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

被引:6
作者
Wu, Tian [1 ]
Liu, Zipeng [1 ,2 ,3 ]
Mak, Timothy Shin Heng [3 ,4 ]
Sham, Pak Chung [1 ,2 ,3 ]
机构
[1] Univ Hong Kong, Li Ka Shing Fac Med, Dept Psychiat, Hong Kong, Peoples R China
[2] Univ Hong Kong, State Key Lab Brain & Cognit Sci, Hong Kong, Peoples R China
[3] Univ Hong Kong, Li Ka Shing Fac Med, Ctr Panor Sci, Pok Fu Lam, Hong Kong, Peoples R China
[4] Fano Labs, Hong Kong, Peoples R China
基金
中国国家自然科学基金;
关键词
GWAS; polygenic model; power calculation; online tool; statistical method; RISK; HERITABILITY; REGRESSION; INSIGHTS; LINKAGE; SCORES;
D O I
10.3389/fgene.2022.989639
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
引用
收藏
页数:13
相关论文
共 50 条
  • [1] A global reference for human genetic variation
    Altshuler, David M.
    Durbin, Richard M.
    Abecasis, Goncalo R.
    Bentley, David R.
    Chakravarti, Aravinda
    Clark, Andrew G.
    Donnelly, Peter
    Eichler, Evan E.
    Flicek, Paul
    Gabriel, Stacey B.
    Gibbs, Richard A.
    Green, Eric D.
    Hurles, Matthew E.
    Knoppers, Bartha M.
    Korbel, Jan O.
    Lander, Eric S.
    Lee, Charles
    Lehrach, Hans
    Mardis, Elaine R.
    Marth, Gabor T.
    McVean, Gil A.
    Nickerson, Deborah A.
    Wang, Jun
    Wilson, Richard K.
    Boerwinkle, Eric
    Doddapaneni, Harsha
    Han, Yi
    Korchina, Viktoriya
    Kovar, Christie
    Lee, Sandra
    Muzny, Donna
    Reid, Jeffrey G.
    Zhu, Yiming
    Chang, Yuqi
    Feng, Qiang
    Fang, Xiaodong
    Guo, Xiaosen
    Jian, Min
    Jiang, Hui
    Jin, Xin
    Lan, Tianming
    Li, Guoqing
    Li, Jingxiang
    Li, Yingrui
    Liu, Shengmao
    Liu, Xiao
    Lu, Yao
    Ma, Xuedi
    Tang, Meifang
    Wang, Bo
    [J]. NATURE, 2015, 526 (7571) : 68 - +
  • [2] A Systematic Review of Extreme Phenotype Strategies to Search for Rare Variants in Genetic Studies of Complex Disorders
    Amanat, Sana
    Requena, Teresa
    Antonio Lopez-Escamez, Jose
    [J]. GENES, 2020, 11 (09) : 1 - 15
  • [3] Detecting Rare Variant Effects Using Extreme Phenotype Sampling in Sequencing Association Studies
    Barnett, Ian J.
    Lee, Seunggeun
    Lin, Xihong
    [J]. GENETIC EPIDEMIOLOGY, 2013, 37 (02) : 142 - 151
  • [4] A simple yet accurate correction for winner's curse can predict signals discovered in much larger genome scans
    Bigdeli, T. Bernard
    Lee, Donghyung
    Webb, Bradley Todd
    Riley, Brien P.
    Vladimirov, Vladimir I.
    Fanous, Ayman H.
    Kendler, Kenneth S.
    Bacanu, Silviu-Alin
    [J]. BIOINFORMATICS, 2016, 32 (17) : 2598 - 2603
  • [5] LD Score regression distinguishes confounding from polygenicity in genome-wide association studies
    Bulik-Sullivan, Brendan K.
    Loh, Po-Ru
    Finucane, Hilary K.
    Ripke, Stephan
    Yang, Jian
    Patterson, Nick
    Daly, Mark J.
    Price, Alkes L.
    Neale, Benjamin M.
    [J]. NATURE GENETICS, 2015, 47 (03) : 291 - +
  • [6] From GWAS to Function: Using Functional Genomics to Identify the Mechanisms Underlying Complex Diseases
    Cano-Gamez, Eddie
    Trynka, Gosia
    [J]. FRONTIERS IN GENETICS, 2020, 11
  • [7] Projecting the performance of risk prediction based on polygenic analyses of genome-wide association studies
    Chatterjee, Nilanjan
    Wheeler, Bill
    Sampson, Joshua
    Hartge, Patricia
    Chanock, Stephen J.
    Park, Ju-Hyun
    [J]. NATURE GENETICS, 2013, 45 (04) : 400 - 405
  • [8] Accuracy of Predicting the Genetic Risk of Disease Using a Genome-Wide Approach
    Daetwyler, Hans D.
    Villanueva, Beatriz
    Woolliams, John A.
    [J]. PLOS ONE, 2008, 3 (10):
  • [9] Meta-GWAS Accuracy and Power (MetaGAP) Calculator Shows that Hiding Heritability Is Partially Due to Imperfect Genetic Correlations across Studies
    de Vlaming, Ronald
    Okbay, Aysu
    Rietveld, Cornelius A.
    Johannesson, Magnus
    Magnusson, Patrik K. E.
    Uitterlinden, Andre G.
    van Rooij, Frank J. A.
    Hofman, Albert
    Groenen, Patrick J. F.
    Thurik, A. Roy
    Koellinger, Philipp D.
    [J]. PLOS GENETICS, 2017, 13 (01):
  • [10] Power and Predictive Accuracy of Polygenic Risk Scores
    Dudbridge, Frank
    [J]. PLOS GENETICS, 2013, 9 (03):