| Title: | Association of congenital cardiovascular malformation and neuropsychiatric phenotypes with 15q11.2 (BP1-BP2) deletion in the UK Biobank |
| Journal: | European Journal of Human Genetics |
| Published: | 23 Apr 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/32327713/ |
| DOI: | https://doi.org/10.1038/s41431-020-0626-8 |
| URL: | https://www.nature.com/articles/s41431-020-0626-8.pdf |
Publication 4185
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Abstract
Deletion of a non-imprinted 500kb genomic region at chromosome 15q11.2, between breakpoints 1 and 2 of the Prader-Willi/Angelman locus (BP1-BP2 deletion), has been associated in previous studies with phenotypes including congenital cardiovascular malformations (CVM). Previous studies investigating association between BP1-BP2 deletion and CVM have tended to recruit cases with rarer and more severe CVM phenotypes; the impact of CVM on relatively unselected population cohorts, anticipated to contain chiefly less severe but commoner CHD phenotypes, is relatively unexplored. More precisely defining the impact of BP1-BP2 deletion on CVM risk could be useful to guide genetic counselling, since the deletion is frequently identified in the neurodevelopmental clinic. Using the UK Biobank (UKB) cohort of ~500,000 individuals, we identified individuals with CVM and investigated the association with deletions at the BP1-BP2 locus. In addition, we assessed the association of BP1-BP2 deletions with neuropsychiatric diagnoses, cognitive function and academic achievement. Cases of CVM had an increased prevalence of the deletion compared with controls (0.64%; OR = 1.73 [95% CI 1.08-2.75]; p = 0.03), as did those with neuropsychiatric diagnoses (0.68%; OR = 1.84 [95% CI 1.23-2.75]; p = 0.004). We conclude that BP1-BP2 deletion moderately increases the risk of the generally milder, but commoner, CVM phenotypes seen in this unselected population, in addition to its previously demonstrated association in case/control studies ascertained for CVM.</p>
10 Authors
- Simon G. Williams
- Apostol Nakev
- Hui Guo
- Simon Frain
- Gennadiy Tenin
- Anna Liakhovitskaia
- Priyanka Saha
- James R. Priest
- Kathryn E. Hentges
- Bernard D. Keavney
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