Title |
Guidelines for investigating causality of sequence variants in human disease
|
---|---|
Published in |
Nature, April 2014
|
DOI | 10.1038/nature13127 |
Pubmed ID | |
Authors |
D. G. MacArthur, T. A. Manolio, D. P. Dimmock, H. L. Rehm, J. Shendure, G. R. Abecasis, D. R. Adams, R. B. Altman, S. E. Antonarakis, E. A. Ashley, J. C. Barrett, L. G. Biesecker, D. F. Conrad, G. M. Cooper, N. J. Cox, M. J. Daly, M. B. Gerstein, D. B. Goldstein, J. N. Hirschhorn, S. M. Leal, L. A. Pennacchio, J. A. Stamatoyannopoulos, S. R. Sunyaev, D. Valle, B. F. Voight, W. Winckler, C. Gunter |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 87 | 31% |
United Kingdom | 29 | 10% |
Canada | 10 | 4% |
Spain | 9 | 3% |
Switzerland | 8 | 3% |
Japan | 7 | 2% |
Italy | 5 | 2% |
Netherlands | 4 | 1% |
Australia | 4 | 1% |
Other | 34 | 12% |
Unknown | 86 | 30% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 137 | 48% |
Scientists | 129 | 46% |
Science communicators (journalists, bloggers, editors) | 10 | 4% |
Practitioners (doctors, other healthcare professionals) | 7 | 2% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 43 | 2% |
United Kingdom | 21 | 1% |
Germany | 10 | <1% |
Spain | 9 | <1% |
Brazil | 7 | <1% |
France | 6 | <1% |
Italy | 6 | <1% |
South Africa | 5 | <1% |
Australia | 5 | <1% |
Other | 44 | 2% |
Unknown | 1845 | 92% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 477 | 24% |
Researcher | 474 | 24% |
Student > Master | 183 | 9% |
Student > Bachelor | 141 | 7% |
Other | 127 | 6% |
Other | 420 | 21% |
Unknown | 179 | 9% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 663 | 33% |
Biochemistry, Genetics and Molecular Biology | 489 | 24% |
Medicine and Dentistry | 348 | 17% |
Computer Science | 76 | 4% |
Neuroscience | 60 | 3% |
Other | 139 | 7% |
Unknown | 226 | 11% |