No replication of genetic association between candidate polymorphisms and Alzheimer's disease.
Alzheimer's disease is a genetically complex disorder, for which new putative susceptibility genes are constantly proposed in the literature. We selected 16 candidate genes involved in biological pathways closely related to the pathology, and for which a genetic association with Alzheimer's disease was previously detected: ACE, BACE1, BDNF, ECE1, HSPG2, IDE, IL1a, IL6, IL10, MAPT, PLAU, PrnP, PSEN1, SORL1, TFCP2 and TGFb1. The variants originally associated with the disease were genotyped in a French Caucasian sample including 428 cases and 475 controls and tested for association in order to replicate the initial results. Despite a careful replication study design, we failed to validate the initial findings for any of these variants, with the possible exception of MAPT, SORL1 and TFCP2 for which some nominal but inconsistent evidence of association was observed.
Cousin
Emmanuelle
E
Biological Sciences Department, sanofi-aventis Recherche et Développement, Centre de Génétique humaine, 91057 Evry, France.
Macé
Sandrine
S
Rocher
Corinne
C
Dib
Colette
C
Muzard
Gaëlle
G
Hannequin
Didier
D
Pradier
Laurent
L
Deleuze
Jean-François
JF
Génin
Emmanuelle
E
Brice
Alexis
A
Campion
Dominique
D
D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D030541:Databases, Genetic; D005602:France / Q000453:epidemiology; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D055106:Genome-Wide Association Study / Q000592:standards*; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D019683:Penetrance; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044465:White People / Q000235:genetics