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 -