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

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Chromosomes, Human, Pair 10
Single Nucleotide Polymorphism
Alzheimer Disease
Genes
Viverridae
Apolipoproteins E
Genetic Predisposition to Disease
Neurodegenerative Diseases
Chromosomes
Alleles
Genome

Keywords

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

Cite this

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. / Association analysis of 528 intra-genic SNPs in a region of chromosome 10 linked to late onset Alzheimer's disease. In: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. 2008 ; Vol. 147b, No. 6. pp. 727-731.
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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.",
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Morgan, AR, Hamilton, G, Turic, D, Jehu, L, Harold, D, Abraham, R, Hollingworth, P, Moskvina, V, Brayne, C, Rubinsztein, DC, Lynch, A, Lawlor, B, Gill, M, O'Donovan, M, Powell, J, Lovestone, S, Williams, J & Owen, MJ 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, vol. 147b, no. 6, pp. 727-731. https://doi.org/10.1002/ajmg.b.30670

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, 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.

In: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, Vol. 147b, No. 6, 05.09.2008, p. 727-731.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association analysis of 528 intra-genic SNPs in a region of chromosome 10 linked to late onset Alzheimer's disease

AU - Morgan, A. R.

AU - Hamilton, G.

AU - Turic, D.

AU - Jehu, L.

AU - Harold, D.

AU - Abraham, R.

AU - Hollingworth, P.

AU - Moskvina, V.

AU - Brayne, C.

AU - Rubinsztein, D. C.

AU - Lynch, A.

AU - Lawlor, B.

AU - Gill, M.

AU - O'Donovan, M.

AU - Powell, J.

AU - Lovestone, S.

AU - Williams, J.

AU - Owen, M. J.

PY - 2008/9/5

Y1 - 2008/9/5

N2 - 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.

AB - 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.

KW - late-onset Alzheimer's disease

KW - chromosome 10

KW - SNP

KW - association

U2 - 10.1002/ajmg.b.30670

DO - 10.1002/ajmg.b.30670

M3 - Article

VL - 147b

SP - 727

EP - 731

JO - American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics

JF - American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics

SN - 1552-4841

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