| Application: | 14421, Identifying the spectrum of biomedical traits in adults with pathogenic copy number variants (CNVs) |
| Title: | Cognitive performance among carriers of pathogenic copy number variants: Analysis of 152,000 UK Biobank subjects |
| Size: | 2.4 MB |
| Archived: | 17 Oct 2017 |
| Stability: | Complete |
| Personal: | Contains individual-level data |
Return 783
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Notes
We used Affymetrix Power Tools and PennCNV-Affy software to analyze Affymetrix microarrays of the first 152,728 genotyped individuals. We annotated a list of 93 CNVs and compared their frequencies with control datasets. We analyzed the performance on seven cognitive tests of carriers of 12 CNVs associated with schizophrenia (n 5 1087) and of carriers of another 41 neurodevelopmental CNVs (n 5 484). The frequencies of the 93 CNVs in the Biobank subjects were remarkably similar to those among 26,628 control subjects from other datasets. Carriers of schizophrenia-associated CNVs and of the group of 41 other neurodevelopmental CNVs had impaired performance on the cognitive tests, with nine of 14 comparisons remaining statistically significant after correction for multiple testing. They also had lower educational and occupational attainment (p values between 1027 and 10218). The deficits in cognitive performance were modest (Z score reductions between 0.01 and 0.51), compared with individuals with schizophrenia in the Biobank (Z score reductions between 0.35 and 0.90). This is the largest study on the cognitive phenotypes of CNVs to date. Adult carriers of neurodevelopmental CNVs from the general population have significant cognitive deficits. The UK Biobank will allow unprecedented opportunities for analysis of further phenotypic consequences of CNVs.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 |
|---|---|---|---|
| 3444 | 14421 | Medical and neurobehavioural phenotypes in carriers of X-linked ichthyosis-associated genetic deletions in the UK Biobank | 25 May 2021 |
| 1701 | 14421 | Medical consequences of pathogenic CNVs in adults: analysis of the UK Biobank | 12 Aug 2019 |
1 Publication
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 784 | Cognitive Performance Among Carriers of Pathogenic Copy Number Variants: Analysis of 152,000 UK Biobank Subjects | Kimberley M. Kendall (+9) | 2016 | Biological Psychiatry |
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