dc.contributor.author | Curtis, D | en_US |
dc.date.accessioned | 2017-10-03T09:01:14Z | |
dc.date.available | 2017-08-01 | en_US |
dc.date.issued | 2018-01 | en_US |
dc.date.submitted | 2017-09-24T20:41:49.878Z | |
dc.identifier.uri | http://qmro.qmul.ac.uk/xmlui/handle/123456789/26403 | |
dc.description.abstract | Polygenic risk scores obtained as a weighted sum of associated variants can be used to explore association in additional data sets and to assign risk scores to individuals. The methods used to derive polygenic risk scores from common SNPs are not suitable for variants detected in whole exome sequencing studies. Rare variants, which may have major effects, are seen too infrequently to judge whether they are associated and may not be shared between training and test subjects. A method is proposed whereby variants are weighted according to their frequency, their annotations and the genes they affect. A weighted sum across all variants provides an individual risk score. Scores constructed in this way are used in a weighted burden test and are shown to be significantly different between schizophrenia cases and controls using a five-way cross-validation procedure. This approach represents a first attempt to summarise exome sequence variation into a summary risk score, which could be combined with risk scores from common variants and from environmental factors. It is hoped that the method could be developed further. | en_US |
dc.description.sponsorship | NIMH. Grant Number: R01MH077139
Sylvan C. Herman Foundation
Stanley Medical Research Institute
Swedish Research Council. Grant Numbers: 2009–4959, 2011–4659, RCMH089905 | en_US |
dc.format.extent | 11 - 22 | en_US |
dc.language | eng | en_US |
dc.language.iso | en | en_US |
dc.relation.ispartof | Ann Hum Genet | en_US |
dc.rights | "This is the peer reviewed version of the following article: Curtis, D. (2017), Construction of an Exome-Wide Risk Score for Schizophrenia Based on a Weighted Burden Test. Annals of Human Genetics. doi:10.1111/ahg.12212 which has been published in final form at https://doi.org/10.1111/ahg.12212 . This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving." | |
dc.subject | Association | en_US |
dc.subject | exome | en_US |
dc.subject | schizophrenia | en_US |
dc.subject | Case-Control Studies | en_US |
dc.subject | Exome | en_US |
dc.subject | Genetic Predisposition to Disease | en_US |
dc.subject | Humans | en_US |
dc.subject | Models, Genetic | en_US |
dc.subject | Multifactorial Inheritance | en_US |
dc.subject | Risk | en_US |
dc.subject | Schizophrenia | en_US |
dc.subject | Sequence Analysis, DNA | en_US |
dc.title | Construction of an Exome-Wide Risk Score for Schizophrenia Based on a Weighted Burden Test. | en_US |
dc.type | Article | |
dc.identifier.doi | 10.1111/ahg.12212 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/28895126 | en_US |
pubs.issue | 1 | en_US |
pubs.notes | 12 months | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 82 | en_US |
dcterms.dateAccepted | 2017-08-01 | en_US |