ArticleEuropean journal of human genetics : EJHG2013
Empirical power of very rare variants for common traits and disease: results from sanger sequencing 1998 individuals.
Article in European journal of human genetics : EJHG, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Genetic architecture: the shape of the genetic contribution to human traits and disease.Nature reviews. Genetics · 2018Review
- A pathway-centric approach to rare variant association analysis.European journal of human genetics : EJHG · 2016Article
- Meta-Analysis of Rare Variant Association Tests in Multiethnic Populations.Genetic epidemiology · 2016Article
- Article
- Targeted massively parallel sequencing of autism spectrum disorder-associated genes in a case control cohort reveals rare loss-of-function risk variants.Molecular autism · 2015Article
- Performance of genotype imputation for low frequency and rare variants from the 1000 genomes.PloS one · 2015Article
- Variant association tools for quality control and analysis of large-scale sequence and genotyping array data.American journal of human genetics · 2014Article
- Statistical power and significance testing in large-scale genetic studies.Nature reviews. Genetics · 2014Review
- Regularized rare variant enrichment analysis for case-control exome sequencing data.Genetic epidemiology · 2014Article
- Exploring the potential benefits of stratified false discovery rates for region-based testing of association with rare genetic variation.Frontiers in genetics · 2014Article
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4 authors.
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Abstract
The optimal study design for identifying rare variants associated with common disease is not yet clear and researchers have to decide whether to prioritize lower sequencing coverage on larger sample sizes, or higher coverage on smaller sample sizes. High-coverage sequencing affords several advantages, such as genotype accuracy and improved identification of very rare variants, but this comes at increased cost. However, the magnitude of the contribution of very rare variants to the statistical power of gene-based association tests is unknown. By using Sanger sequence data on seven genes from 1998 subjects with simulated phenotypes, we provide evidence that excluding very rare variants, in general, reduces the statistical power of rare variant association tests only modestly. However, if the probability of being causal and the effect size of the causal variants are inversely related to the minor allele frequency, then very rare variants do contribute to some power, however the absolute power remains low. As very rare variants constitute the majority of variants identified in sequencing studies, these findings suggest that careful attention need to be placed on the plausible relationship that exist between very rare variants and common disease.
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