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Meta-Analysis
. 2010 Feb;11(1):139-42.
doi: 10.1007/s10048-009-0210-4. Epub 2009 Aug 4.

Sequence variation in SORL1 and dementia risk in Swedes

Chandra A Reynolds  1 , Mun-Gwan Hong, Ulrika K Eriksson, Kaj Blennow, Boo Johansson, Bo Malmberg, Stig Berg, Margaret Gatz, Nancy L Pedersen, Anna M Bennet, Jonathan A Prince
Affiliations
Meta-Analysis

Sequence variation in SORL1 and dementia risk in Swedes

Chandra A Reynolds et al. Neurogenetics. 2010 Feb.

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.

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Figures

Fig. 1
Fig. 1
Meta-analyses of SORL1 genotypes in relation to risk of AD showing a) A literature-based based meta-analysis of individual studies of SNP rs2282649 and b) The combined estimates resulting from individual meta-analyses of six different SNPs, including rs2282649. Studies listed in the meta-analysis for rs22382649 can be found summarized at http://www.alzforum.org/res/com/gen/alzgene/. Results are from fixed effects models. Tests for heterogeneity for each genotype: rs2282649; Q=13.82, p= 0.312, rs3824968; Q=25.60, p=0.013, rs2070045; Q= 18.33, p= 0.05, rs641120; Q=5.88, p= 0.66, rs689021; Q= 14.85, p=0.19, rs668387; Q= 17.21, p=0.19
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