Title :

Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease

Author(s) :

Lambert, J-C [Auteur]
Institut Pasteur de Lille
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Grenier-Boley, B [Auteur]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Harold, D [Auteur]
School of Medicine [Cardiff]
Zelenika, D [Auteur]
Centre National de Génotypage [CNG]
Chouraki, V [Auteur]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Kamatani, Y [Auteur]
Centre d'Etude du Polymorphisme Humain [CEPH]
Centre National de Génotypage [CNG]
Sleegers, K [Auteur]
University of Antwerp [UA]
Ikram, M [Auteur]
Erasmus University Medical Center [Rotterdam] [Erasmus MC]
Hiltunen, M [Auteur]
Kuopio University Hospital [KUH]
University of Eastern Finland
Reitz, C [Auteur]
Columbia University [New York]
Mateo, I [Auteur]
Universidad de Cantabria [Santander] = University of Cantabria [Spain] = Université de Cantabrie [Espagne] [UC / UniCan]
Feulner, T [Auteur]
Universität des Saarlandes [Saarbrücken]
Bullido, M [Auteur]
Universidad Autónoma de Madrid [UAM]
Centro de Biología Molecular Severo Ochoa [Madrid] [CBMSO]
Galimberti, D [Auteur]
Università degli Studi di Milano = University of Milan [UNIMI]
Centro Dino Ferrari [Milano]
Concari, L [Auteur]
Università degli studi di Parma = University of Parma [UNIPR]
Alvarez, V [Auteur]
Hospital Universitario Central de Asturias [HUCA]
Sims, R [Auteur]
Cardiff University
Gerrish, A [Auteur]
Cardiff University
Chapman, J [Auteur]
Cardiff University
Deniz-Naranjo, C [Auteur]
Hospital Universitario de Gran Canaria Dr Negrin
Solfrizzi, V [Auteur]
Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro [UNIBA]
Sorbi, S [Auteur]
Università degli Studi di Firenze = University of Florence = Université de Florence [UniFI]
Arosio, B [Auteur]
Università degli Studi di Milano = University of Milan [UNIMI]
Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
Spalletta, G [Auteur]
Fondazione Santa Lucia [IRCCS]
Siciliano, G [Auteur]
University of Pisa [Italy] = Università di Pisa [Italia] = Université de Pise [Italie] [UniPi]
Epelbaum, J [Auteur]
Centre de Psychiatrie et Neurosciences [U894]
Hannequin, D [Auteur]
Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques
Dartigues, J-F [Auteur]
Epidémiologie et Biostatistique [Bordeaux]
Tzourio, C [Auteur]
Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie [UPMC]
Neuroépidémiologie
Berr, C [Auteur]
Hôpital la Colombière [CHU Montpellier]
Neuropsychiatrie : recherche épidémiologique et clinique [PSNREC]
Schrijvers, Emc [Auteur]
Erasmus University Medical Center [Rotterdam] [Erasmus MC]
Rogers, R [Auteur]
Columbia University [New York]
Tosto, G [Auteur]
Columbia University [New York]
Pasquier, F [Auteur]
Université Lille Nord de France (COMUE)
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Bettens, K [Auteur]
University of Antwerp [UA]
van Cauwenberghe, C [Auteur]
University of Antwerp [UA]
Fratiglioni, L [Auteur]
Stockholm University
Karolinska University Hospital [Stockholm]
Aging Research Center [Karolinska Institutet] [ARC ]
Graff, C [Auteur]
Karolinska Institutet [Stockholm]
Karolinska University Hospital [Stockholm]
Delepine, M [Auteur]
Institut de Génomique d'Evry [IG]
Centre National de Génotypage [CNG]
Ferri, R [Auteur]
"Oasi Maria Santissima" Institute for Research and Prevention of Mental Retardation [I.R.C.C.S.]
Reynolds, C [Auteur]
University of California [Riverside] [UC Riverside]
Lannfelt, L [Auteur]
Uppsala University
Ingelsson, M [Auteur]
Uppsala University
Prince, J [Auteur]
Karolinska Institute
Chillotti, C [Auteur]
Pilotto, A [Auteur]
Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo] [IRCCS]
Seripa, D [Auteur]
Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo] [IRCCS]
Boland, A [Auteur]
Centre National de Génotypage [CNG]
Institut de Génomique d'Evry [IG]
Mancuso, M [Auteur]
University of Pisa [Italy] = Università di Pisa [Italia] = Université de Pise [Italie] [UniPi]
Bossù, P [Auteur]
Fondazione Santa Lucia [IRCCS]
Annoni, G [Auteur]
Università degli Studi di Milano = University of Milan [UNIMI]
Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
Nacmias, B [Auteur]
Università degli Studi di Firenze = University of Florence = Université de Florence [UniFI]
Bosco, P [Auteur]
"Oasi Maria Santissima" Institute for Research and Prevention of Mental Retardation [I.R.C.C.S.]
Panza, F [Auteur]
Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro [UNIBA]
Sanchez-Garcia, F [Auteur]
Hospital Universitario de Gran Canaria Dr Negrin
del Zompo, M [Auteur]
University of Cagliari
Coto, E [Auteur]
Hospital Universitario Central de Asturias [HUCA]
Owen, M [Auteur]
Cardiff University
O'Donovan, M [Auteur]
Cardiff University
Valdivieso, F [Auteur]
Universidad Autónoma de Madrid [UAM]
Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas [CIBERNED]
Centro de Biología Molecular Severo Ochoa [Madrid] [CBMSO]
Caffara, P [Auteur]
Università degli studi di Parma = University of Parma [UNIPR]
Scarpini, E [Auteur]
Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
Università degli Studi di Milano = University of Milan [UNIMI]
Combarros, O [Auteur]
Universidad de Cantabria [Santander] = University of Cantabria [Spain] = Université de Cantabrie [Espagne] [UC / UniCan]
Buée, L [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Campion, D [Auteur]
Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques
Soininen, H [Auteur]
Kuopio University Hospital [KUH]
University of Eastern Finland
Breteler, M [Auteur]
Dendrite Differenciation Group [DZNE - Bonn]
Erasmus University Medical Center [Rotterdam] [Erasmus MC]
Riemenschneider, M [Auteur]
Universität des Saarlandes [Saarbrücken]
van Broeckhoven, C [Auteur]
University of Antwerp [UA]
Alpérovitch, A [Auteur]
Neuroépidémiologie
Lathrop, M [Auteur]
Fondation Jean Dausset CEPH
Centre National de Génotypage [CNG]
Trégouët, D-A [Auteur]
Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] [IHU ICAN]
Cardiovascular Genomics
Williams, J [Auteur]
Cardiff University
Amouyel, P [Auteur]
Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Institut Pasteur de Lille

