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Polygenic power calculator: Statistical power and polygenic prediction accuracy of genome-wide association studies of complex traits

Power calculation is a necessary step when planning genome-wide association studies (GWAS) to ensure meaningful findings. Statistical power of GWAS depends on the genetic architecture of phenotype, sample size, and study design. While several computer programs have been developed to perform power ca...

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Detalles Bibliográficos
Autores principales: Wu, Tian, Liu, Zipeng, Mak, Timothy Shin Heng, Sham, Pak Chung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9589038/
https://www.ncbi.nlm.nih.gov/pubmed/36299579
http://dx.doi.org/10.3389/fgene.2022.989639
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author Wu, Tian
Liu, Zipeng
Mak, Timothy Shin Heng
Sham, Pak Chung
author_facet Wu, Tian
Liu, Zipeng
Mak, Timothy Shin Heng
Sham, Pak Chung
author_sort Wu, Tian
collection PubMed
description Power calculation is a necessary step when planning genome-wide association studies (GWAS) to ensure meaningful findings. Statistical power of GWAS depends on the genetic architecture of phenotype, sample size, and study design. While several computer programs have been developed to perform power calculation for single SNP association testing, it might be more appropriate for GWAS power calculation to address the probability of detecting any number of associated SNPs. In this paper, we derive the statistical power distribution across causal SNPs under the assumption of a point-normal effect size distribution. We demonstrate how key outcome indices of GWAS are related to the genetic architecture (heritability and polygenicity) of the phenotype through the power distribution. We also provide a fast, flexible and interactive power calculation tool which generates predictions for key GWAS outcomes including the number of independent significant SNPs, the phenotypic variance explained by these SNPs, and the predictive accuracy of resulting polygenic scores. These results could also be used to explore the future behaviour of GWAS as sample sizes increase further. Moreover, we present results from simulation studies to validate our derivation and evaluate the agreement between our predictions and reported GWAS results.
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spelling pubmed-95890382022-10-25 Polygenic power calculator: Statistical power and polygenic prediction accuracy of genome-wide association studies of complex traits Wu, Tian Liu, Zipeng Mak, Timothy Shin Heng Sham, Pak Chung Front Genet Genetics Power calculation is a necessary step when planning genome-wide association studies (GWAS) to ensure meaningful findings. Statistical power of GWAS depends on the genetic architecture of phenotype, sample size, and study design. While several computer programs have been developed to perform power calculation for single SNP association testing, it might be more appropriate for GWAS power calculation to address the probability of detecting any number of associated SNPs. In this paper, we derive the statistical power distribution across causal SNPs under the assumption of a point-normal effect size distribution. We demonstrate how key outcome indices of GWAS are related to the genetic architecture (heritability and polygenicity) of the phenotype through the power distribution. We also provide a fast, flexible and interactive power calculation tool which generates predictions for key GWAS outcomes including the number of independent significant SNPs, the phenotypic variance explained by these SNPs, and the predictive accuracy of resulting polygenic scores. These results could also be used to explore the future behaviour of GWAS as sample sizes increase further. Moreover, we present results from simulation studies to validate our derivation and evaluate the agreement between our predictions and reported GWAS results. Frontiers Media S.A. 2022-10-10 /pmc/articles/PMC9589038/ /pubmed/36299579 http://dx.doi.org/10.3389/fgene.2022.989639 Text en Copyright © 2022 Wu, Liu, Mak and Sham. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Wu, Tian
Liu, Zipeng
Mak, Timothy Shin Heng
Sham, Pak Chung
Polygenic power calculator: Statistical power and polygenic prediction accuracy of genome-wide association studies of complex traits
title Polygenic power calculator: Statistical power and polygenic prediction accuracy of genome-wide association studies of complex traits
title_full Polygenic power calculator: Statistical power and polygenic prediction accuracy of genome-wide association studies of complex traits
title_fullStr Polygenic power calculator: Statistical power and polygenic prediction accuracy of genome-wide association studies of complex traits
title_full_unstemmed Polygenic power calculator: Statistical power and polygenic prediction accuracy of genome-wide association studies of complex traits
title_short Polygenic power calculator: Statistical power and polygenic prediction accuracy of genome-wide association studies of complex traits
title_sort polygenic power calculator: statistical power and polygenic prediction accuracy of genome-wide association studies of complex traits
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9589038/
https://www.ncbi.nlm.nih.gov/pubmed/36299579
http://dx.doi.org/10.3389/fgene.2022.989639
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