Association analysis of 528 intra-genic SNPs in a region of chromosome 10 linked to late onset Alzheimer's disease

Morgan, A.R., Hamilton, G., Turic, Dragana, Jehu, L., Harold, Denise ORCID: https://orcid.org/0000-0001-5195-0143, Abraham, Richard Alun, Hollingworth, Paul, Escott-Price, Valentina ORCID: https://orcid.org/0000-0003-1784-5483, Brayne, C., Rubinsztein, D.C., Lynch, A., Lawlor, B., Gill, M., O'Donovan, Michael Conlon ORCID: https://orcid.org/0000-0001-7073-2379, Powell, J., Lovestone, S., Williams, Julie ORCID: https://orcid.org/0000-0002-4069-0259 and Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862 2007. Association analysis of 528 intra-genic SNPs in a region of chromosome 10 linked to late onset Alzheimer's disease. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 147B (6) , pp. 727-731. 10.1002/ajmg.b.30670

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Abstract

Late-onset Alzheimer's disease (LOAD) is a genetically complex neurodegenerative disorder. Currently, only the epsilon4 allele of the Apolipoprotein E gene has been identified unequivocally as a genetic susceptibility factor for LOAD. Others remain to be found. In 2002 we observed genome-wide significant evidence of linkage to a region on chromosome 10q11.23-q21.3 [Myers et al. (2002) Am J Med Genet 114:235-244]. Our objective in this study was to test every gene within the maximum LOD-1 linkage region, for association with LOAD. We obtained results for 528 SNPs from 67 genes, with an average density of 1 SNP every 10 kb within the genes. We demonstrated nominally significant association with LOAD for 4 SNPs: rs1881747 near DKK1 (P = 0.011, OR = 1.24), rs2279420 in ANK3 (P = 0.022, OR = 0.79), rs2306402 in CTNNA3 (P = 0.024, OR = 1.18), and rs5030882 in CXXC6 (P = 0.046, OR = 1.29) in 1,160 cases and 1,389 controls. These results would not survive correction for multiple testing but warrant attempts at confirmation in independent samples.

Item Type:	Article
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI) MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > R Medicine (General)
Uncontrolled Keywords:	late-onset Alzheimer's disease; chromosome 10; SNP; association
Publisher:	International Society of Psychiatric Genetics
ISSN:	1552-4841
Last Modified:	19 Oct 2022 09:43
URI:	https://orca.cardiff.ac.uk/id/eprint/21989

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