Systematic Analysis of Candidate Genes for Alzheimer's Disease in a French, Genome-Wide Association Study

Article type: Research Article

Authors: Laumet, Geoffroy^{a; b; c} | Chouraki, Vincent^{a; b; c} | Grenier-Boley, Benjamin^{a; b; c} | Legry, Vanessa^{a; b; c} | Heath, Simon^d | Zelenika, Diana^d | Fievet, Nathalie^{a; b} | Hannequin, Didier^e | Delepine, Marc^d | Pasquier, Florence^{c; f} | Hanon, Olivier^g | Brice, Alexis^h | Epelbaum, Jacques^g | Berr, Claudineⁱ | Dartigues, Jean-Francois^j | Tzourio, Christophe^{k; l} | Campion, Dominique^e | Lathrop, Mark^{d; m} | Bertram, Larsⁿ | Amouyel, Philippe^{a; b; c; f} | Lambert, Jean-Charles^{a; b; c; *}

Affiliations: [a] INSERM U744, Lille, France | [b] Institut Pasteur de Lille, Lille, France | [c] Université de Lille Nord de France, Lille, France | [d] Centre National de Génotypage, Institut Génomique, Commissariat à l'Energie Atomique, Evry, France | [e] INSERM U614, Faculté de Médecine-Pharmacie de Rouen, Rouen, France | [f] CHRU de Lille, Lille, France | [g] UMR 894, Inserm Faculté de Médecine, Université Paris Descartes, Paris, France | [h] Inserm, UMR_S679, Hôpital de la Salpêtrière, Paris, France | [i] INSERM U888, Hôpital La Colombière, Montpellier, France | [j] INSERM U897, Victor Segalen University, Bordeaux, France | [k] INSERM U708, Paris, France | [l] UPMC Univ Paris 06, Paris, France | [m] Fondation Jean Dausset- CEPH, Paris, France | [n] Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max-Planck Institute for Molecular Genetics, Berlin, Germany

Correspondence: [*] Correspondence to: Jean-Charles Lambert, Unité INSERM 744, Institut Pasteur de Lille, BP 245, 1, rue du professeur Calmette, F-59019 Lille cedex, France. Tel.: +33 (0)3 20 87 73 91; Fax: +33 (0)3 20 87 78 94; E-mail: [email protected].

Note: [] Handling Associate Editor: Daniela Galimberti

Abstract: We selected twenty genes from the "Top Results" list on the AlzGene database website and assessed their association with risk of developing Alzheimer's disease (AD) in a large, genome-wide association study (using 526 SNPs from 2,032 AD cases and 5,328 controls) performed in France. The APOE, CLU, PICALM, and CR1 loci were excluded, since they had already been extensively analyzed. Ten genes/loci (TFAM, SORL1, CHRNB2, SORCS1, DAPK1, MTHFR, GWA 14q32.13, BDNF, NEDD9, and CH25H) showed weak nominal association with AD risk, in line with previous studies. In the remaining ten genes/loci (TNK1, ACE, CST3, IL1B, hCG2039140, PRNP, GAB2, LOC651924, IL1A, and TF), no single nucleotide polymorphisms were associated in our dataset. Of the genes showing nominal association in our cohorts, TFAM and CHRNB2 appear particularly interesting and warrant further genetic and functional follow-up analyses.

Keywords: AlzGene database, Alzheimer's disease, association, GWAS, replication, risk factor, SNPs

DOI: 10.3233/JAD-2010-100126

Journal: Journal of Alzheimer's Disease, vol. 20, no. 4, pp. 1181-1188, 2010