PASTRY: achieving balanced power for detecting risk and protective minor alleles in meta-analysis of association studies with overlapping subjects

Background Meta-analysis is a statistical method that combines the results of multiple studies to increase statistical power. When multiple studies participating in a meta-analysis utilize the same public dataset as controls, the summary statistics from these studies become correlated. To solve this...

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Bibliographic Details
Published in:BMC bioinformatics Vol. 25; no. 1; pp. 24 - 19
Main Authors: Kim, Emma E., Jang, Chloe Soohyun, Kim, Hakin, Han, Buhm
Format: Journal Article
Language:English
Published: London BioMed Central 12.01.2024
BioMed Central Ltd
Springer Nature B.V
BMC
Subjects:
Algorithms
Alleles
Allelomorphism
Asymmetry
Binomial distribution
Bioinformatics
Biomedical and Life Sciences
Computational Biology/Bioinformatics
Computer Appl. in Life Sciences
Correlation
Correlation (Statistics)
Datasets
Disease
Genetic research
Genome-wide association studies
GWAS
Hypotheses
Life Sciences
Meta-analysis
Methods
Microarrays
Overlapping subjects
Pastries
Regression analysis
Sample size
Simulation
Statistical analysis
Statistical methods
Statistics
South Korea
Correlation
GWAS
Methods
Meta-analysis
Overlapping subjects
ISSN:1471-2105, 1471-2105
Online Access:Get full text
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Summary:Background Meta-analysis is a statistical method that combines the results of multiple studies to increase statistical power. When multiple studies participating in a meta-analysis utilize the same public dataset as controls, the summary statistics from these studies become correlated. To solve this challenge, Lin and Sullivan proposed a method to provide an optimal test statistic adjusted for the correlation. This method quickly became the standard practice. However, we identified an unexpected power asymmetry phenomenon in this standard framework. This can lead to unbalanced power for detecting protective minor alleles and risk minor alleles. Results We found that the power asymmetry of the current framework is mainly due to the errors in approximating the correlation term. We then developed a meta-analysis method based on an accurate correlation estimator, called PASTRY (A method to avoid Power ASymmeTRY). PASTRY outperformed the standard method on both simulated and real datasets in terms of the power symmetry. Conclusions Our findings suggest that PASTRY can help to alleviate the power asymmetry problem. PASTRY is available at https://github.com/hanlab-SNU/PASTRY .
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ISSN:1471-2105
1471-2105
DOI:10.1186/s12859-023-05627-z