selection of single nucleotide polymorphism instruments. This issue is understudied and is important as the point estimate is biased. Since Fieller's theorem and its variations are not suitable for constructing a confidence interval, we use the box method. This box method is known to be conservative and thus provides a lower bound on the coverage level. To assess the performance of the box method, we use simulation studies and compare it with the support interval we proposed earlier and the Wald interval derived from the SMR method. All three methods are applied to a study of causal genes for Alzheimer's disease. Overall, the box method presents an alternative for constructing interval estimates for a causal effect while addressing the winner's curse issue.
期刊介绍：
Genetic Epidemiology is a peer-reviewed journal for discussion of research on the genetic causes of the distribution of human traits in families and populations. Emphasis is placed on the relative contribution of genetic and environmental factors to human disease as revealed by genetic, epidemiological, and biologic investigations.
Genetic Epidemiology primarily publishes papers in statistical genetics, a research field that is primarily concerned with development of statistical, bioinformatical, and computational models for analyzing genetic data. Incorporation of underlying biology and population genetics into conceptual models is favored. The Journal seeks original articles comprising either applied research or innovative statistical, mathematical, computational, or genomic methodologies that advance studies in genetic epidemiology. Other types of reports are encouraged, such as letters to the editor, topic reviews, and perspectives from other fields of research that will likely enrich the field of genetic epidemiology.
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