Guidelines for investigating causality of sequence variants in human disease

MacArthur, D G; Manolio, T A; Dimmock, D P; Rehm, H L; Shendure, J; Abecasis, G R; Adams, D R; Altman, R B; Antonarakis, Stylianos; Ashley, E A; Barrett, J C; Biesecker, L G; Conrad, D F; Cooper, G M; Cox, N J; Daly, M J; Gerstein, M B; Goldstein, D B; Hirschhorn, J N; Leal, S M; Pennacchio, L A; Stamatoyannopoulos, J A; Sunyaev, S R; Valle, D; Voight, B F; Winckler, W; Gunter, C

doi:10.1038/nature13127

Scientific article

English

Guidelines for investigating causality of sequence variants in human disease

Published in

Nature, vol. 508, no. 7497, p. 469-476

Publication date

2014

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.

Keywords

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

UNIGE affiliation entities

Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement

UNIGE research groups

Pathologie Moléculaire de la Trisomie 21 et le Génome Humain (248)

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

Article (Published version)

Identifiers

PID : unige:42274
DOI : 10.1038/nature13127
PMID : 24759409

Journal ISSN

0028-0836

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26/11/2014 16:11:00

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14/03/2023 22:18:43

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Guidelines for investigating causality of sequence variants in human disease

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