Cited by 573Genetic Associations and EpidemiologyStatistical Methods in Clinical TrialsGenomics and Rare Diseases

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Statistical power and significance testing in large-scale genetic studies

Sham, Pak C., Purcell, Shaun M.·2014·Nature Reviews Genetics

Abstract

Significance testing was developed as an objective method for summarizing statistical evidence for a hypothesis. It has been widely adopted in genetic studies, including genome-wide association studies and, more recently, exome sequencing studies. However, significance testing in both genome-wide and exome-wide studies must adopt stringent significance thresholds to allow multiple testing, and it is useful only when studies have adequate statistical power, which depends on the characteristics of the phenotype and the putative genetic variant, as well as the study design. Here, we review the principles and applications of significance testing and power calculation, including recently proposed gene-based tests for rare variants.

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Crossref · 10.1038/nrg3706

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Metadata

Authors
Sham, P. C., & Purcell, S. M.
Affiliations
  • University of Hong Kong (HK)
  • Massachusetts General Hospital (US)
Corresponding author
Sham, Pak C.
Venue
Nature Reviews Genetics
Published
2014-04-17
Volume
15
Issue
5
Pages
335-346
ISSN
  • 1471-0056 (ISSN-L)
  • 1471-0064
OpenAlex
W2116514399
Cited by
573
References
102
Citations by year
2026: 23 · 2025: 26 · 2024: 22 · 2023: 50 · 2022: 28 · 2021: 40 · 2020: 54 · 2019: 58 · 2018: 73 · 2017: 77 · 2016: 65 · 2015: 45 · 2014: 11
FWCI
8.75
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Reviews Genetics (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute of Mental Health (R01MH099126)
  • National Human Genome Research Institute (R01HG005827)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
Keywords
statistical power, significance testing, multiple testing correction, rare variants, genome-wide association study, exome sequencing, significance threshold, research design
MeSH terms
Data Interpretation, Statistical, Gene Frequency, Genetic Testing, Genotype, Humans, Case-Control Studies, Sequence Analysis, DNA, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genome-Wide Association Study

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