ArticlePloS one2013
Fine-scale patterns of population stratification confound rare variant association tests.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Evaluating confounding in rare variant genome wide association studies.Nature communications · 2026Article
- How human genetic context can inform pathogenicity classification: FGFR1 variation in idiopathic hypogonadotropic hypogonadism.Human genetics · 2023Article
- Strategies for the Genomic Analysis of Admixed Populations.Annual review of biomedical data science · 2023Review
- Fast and accurate Bayesian polygenic risk modeling with variational inference.American journal of human genetics · 2023Article
- Opportunities and challenges for the use of common controls in sequencing studies.Nature reviews. Genetics · 2022Review
- Taking population stratification into account by local permutations in rare-variant association studies on small samples.Genetic epidemiology · 2021Article
- Controlling for human population stratification in rare variant association studies.Scientific reports · 2021Article
- Rare deleterious germline variants and risk of lung cancer.NPJ precision oncology · 2021Article
- Article
- Gene association detection via local linear regression method.Journal of human genetics · 2020Article
- Determining population stratification and subgroup effects in association studies of rare genetic variants for nicotine dependence.Psychiatric genetics · 2019Article
- Burden Testing of Rare Variants Identified through Exome Sequencing via Publicly Available Control Data.American journal of human genetics · 2018Article
- On the substructure controls in rare variant analysis: Principal components or variance components?Genetic epidemiology · 2018Article
- The impact of a fine-scale population stratification on rare variant association test results.PloS one · 2018Article
- A Wide and Specific Spectrum of Genetic Variants and Genotype-Phenotype Correlations Revealed by Next-Generation Sequencing in Patients with Left Ventricular Noncompaction.Journal of the American Heart Association · 2017Article
- The impact of rare and low-frequency genetic variants in common disease.Genome biology · 2017Review
- DoEstRare: A statistical test to identify local enrichments in rare genomic variants associated with disease.PloS one · 2017Article
- Relationship between polycystic ovary syndrome and ancestry in European Americans.Fertility and sterility · 2016Article
- Identification of low frequency and rare variants for hypertension using sparse-data methods.BMC proceedings · 2016Article
- Meta-Analysis of Rare Variant Association Tests in Multiethnic Populations.Genetic epidemiology · 2016Article
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10 authors.
Funding
Abstract
Advances in next-generation sequencing technology have enabled systematic exploration of the contribution of rare variation to Mendelian and complex diseases. Although it is well known that population stratification can generate spurious associations with common alleles, its impact on rare variant association methods remains poorly understood. Here, we performed exhaustive coalescent simulations with demographic parameters calibrated from exome sequence data to evaluate the performance of nine rare variant association methods in the presence of fine-scale population structure. We find that all methods have an inflated spurious association rate for parameter values that are consistent with levels of differentiation typical of European populations. For example, at a nominal significance level of 5%, some test statistics have a spurious association rate as high as 40%. Finally, we empirically assess the impact of population stratification in a large data set of 4,298 European American exomes. Our results have important implications for the design, analysis, and interpretation of rare variant genome-wide association studies.
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