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- Dokumenttyp:
- Journal Article; Research Support, Non-U.S. Gov't; Journal Article
- Autor(en):
- Titel:
- Rare Variants in PLD3 Do Not Affect Risk for Early-Onset Alzheimer Disease in a European Consortium Cohort.
- Abstract:
- 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.
- Zeitschriftentitel:
- Hum Mutat
- Jahr:
- 2015
- Band / Volume:
- 36
- Heft / Issue:
- 12
- Seitenangaben Beitrag:
- 1226-35
- Sprache:
- eng
- Volltext / DOI:
- doi:10.1002/humu.22908
- PubMed:
- http://view.ncbi.nlm.nih.gov/pubmed/26411346
- Print-ISSN:
- 1059-7794
- TUM Einrichtung:
- Klinik und Poliklinik für Psychiatrie und Psychotherapie
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