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Title
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Rare variants in PLD3 do not affect risk for early-onset Alzheimer disease in a European consortium cohort
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Author
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Institution/Organisation
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Belgium Neurology BELNEU Consortiu
European Early-Onset Dementia EU E
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Abstract
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| Rare variants in the phospholipase D3 gene (PLD3) were associated with increased risk for late-onset Alzheimer disease (LOAD). We identified a missense mutation in PLD3 in whole-genome sequence data of a patient with autopsy confirmed Alzheimer disease (AD) and onset age of 50 years. Subsequently, we sequenced PLD3 in a Belgian early-onset Alzheimer disease (EOAD) patient (N=261) and control (N=319) cohort, as well as in European EOAD patients (N=946) and control individuals (N=1,209) ascertained in different European countries. Overall, we identified 22 rare variants with a minor allele frequency <1%, 20 missense and two splicing mutations. Burden analysis did not provide significant evidence for an enrichment of rare PLD3 variants in EOAD patients in any of the patient/control cohorts. Also, meta-analysis of the PLD3 data, including a published dataset of a German EOAD cohort, was not significant (P=0.43; OR=1.53, 95% CI 0.60-3.31). Consequently, our data do not support a role for PLD3 rare variants in the genetic etiology of EOAD in European EOAD patients. Our data corroborate the negative replication data obtained in LOAD studies and therefore a genetic role of PLD3 in AD remains to be demonstrated. Published 2015 Wiley Periodicals, Inc. |
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Language
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English
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Source (journal)
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Human mutation. - New York, N.Y.
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Publication
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New York, N.Y.
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2015
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ISSN
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1059-7794
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DOI
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10.1002/HUMU.22908
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Volume/pages
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36
:12
(2015)
, p. 1226-1235
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ISI
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000364788500015
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Pubmed ID
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26411346
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Full text (Publisher's DOI)
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Full text (open access)
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