Sequence variation in SORL1 and dementia risk in Swedes.
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.
Reynolds
Chandra A
CA
Department of Psychology, University of California at Riverside, Riverside, CA 92521, USA.
Hong
Mun-Gwan
MG
Eriksson
Ulrika K
UK
Blennow
Kaj
K
Johansson
Boo
B
Malmberg
Bo
B
Berg
Stig
S
Gatz
Margaret
M
Pedersen
Nancy L
NL
Bennet
Anna M
AM
Prince
Jonathan A
JA
D000544:Alzheimer Disease / Q000208:ethnology / Q000235:genetics; D003704:Dementia / Q000235:genetics*; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D015810:Linkage Disequilibrium; D026901:Membrane Transport Proteins / Q000235:genetics*; D008957:Models, Genetic; D040641:Quantitative Trait Loci; D012306:Risk; D013548:Sweden
D005819:Genetic Markers; D026502:LDL-Receptor Related Proteins; D026901:Membrane Transport Proteins; C102582:SORL1 protein, human