Journal title :

Molecular Psychiatry

Pages :

461-470

Publisher :

Nature Publishing Group

Publication date :

2012-03-20

ISSN :

1359-4184

English keyword(s) :

Alzheimer
amyloid
FRMD4A
GWAS
plasma
Alzheimer amyloid FRMD4A GWAS plasma

HAL domain(s) :

Sciences du Vivant [q-bio]
Sciences du Vivant [q-bio]/Génétique/Génétique humaine
Sciences du Vivant [q-bio]/Neurosciences [q-bio.NC]

English abstract : [en]

Recently, several genome-wide association studies (GWASs) have led to the discovery of nine new loci of genetic susceptibility in Alzheimer's disease (AD). However, the landscape of the AD genetic susceptibility is far ...
Show more >Recently, several genome-wide association studies (GWASs) have led to the discovery of nine new loci of genetic susceptibility in Alzheimer's disease (AD). However, the landscape of the AD genetic susceptibility is far away to be complete and in addition to single-SNP (single-nucleotide polymorphism) analyses as performed in conventional GWAS, complementary strategies need to be applied to overcome limitations inherent to this type of approaches. We performed a genome-wide haplotype association (GWHA) study in the EADI1 study (n=2025 AD cases and 5328 controls) by applying a sliding-windows approach. After exclusion of loci already known to be involved in AD (APOE, BIN1 and CR1), 91 regions with suggestive haplotype effects were identified. In a second step, we attempted to replicate the best suggestive haplotype associations in the GERAD1 consortium (2820 AD cases and 6356 controls) and observed that 9 of them showed nominal association. In a third step, we tested relevant haplotype associations in a combined analysis of five additional case–control studies (5093 AD cases and 4061 controls). We consistently replicated the association of a haplotype within FRMD4A on Chr.10p13 in all the data set analyzed (OR: 1.68; 95% CI: (1.43–1.96); P=1.1 × 10−10). We finally searched for association between SNPs within the FRMD4A locus and Aβ plasma concentrations in three independent non-demented populations (n=2579). We reported that polymorphisms were associated with plasma Aβ42/Aβ40 ratio (best signal, P=5.4 × 10−7). In conclusion, combining both GWHA study and a conservative three-stage replication approach, we characterised FRMD4A as a new genetic risk factor of AD.Show less >

Language :

Anglais

Popular science :

Non

Comment :

Erratum: Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease. Mol Psychiatry 18, 521 (2013) : Following the online publication of this article, the authors noted an error in Dr Caffarra's name. The complete and correct author name is P Caffarra.

Collections :

• Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement (RID-AGE) - U1167

Source :

Harvested from HAL