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P3‐276: BRI2 (ITM2B) shows genetic association with late‐onset Alzheimer's disease
Author(s) -
Zou Fanggeng,
Kim Jungsu,
Miller Victor M.,
Levites Yona,
Ma Li,
Cangemi David,
Bisceglio Gina,
Younkin Samuel,
Pankratz Ver S.,
Petersen Ronald C.,
Graff-Radford Neil,
Dickson Dennis,
Rosenberry Terrone,
Golde Todd,
Younkin Steven G.
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.1844
Subject(s) - haplotype , single nucleotide polymorphism , neurodegeneration , genotype , biology , genetic association , alzheimer's disease , disease , gene , medicine , genetically modified mouse , genetics , endocrinology , transgene
both with and without adjustment for genomic control (GC) as well as empirical p values. We also compared our LOAD GWAS results with the Braak GWAS results. Results: After stringent quality control based on Hardy-Weinberg disequilibrium, missing genotypes and minor allele frequencies, high quality genotypes were obtained for 306,672 SNPs. We analyzed the AD cases and controls separately to avoid stratification bias. None of the SNPs had genome-wide significance after Bonferroni correction. In the AD cases, there were 79 SNPs with GC adjusted p 0.0002. In the controls, there were 81 such SNPs. These represent an excess of 17-27 SNPs under the null hypothesis of no association. The unadjusted, GC adjusted and empirical p values were highly correlated. There were SNPs with evidence of Braak NFT stage association in both the cases and controls. There were SNPs with evidence of association with both AD and Braak stage. Linear regression analysis of Braak NFT stage in the ADs, after including age, sex and ApoE as covariates, led to the identification of 78 SNPs with p 0.0002. Conclusions: These results suggest the presence of variants in the human genome that may be associated with both risk of AD and brain NFT pathology. Given that the Braak GWAS is performed in only a subset of our total series, constituting 12-16% of the subjects from our LOAD GWAS, use of Braak stage endophenotype deserves further exploration as a methodology to detect susceptibility variants for late onset Alzheimer’s disease. (*) Equal contribution.