Guidelines for investigating causality of sequence variants in human disease.

Nature
Authors
Keywords
Abstract

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.

Year of Publication
2014
Journal
Nature
Volume
508
Issue
7497
Pages
469-76
Date Published
2014 Apr 24
ISSN
1476-4687
URL
DOI
10.1038/nature13127
PubMed ID
24759409
PubMed Central ID
PMC4180223
Links
Grant list
R01 MH101810 / MH / NIMH NIH HHS / United States
R01 HG007022 / HG / NHGRI NIH HHS / United States
R01 HL117626 / HL / NHLBI NIH HHS / United States
U54 HG006997 / HG / NHGRI NIH HHS / United States
P30 DK020595 / DK / NIDDK NIH HHS / United States