ArticlePLoS genetics2014
Identification of rare causal variants in sequence-based studies: methods and applications to VPS13B, a gene involved in Cohen syndrome and autism.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Trans-ethnic meta-analysis of rare variants in sequencing association studies.Biostatistics (Oxford, England) · 2021Pooled it
- Selenium-Related Genes Modulate Susceptibility to Parkinson's Disease Via Combination and SNCA-Interactive Effects Rather than Independent Effects: A Case-Control Study.Biological trace element research · 2026Article
- Impact of genetic test interpretation on aFrontiers in neuroscience · 2024Article
- Machine learning in rare disease.Nature methods · 2023Review
- Disease relevance of rare VPS13B missense variants for neurodevelopmental Cohen syndrome.Scientific reports · 2022Article
- Multivariate, region-based genetic analyses of facets of reproductive aging in White and Black women.Molecular genetics & genomic medicine · 2022Article
- Whole exome sequencing in Alopecia Areata identifies rare variants in KRT82.Nature communications · 2022Article
- Polymorphisms of Cytochromes P450 and Glutathione S-Transferases Synergistically Modulate Risk for Parkinson's Disease.Frontiers in aging neuroscience · 2022Article
- A Bayesian hierarchically structured prior for rare-variant association testing.Genetic epidemiology · 2021Article
- XK is a partner for VPS13A: a molecular link between Chorea-Acanthocytosis and McLeod Syndrome.Molecular biology of the cell · 2020Article
- Cohen Syndrome-Associated Cataract Is Explained by VPS13B Functions in Lens Homeostasis and Is Modified by Additional Genetic Factors.Investigative ophthalmology & visual science · 2020Article
- Meta-MultiSKAT: Multiple phenotype meta-analysis for region-based association test.Genetic epidemiology · 2019Article
- A review of kernel methods for genetic association studies.Genetic epidemiology · 2019Review
- Identifying individual risk rare variants using protein structure guided local tests (POINT).PLoS computational biology · 2019Article
- Multi-SKAT: General framework to test for rare-variant association with multiple phenotypes.Genetic epidemiology · 2019Article
- Multiple rare and common variants in APOB gene locus associated with oxidatively modified low-density lipoprotein levels.PloS one · 2019Article
- Comprehensive Analysis of Rare Variants of 101 Autism-Linked Genes in a Hungarian Cohort of Autism Spectrum Disorder Patients.Frontiers in genetics · 2019Article
- Prenatal Neuropathologies in Autism Spectrum Disorder and Intellectual Disability: The Gestation of a Comprehensive Zebrafish Model.Journal of developmental biology · 2018Review
- FUN-LDA: A Latent Dirichlet Allocation Model for Predicting Tissue-Specific Functional Effects of Noncoding Variation: Methods and Applications.American journal of human genetics · 2018Article
- FineMAV: prioritizing candidate genetic variants driving local adaptations in human populations.Genome biology · 2018Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
Pinpointing the small number of causal variants among the abundant naturally occurring genetic variation is a difficult challenge, but a crucial one for understanding precise molecular mechanisms of disease and follow-up functional studies. We propose and investigate two complementary statistical approaches for identification of rare causal variants in sequencing studies: a backward elimination procedure based on groupwise association tests, and a hierarchical approach that can integrate sequencing data with diverse functional and evolutionary conservation annotations for individual variants. Using simulations, we show that incorporation of multiple bioinformatic predictors of deleteriousness, such as PolyPhen-2, SIFT and GERP++ scores, can improve the power to discover truly causal variants. As proof of principle, we apply the proposed methods to VPS13B, a gene mutated in the rare neurodevelopmental disorder called Cohen syndrome, and recently reported with recessive variants in autism. We identify a small set of promising candidates for causal variants, including two loss-of-function variants and a rare, homozygous probably-damaging variant that could contribute to autism risk.
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Registered trials
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.