Deletions at 22q11.2 in idiopathic Parkinson's disease: a combined analysis of genome-wide association data

Mok, Kin Y., Sheerin, Una, Simón-Sánchez, Javier, Salaka, Afnan, Chester, Lucy, Escott-Price, Valentina ORCID: https://orcid.org/0000-0003-1784-5483, Mantripragada, Kiran ORCID: https://orcid.org/0000-0003-2070-8105, Doherty, Karen M., Noyce, Alastair J., Mencacci, Niccolo E., Lubbe, Steven J., Williams-Gray, Caroline H., Barker, Roger A., van Dijk, Karin D., Berendse, Henk W., Heutink, Peter, Corvol, Jean-Christophe, Cormier, Florence, Lesage, Suzanne, Brice, Alexis, Brockmann, Kathrin, Schulte, Claudia, Gasser, Thomas, Foltynie, Thomas, Limousin, Patricia, Morrison, Karen E., Clarke, Carl E., Sawcer, Stephen, Warner, Tom T., Lees, Andrew J., Morris, Huw R., Nalls, Mike A., Singleton, Andrew B., Hardy, John, Abramov, Andrey Y., Plagnol, Vincent, Williams, Nigel M. ORCID: https://orcid.org/0000-0003-1177-6931 and Wood, Nicholas W. 2016. Deletions at 22q11.2 in idiopathic Parkinson's disease: a combined analysis of genome-wide association data. Lancet Neurology 15 (6) , pp. 585-596. 10.1016/S1474-4422(16)00071-5

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Abstract

Parkinson's disease has been reported in a small number of patients with chromosome 22q11.2 deletion syndrome. In this study, we screened a series of large, independent Parkinson's disease case-control studies for deletions at 22q11.2. Methods We used data on deletions spanning the 22q11.2 locus from four independent case-control Parkinson's disease studies (UK Wellcome Trust Case Control Consortium 2, Dutch Parkinson's Disease Genetics Consortium, US National Institute on Aging, and International Parkinson's Disease Genomics Consortium studies), which were independent of the original reports of chromosome 22q11.2 deletion syndrome. We did case-control association analysis to compare the proportion of 22q11.2 deletions found, using the Fisher's exact test for the independent case-control studies and the Mantel-Haenszel test for the meta-analyses. We retrieved clinical details of patients with Parkinson's disease who had 22q11.2 deletions from the medical records of these patients. Findings We included array-based copy number variation data from 9387 patients with Parkinson's disease and 13 863 controls. Eight patients with Parkinson's disease and none of the controls had 22q11.2 deletions (p=0·00082). In the 8451 patients for whom age at onset data were available, deletions at 22q11.2 were associated with Parkinson's disease age at onset (Mann-Whitney U test p=0·001). Age at onset of Parkinson's disease was lower in patients carrying a 22q11.2 deletion (median 37 years, 95% CI 32·0–55·5; mean 42·1 years [SD 11·9]) than in those who did not carry a deletion (median 61 years, 95% CI 60·5–61·0; mean 60·3 years [SD 12·8]). A 22q11.2 deletion was present in more patients with early-onset (p<0·0001) and late-onset Parkinson's disease (p=0·016) than in controls, and in more patients with early-onset than late-onset Parkinson's disease (p=0·005). Interpretation Clinicians should be alert to the possibility of 22q11.2 deletions in patients with Parkinson's disease who have early presentation or features associated with the chromosome 22q11.2 deletion syndrome, or both.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Advanced Research Computing @ Cardiff (ARCCA) Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Additional Information:	International Parkinson's Disease Genomics Consortium (IPDGC). This is an open access article distributed under the terms of the CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium. You are not required to obtain permission to reuse this article content, provided that you credit the author and journal.
Publisher:	Elsevier
ISSN:	1474-4422
Date of First Compliant Deposit:	5 July 2016
Date of Acceptance:	1 February 2016
Last Modified:	03 May 2023 20:56
URI:	https://orca.cardiff.ac.uk/id/eprint/92332

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