Detalle Publicación


Rare variants in PLD3 do not affect risk for early-onset Alzheimer disease in a European consortium cohort.

Autores: Cacace, R.; Van den Bossche, T.; Engelborghs, S.; Geerts, N.; Laureys, A.; Dillen, L.; Graff, C.; Thonberg, H.; Chiang, H.-H.; Pastor, P.; Ortega Cubero, Sara; Pastor, María A.; Diehl-Schmid, J.; Alexopoulos, P.; Benussi, L.; Ghidoni, R.; Binetti, G.; Nacmias, B.; Sorbi, S.; Sanchez-Valle, R.; Lladó, A.; Gelpi, E.; Almeida, M. R.; Santana, I.; Tsolaki, M.; Koutroumani, M.; Clarimon, J.; Lleó, A.; Fortea, J.; Mendonça, A. de; Martins, M.; Borroni, B.; Padovani, A.; Matej, R.; Rohan, Z.; Vandenbulcke, M.; Vandenberghe, R.; De Deyn, P. P.; Cras, P.; van der Zee, J.; Sleegers, K.; Van Broeckhoven, C.
Título de la revista: HUMAN MUTATION
ISSN: 1059-7794
Volumen: 36
Número: 12
Páginas: 1226 - 1235
Fecha de publicación: 2015
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.