: Return 1701

Notes

We have called CNVs in the full UK Biobank. 488,423 individual CEL files were downloaded in 2016 and 2017. They were analysed with Affymetrix Powertools, followed by PennCNV.
All the methods are detailed in the supplementary information of our first paper: Kendall K, Rees E, Escott-Price V, Einon M, ThomasR, Hewitt J, C O Donovan MC, Owen MJ, Walters J, Kirov G.
Cognitive performance among carriers of pathogenic copy number variants: Analysis of 152,000 UK Biobank subjects. Biol Psychiatry, 2017, 82(2), 103 110.
The 92 Pathogenic CNVs loci have been checked, however the remaining CNVs have not been examined, so there are likely to be false-positives.

Application 14421

Identifying the spectrum of biomedical traits in adults with pathogenic copy number variants (CNVs)

Deletions and duplications of large stretches of chromosomes, known as copy number variants (CNVs), cause several neurodevelopmental disorders, such as schizophrenia, developmental delay and autism spectrum disorder. However, the full clinical spectrum associated with most of these CNVs has not yet been established and there is limited evidence of the impact of these CNVs in the general population, e.g. in apparently healthy carriers. We propose to identify the carriers of pathogenic CNVs in the full UK Biobank sample. We will then identify the cognitive deficits and common medical problems that are increased in carriers of each of these CNVs. The rarity of most pathogenic CNVs has so far prevented researchers from confidently establishing their full medical and neurocognitive consequences. Therefore it is currently impossible for genetic counsellors to give accurate advice to CNV carriers. Our research will provide the most comprehensive assessment of neuropsychiatric and common medical problems associated with known pathogenic CNVs. This will result in a greater understanding of the risks conferred by these CNVs for the development of diseases, and give clinicians the necessary information for diagnosing, counselling and treating the carriers of these CNVs. We will first generate a set of high quality CNVs from all participants in the UK Biobank cohort using the data from microarray genotyping already conducted by Affymetrix. (If UK Biobank calls the CNVs centrally, we can use these calls and just apply our quality control filtering). We will identify the individuals carrying pathogenic CNVs. Carriers of pathogenic CNVs will then be compared with the remaining participants, who are free of such CNVs, for neuropsychiatric problems (including cognitive performance), common medical conditions, and basic characteristics (e.g. weight and height), which can be affected by CNVs. We require genetic data from the full UK Biobank cohort. We also need a set of basic demographic and common health outcomes that could be affected by CNVs. These include neuropsychiatric outcomes such as epilepsy, psychosis, mood disorders, cognitive tests, educational indices, and self-reported medical/psychiatric conditions. When it becomes available, we would like to add the diagnostic codes from the primary care data, to supplement the self-reports. Carriers of these CNVs might have an increased rate of premature terminations and have fewer children, therefore we also want to collect the self-reported information on these outcomes.

Lead investigator:	Professor George Kirov
Lead institution:	Cardiff University

2 related Returns

Return ID	App ID	Description	Archive Date
783	14421	Cognitive performance among carriers of pathogenic copy number variants: Analysis of 152,000 UK Biobank subjects	17 Oct 2017
3444	14421	Medical and neurobehavioural phenotypes in carriers of X-linked ichthyosis-associated genetic deletions in the UK Biobank	25 May 2021

1 Publication

Pub ID	Title	Author(s)	Year	Journal
1702	Medical consequences of pathogenic CNVs in adults: analysis of the UK Biobank	Crawford K et al.	2019	J Med Genet

Application:	14421, Identifying the spectrum of biomedical traits in adults with pathogenic copy number variants (CNVs)
Title:	Medical consequences of pathogenic CNVs in adults: analysis of the UK Biobank
Size:	75.6 MB
Archived:	12 Aug 2019
Stability:	Updateable
Personal:	Contains individual-level data