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. 2011:2011:505984.
doi: 10.4061/2011/505984. Epub 2011 Jun 12.

Alzheimer's disease genes are associated with measures of cognitive ageing in the lothian birth cohorts of 1921 and 1936

Gillian Hamilton  1 , Sarah E Harris, Gail Davies, David C Liewald, Albert Tenesa, John M Starr, David Porteous, Ian J Deary
Affiliations

Alzheimer's disease genes are associated with measures of cognitive ageing in the lothian birth cohorts of 1921 and 1936

Gillian Hamilton et al. Int J Alzheimers Dis. 2011.

Abstract

Alzheimer's disease patients have deficits in specific cognitive domains, and susceptibility genes for this disease may influence human cognition in nondemented individuals. To evaluate the role of Alzheimer's disease-linked genetic variation on cognition and normal cognitive ageing, we investigated two Scottish cohorts for which assessments in major cognitive domains are available: the Lothian Birth Cohort of 1921 and the Lothian Birth Cohort of 1936, consisting of 505 and 998 individuals, respectively. 158 SNPs from eleven genes were evaluated. Single SNP analyses did not reveal any statistical association after correction for multiple testing. One haplotype from TRAPPC6A was associated with nonverbal reasoning in both cohorts and combined data sets. This haplotype explains a small proportion of the phenotypic variability (1.8%). These findings warrant further investigation as biological modifiers of cognitive ageing.

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Figures

Figure 1
Figure 1
Genomic structure of positively associated genes. (a) Genomic structure of APP, BIN1, and chromosome 19. Highlighted are the location of each SNP genotyped and the location of positively associated haplotypes and gene-gene interactions. (b) LD structure of APP, BIN1, and chromosome 19 in the Lothian Birth Cohorts of 1936 (top) and 1921 (bottom). LD values used were D′.
Figure 2
Figure 2
The interaction of an SNP pair from BIN1 and APP is likely to influence logical memory in the APOE ε4 positive subset of LBC1936. Analysis of both the (a) genotype cognitive means and (b) the allele specific means shows that the initial positive result is due to two individuals carrying both minor alleles, aabb. Genotype legend; 11 = AaBb, 10 = AaBB, 01 = AABb, 00 = AABB, 12 = Aabb, 01 = AAbb, 21 = aaBb, 20 = aaBB, 22 = aabb. Allele legend; 1 = aabb, 2 = aaB-, 3 = A-bb, 4 = A-B-.
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