Scientific article
Open access

Guidelines for investigating causality of sequence variants in human disease

Published inNature, vol. 508, no. 7497, p. 469-476
Publication date2014

The discovery of rare genetic variants is accelerating, and clear guidelines for distinguishing disease-causing sequence variants from the many potentially functional variants present in any human genome are urgently needed. Without rigorous standards we risk an acceleration of false-positive reports of causality, which would impede the translation of genomic research findings into the clinical diagnostic setting and hinder biological understanding of disease. Here we discuss the key challenges of assessing sequence variants in human disease, integrating both gene-level and variant-level support for causality. We propose guidelines for summarizing confidence in variant pathogenicity and highlight several areas that require further resource development.

  • Disease
  • False Positive Reactions
  • Genes/genetics
  • Genetic Predisposition to Disease/genetics
  • Genetic Variation/genetics
  • Guidelines as Topic
  • Humans
  • Information Dissemination
  • Publishing
  • Reproducibility of Results
  • Research Design
  • Translational Medical Research/standards
Citation (ISO format)
MACARTHUR, D G et al. Guidelines for investigating causality of sequence variants in human disease. In: Nature, 2014, vol. 508, n° 7497, p. 469–476. doi: 10.1038/nature13127
Main files (1)
Article (Published version)
ISSN of the journal0028-0836

Technical informations

Creation11/26/2014 4:11:00 PM
First validation11/26/2014 4:11:00 PM
Update time03/14/2023 10:18:43 PM
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