Kaplanis, J;
Samocha, KE;
Wiel, L;
Zhang, Z;
Arvai, KJ;
Eberhardt, RY;
Gallone, G;
... Retterer, K; + view all
(2020)
Evidence for 28 genetic disorders discovered by combining healthcare and research data.
Nature
, 586
(7831)
pp. 757-762.
10.1038/s41586-020-2832-5.
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Abstract
De novo mutations in protein-coding genes are a well-established cause of developmental disorders1. However, genes known to be associated with developmental disorders account for only a minority of the observed excess of such de novo mutations1,2. Here, to identify previously undescribed genes associated with developmental disorders, we integrate healthcare and research exome-sequence data from 31,058 parent-offspring trios of individuals with developmental disorders, and develop a simulation-based statistical test to identify gene-specific enrichment of de novo mutations. We identified 285 genes that were significantly associated with developmental disorders, including 28 that had not previously been robustly associated with developmental disorders. Although we detected more genes associated with developmental disorders, much of the excess of de novo mutations in protein-coding genes remains unaccounted for. Modelling suggests that more than 1,000 genes associated with developmental disorders have not yet been described, many of which are likely to be less penetrant than the currently known genes. Research access to clinical diagnostic datasets will be critical for completing the map of genes associated with developmental disorders.
| Type: | Article |
|---|---|
| Title: | Evidence for 28 genetic disorders discovered by combining healthcare and research data |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41586-020-2832-5 |
| Publisher version: | https://doi.org/10.1038/s41586-020-2832-5 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions. |
| Keywords: | Cohort Studies, DNA Copy Number Variations, DNA Mutational Analysis, Data Analysis, Databases, Genetic, Datasets as Topic, Delivery of Health Care, Developmental Disabilities, Europe, Female, Genetic Diseases, Inborn, Germ-Line Mutation, Haploinsufficiency, Humans, Male, Mutation, Missense, Penetrance, Perinatal Death, Sample Size |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10133185 |
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