| 1. |
- Reynolds, Chandra A, et al.
(författare)
-
A survey of ABCA1 sequence variation confirms association with dementia.
- 2009
-
Ingår i: Human mutation. - : Hindawi Limited. - 1098-1004 .- 1059-7794. ; 30:9, s. 1348-54
-
Tidskriftsartikel (refereegranskat)abstract
- We and others have conducted targeted genetic association analyses of ABCA1 in relation to Alzheimer disease risk with a resultant mixture of both support and refutation, but all previous studies have been based upon only a few markers. Here, a detailed survey of genetic variation in the ABCA1 region has been performed in a total of 1,567 Swedish dementia cases (including 1,275 with Alzheimer disease) and 2,203 controls, providing evidence of association with maximum significance at marker rs2230805 (odds ratio [OR]=1.39; 95% confidence interval [CI] 1.23-1.57, p=7.7x10(-8)). Haplotype-based tests confirmed association of this genomic region after excluding rs2230805, and imputation did not reveal additional markers with greater support. Significantly associating markers reside in two distinct linkage disequilibrium blocks with maxima near the promoter and in the terminal exon of a truncated ABCA1 splice form. The putative risk allele of rs2230805 was also found to be associated with reduced cerebrospinal fluid levels of beta-amyloid. The strongest evidence of association was obtained when all forms of dementia were considered together, but effect sizes were similar when only confirmed Alzheimer disease cases were assessed. Results further implicate ABCA1 in dementia, reinforcing the putative involvement of lipid transport in neurodegenerative disease.
|
|
| 2. |
- Reynolds, Chandra A, et al.
(författare)
-
Sequence variation in SORL1 and dementia risk in Swedes.
- 2010
-
Ingår i: Neurogenetics. - : Springer Science and Business Media LLC. - 1364-6753 .- 1364-6745. ; 11:1, s. 139-42
-
Tidskriftsartikel (refereegranskat)abstract
- The gene encoding the neuronal sortilin-related receptor SORL1 has been claimed to be associated with Alzheimer's disease (AD) by independent groups and across various human populations. We evaluated six genetic markers in SORL1 in a sample of 1,558 Swedish dementia cases (including 1,270 AD cases) and 2,179 controls. For both single-marker-based and haplotype-based analyses, we found no strong support for SORL1 as a dementia or AD risk-modifying gene in our sample in isolation nor did we observe association with AD/dementia-related traits, including cerebrospinal fluid beta-amyloid(1-42), tau levels, or age at onset. However, meta-analyses of markers in this study together with previously published studies on SORL1 encompassing in excess of 13,000 individuals does suggest significant association with AD (best odds ratio = 1.097; 95% confidence interval = 1.038-1.158, p = 0.001). All six markers were significant in meta-analyses and it is notable that they occur in two distinct linkage disequilibrium blocks. These data are consistent with either allelic heterogeneity or the existence of as yet untested functional variants and these will be important considerations in further attempts to evaluate the importance of sequence variation in SORL1 with AD risk.
|
|
