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

A. R. Morgan, G. Hamilton, D. Turic, L. Jehu, D. Harold, R. Abraham, P. Hollingworth, V. Moskvina, C. Brayne, D. C. Rubinsztein, A. Lynch, B. Lawlor, M. Gill, M. O'Donovan, J. Powell, S. Lovestone, J. Williams, M. J. Owen

Research output: Contribution to journalArticle

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.
Original languageEnglish
Pages (from-to)727-731
Number of pages5
JournalAmerican journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
Volume147b
Issue number6
DOIs
Publication statusPublished - 5 Sep 2008

Keywords

  • late-onset Alzheimer's disease
  • chromosome 10
  • SNP
  • association

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    Morgan, A. R., Hamilton, G., Turic, D., Jehu, L., Harold, D., Abraham, R., Hollingworth, P., Moskvina, V., Brayne, C., Rubinsztein, D. C., Lynch, A., Lawlor, B., Gill, M., O'Donovan, M., Powell, J., Lovestone, S., Williams, J., & Owen, M. J. (2008). 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 : the official publication of the International Society of Psychiatric Genetics, 147b(6), 727-731. https://doi.org/10.1002/ajmg.b.30670