Scientific Publications

Guidelines for investigating causality of sequence variants in human disease.

Publication TypeJournal Article
AuthorsMacarthur, DG, Manolio TA, Dimmock DP, Rehm HL, Shendure J., Abecasis GR, Adams DR, Altman RB, Antonarakis SE, Ashley EA, Barrett JC, Biesecker LG, Conrad DF, Cooper GM, Cox NJ, Daly M. J., Gerstein MB, Goldstein DB, Hirschhorn JN, Leal SM, Pennacchio LA, Stamatoyannopoulos JA, Sunyaev SR, Valle D., Voight BF, Winckler W., and Gunter C.
AbstractThe 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 Publication2014
JournalNature
Volume508
Issue7497
Pages469-76
Date Published (YYYY/MM/DD)2014/04/24
ISSN Number0028-0836
DOI10.1038/nature13127
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/24759409?dopt=Abstract