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

doi: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

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

Biological and Biomedical Sciences

Research output: Contribution to journal › Article

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 language	English
Pages (from-to)	727-731
Number of pages	5
Journal	American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
Volume	147b
Issue number	6
DOIs	https://doi.org/10.1002/ajmg.b.30670
Publication status	Published - 5 Sep 2008

Keywords

late-onset Alzheimer's disease
chromosome 10
SNP
association

Documents and Links

10.1002/ajmg.b.30670

Fingerprint Dive into the research topics of 'Association analysis of 528 intra-genic SNPs in a region of chromosome 10 linked to late onset Alzheimer's disease'. Together they form a unique fingerprint.

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. (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

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.

@article{e619bc82cc46413e9b7482ed342665d8,

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

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.",

keywords = "late-onset Alzheimer's disease, chromosome 10, SNP, association",

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

year = "2008",

month = sep,

day = "5",

doi = "10.1002/ajmg.b.30670",

language = "English",

volume = "147b",

pages = "727--731",

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

issn = "1552-4841",

number = "6",

}

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 journal › Article

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

IS - 6

ER -

Morgan AR, Hamilton G, Turic D, Jehu L, Harold D, Abraham R et al. 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. 2008 Sep 5;147b(6):727-731. https://doi.org/10.1002/ajmg.b.30670