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Systematic Analysis of Candidate Genes for Alzheimer's Disease in a French, Genome-Wide Association Study
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.
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“An association of CH25H with AD was first reported in a hippocampal microarray study of AD brain tissue [53] and further suggested by an AlzGene meta-analysis for a sporadic AD population [54] and other AD patient-based independent systematic analyses [55–57].”
From 25-Hydroxycholesterol amplifies microglial IL-1β production in an apoE isoform-dependent manner (2020) · cites this paper as [57]
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Targeted capture and massively parallel sequencing of 12 human exomes
Ng, S. B., Turner, E. H., Robertson, P. D., Flygare, S. D., Bigham, A. W., Lee, C., Shaffer, T., Wong, M., Bhattacharjee, A., Eichler, E. E., et al. (2009) · Nature · doi:10.1038/nature08250 · Cited by 2,030
Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database
Bertram, L., McQueen, M. B., Mullin, K., Blacker, D., & Tanzi, R. E. (2007) · Nature Genetics · doi:10.1038/ng1934 · Cited by 1,857
Self-citationThe effects of human population structure on large genetic association studies
Marchini, J., Cardon, L. R., Phillips, M. S., & Donnelly, P. (2004) · Nature Genetics · doi:10.1038/ng1337 · Cited by 869
Clayton, D. G., Walker, N. M., Smyth, D. J., Pask, R., Cooper, J. D., Maier, L. M., Smink, L. J., Lam, A. C., Ovington, N. R., Stevens, H. E., et al. (2005) · Nature Genetics · doi:10.1038/ng1653 · Cited by 526
Genetic Control of Human Brain Transcript Expression in Alzheimer Disease
Webster, J. A., Gibbs, J. R., Clarke, J., Ray, M., Zhang, W., Holmans, P., Rohrer, K., Zhao, A., Marlowe, L., Kaleem, M., et al. (2009) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2009.03.011 · Cited by 304
Examination of the current top candidate genes for AD in a genome-wide association study
Feulner, T. M., Laws, S. M., Friedrich, P., Wagenpfeil, S., Wurst, S. H. R., Riehle, C., Kuhn, K. A., Krawczak, M., Schreiber, S., Nikolaus, S., et al. (2010) · Molecular Psychiatry · doi:10.1038/mp.2008.141 · Cited by 128
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Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer's disease
Lunnon, K., Smith, R., Hannon, E., De Jager, P. L., Srivastava, G., Volta, M., Troakes, C., Al-Sarraj, S., Burrage, J., Macdonald, R., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3782 · Cited by 574
25-Hydroxycholesterol amplifies microglial IL-1β production in an apoE isoform-dependent manner
Wong, M. Y., Lewis, M., Doherty, J. J., Shi, Y., Cashikar, A. G., Amelianchik, A., Tymchuk, S., Sullivan, P. M., Qian, M., Covey, D. F., et al. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01869-3 · Cited by 121
Beck, T. N., Nicolas, E., Kopp, M. C., & Golemis, E. A. (2014) · Oncoscience · doi:10.18632/oncoscience.64 · Cited by 50
DAPK1: a Novel Pathology and Treatment Target for Alzheimer’s Disease
Xu, L.-Z., Li, B.-Q., & Jia, J.-P. (2019) · Molecular Neurobiology · doi:10.1007/s12035-018-1242-2 · Cited by 42
Metadata
- Authors
- Laumet, G., Chouraki, V., Grenier-Boley, B., Legry, V., Heath, S., Zelenika, D., Fievet, N., Hannequin, D., Delepine, M., Pasquier, F., Hanon, O., Brice, A., Epelbaum, J., Berr, C., Dartigues, J.-F., Tzourio, C., Campion, D., Lathrop, M., Bertram, L., Amouyel, P., & Lambert, J.-C.
- Affiliations
- INSERM U744, Lille, France
- Centre National de Génotypage, Institut Génomique, Commissariat à l'Energie Atomique, Evry, France
- INSERM U614, Faculté de Médecine-Pharmacie de Rouen, Rouen, France
- Université de Lille Nord de France, Lille, France
- UMR 894, Inserm Faculté de Médecine, Université Paris Descartes, Paris, France
- Inserm, UMR_S679, Hôpital de la Salpêtrière, Paris, France
- INSERM U888, Hôpital La Colombière, Montpellier, France
- INSERM U897, Victor Segalen University, Bordeaux, France
- INSERM U708, Paris, France
- Neuropsychiatric Genetics Group, Department of Vertebrate Genomics, Max-Planck Institute for Molecular Genetics, Berlin, Germany
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2010-06-13
- Volume
- 20
- Issue
- 4
- Pages
- 1181-1188
- ISSN
- 1875-8908
- 1387-2877
- Cited by
- 58
- References
- 6
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