ArticleHuman mutation2015
Mitigating false-positive associations in rare disease gene discovery.
Article in Human mutation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- A Zebra in Horse's Clothing: Rethinking the Diagnosis of Rare Diseases.Molecular genetics & genomic medicine · 2025Review
- Seven years since the launch of the Matchmaker Exchange: The evolution of genomic matchmaking.Human mutation · 2022Article
- Candidate genes and sequence variants for susceptibility to mycobacterial infection identified by whole-exome sequencing.Frontiers in genetics · 2022Article
- Variants in STXBP3 are Associated with Very Early Onset Inflammatory Bowel Disease, Bilateral Sensorineural Hearing Loss and Immune Dysregulation.Journal of Crohn's & colitis · 2021Article
- A Survey of Compound Heterozygous Variants in Pediatric Cancers and Structural Birth Defects.Frontiers in genetics · 2021Article
- Exome association analysis sheds light onto leaf rust (Puccinia triticina) resistance genes currently used in wheat breeding (Triticum aestivum L.).Plant biotechnology journal · 2020Article
- Article
- Enabling Global Clinical Collaborations on Identifiable Patient Data: The Minerva Initiative.Frontiers in genetics · 2019Article
- MECP2 variation in Rett syndrome-An overview of current coverage of genetic and phenotype data within existing databases.Human mutation · 2018Article
- Calculating the statistical significance of rare variants causal for Mendelian and complex disorders.BMC medical genomics · 2018Article
- International Cooperation to Enable the Diagnosis of All Rare Genetic Diseases.American journal of human genetics · 2017Article
- When "Cold Spring Harbor molecular case studies · 2017Article
- Gene discovery for Mendelian conditions via social networking: de novo variants in KDM1A cause developmental delay and distinctive facial features.Genetics in medicine : official journal of the American College of Medical Genetics · 2016Article
- The Matchmaker Exchange: a platform for rare disease gene discovery.Human mutation · 2015Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Clinical sequencing is expanding, but causal variants are still not identified in the majority of cases. These unsolved cases can aid in gene discovery when individuals with similar phenotypes are identified in systems such as the Matchmaker Exchange. We describe risks for gene discovery in this growing set of unsolved cases. In a set of rare disease cases with the same phenotype, it is not difficult to find two individuals with the same phenotype that carry variants in the same gene. We quantify the risk of false-positive association in a cohort of individuals with the same phenotype, using the prior probability of observing a variant in each gene from over 60,000 individuals (Exome Aggregation Consortium). Based on the number of individuals with a genic variant, cohort size, specific gene, and mode of inheritance, we calculate a P value that the match represents a true association. A match in two of 10 patients in MECP2 is statistically significant (P = 0.0014), whereas a match in TTN would not reach significance, as expected (P > 0.999). Finally, we analyze the probability of matching in clinical exome cases to estimate the number of cases needed to identify genes related to different disorders. We offer Rare Disease Match, an online tool to mitigate the uncertainty of false-positive associations.
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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.