ArticlePLoS genetics2012
The empirical power of rare variant association methods: results from sanger sequencing in 1,998 individuals.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 2 of them syntheses that pooled it.
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Who cites it
75 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Methods for the Analysis and Interpretation for Rare Variants Associated with Complex Traits.Current protocols in human genetics · 2019Pooled it
- Meta-analysis of gene-level tests for rare variant association.Nature genetics · 2014Pooled it
- Rare genomic structural variants in complex disease: lessons from the replication of associations with obesity.PloS one · 2013Trial
- Rare-variant association studies: When are aggregation tests more powerful than single-variant tests?American journal of human genetics · 2025Article
- Article
- Review
- Excalibur: A new ensemble method based on an optimal combination of aggregation tests for rare-variant association testing for sequencing data.PLoS computational biology · 2023Article
- Rare variant association testing in the non-coding genome.Human genetics · 2020Review
- Multi-Set Testing Strategies Show Good Behavior When Applied to Very Large Sets of Rare Variants.Frontiers in genetics · 2020Article
- Meta-Qtest: meta-analysis of quadratic test for rare variants.BMC medical genomics · 2019Article
- Genetic architecture: the shape of the genetic contribution to human traits and disease.Nature reviews. Genetics · 2018Review
- Exome-wide rare variant analyses of two bone mineral density phenotypes: the challenges of analyzing rare genetic variation.Scientific reports · 2018Article
- Genetic variants including markers from the exome chip and metabolite traits of type 2 diabetes.Scientific reports · 2017Article
- On the association analysis of genome-sequencing data: A spatial clustering approach for partitioning the entire genome into nonoverlapping windows.Genetic epidemiology · 2017Article
- Whole-exome sequencing of 228 patients with sporadic Parkinson's disease.Scientific reports · 2017Article
- Comparison of single-marker and multi-marker tests in rare variant association studies of quantitative traits.PloS one · 2017Article
- AP-SKAT: highly-efficient genome-wide rare variant association test.BMC genomics · 2016Article
- Gene-set association tests for next-generation sequencing data.Bioinformatics (Oxford, England) · 2016Article
- Phenotypic extremes in rare variant study designs.European journal of human genetics : EJHG · 2016Article
- Multi-Population Selective Genotyping to Identify Soybean [Glycine max (L.) Merr.] Seed Protein and Oil QTLs.G3 (Bethesda, Md.) · 2016Article
15 more citing papers are in PubMed but not listed here.
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5 authors.
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Abstract
The role of rare genetic variation in the etiology of complex disease remains unclear. However, the development of next-generation sequencing technologies offers the experimental opportunity to address this question. Several novel statistical methodologies have been recently proposed to assess the contribution of rare variation to complex disease etiology. Nevertheless, no empirical estimates comparing their relative power are available. We therefore assessed the parameters that influence their statistical power in 1,998 individuals Sanger-sequenced at seven genes by modeling different distributions of effect, proportions of causal variants, and direction of the associations (deleterious, protective, or both) in simulated continuous trait and case/control phenotypes. Our results demonstrate that the power of recently proposed statistical methods depend strongly on the underlying hypotheses concerning the relationship of phenotypes with each of these three factors. No method demonstrates consistently acceptable power despite this large sample size, and the performance of each method depends upon the underlying assumption of the relationship between rare variants and complex traits. Sensitivity analyses are therefore recommended to compare the stability of the results arising from different methods, and promising results should be replicated using the same method in an independent sample. These findings provide guidance in the analysis and interpretation of the role of rare base-pair variation in the etiology of complex traits and diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.