Genetic variants conferring susceptibility to Alzheimer’s disease in the general population; do they also predispose to dementia in Down’s syndrome

Patel, Ashok, Rees, Simon D, Kelly, M, Bain, Stephen C, Barnett, Anthony H, Prasher, Anisha, Arshad, Humaria and Prasher, Vee P (2014) Genetic variants conferring susceptibility to Alzheimer’s disease in the general population; do they also predispose to dementia in Down’s syndrome. BMC Research Notes, 7 (1). p. 42. ISSN 1756-0500. Full Text available at

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Background: Down’s syndrome (DS) is caused by either complete or partial triplication of chromosome 21,
17 affecting approximately 1/1000 live births, and it is widely accepted that individuals with DS are more likely to
18 develop dementia of Alzheimer’s disease (DAD) compared with the general population. Recent collaborative
19 genome-wide association studies of large case control data sets of individuals with and without Alzhemier’s disease
20 (AD) have revealed new risk variants for dementia, as well as confirming previously identified risk variants. In this
21 study, nine AD-derived SNPs, near or within the CR1 (rs3818361), BIN1 (rs744373), CD2AP (rs9349407), EPHA1
22 (rs11767557), CLU (rs1532278), MS4A6A/4A (rs610932), PICALM (rs561655), ABCA7 (rs3764650) and CD33 (rs3865444)
23 genes were genotyped in 295 individuals with DS.
24 Results: There were no significant associations between these nine GWAS-derived SNPs and DAD in British
25 Caucasian individuals with DS. Interestingly the CR1 rs3818361 variant appeared to be associated with mortality in
26 our cohort, particularly in the subjects without dementia. To our knowledge, this is the first time that this variant
27 has been implicated as a determinant of mortality and the finding warrants further investigation in other cohorts
28 with DS.
29 Conclusions: This study shows negative associations of nine AD-derived SNPs with DAD in DS. This may be due to
30 the modest size of our cohort, which may indicate that our study is insufficiently powered to pick up such
31 associations. We cannot conclusively exclude a role for these SNPs in DAD in DS. Clearly, efforts to investigate
32 genetic variants with small effects on disease risk require a much larger cohort of individuals with DS. In fact, we
33 hypothesize that a sample size of 4465 individuals with DS would be needed to determine the role in DAD in DS
34 of the nine AD-derived SNPs investigated in this study. We therefore recommend that all national and international
35 clinics with access to individuals with DS should contribute DNA samples to form DS consortia.

Item Type: Article
Additional Information: Full Text available at
Subjects: WM Psychiatry. Mental health
WT Geriatrics. Elderly care
Divisions: Ambulatory Care > Diabetes
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Depositing User: Users 7 not found.
Date Deposited: 24 Jun 2014 08:19
Last Modified: 24 Jun 2014 08:19

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