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neurogenetics

, Volume 11, Issue 1, pp 139–142 | Cite as

Sequence variation in SORL1 and dementia risk in Swedes

  • Chandra A. Reynolds
  • 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
SHORT COMMUNICATION

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 β-amyloid1–42, 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.

Keywords

SORL1 Alzheimer Meta-analysis Association Swedish 

Notes

Acknowledgements

We are grateful for the generous funding from the US National Institutes of Health (grants AG028555, AG08724, and AG08861) and the Swedish Medical Research Council (grant 2007-2722).

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Chandra A. Reynolds
    • 1
  • Mun-Gwan Hong
    • 2
  • Ulrika K. Eriksson
    • 2
  • Kaj Blennow
    • 3
  • Boo Johansson
    • 4
  • Bo Malmberg
    • 5
  • Stig Berg
    • 5
  • Margaret Gatz
    • 2
    • 6
  • Nancy L. Pedersen
    • 2
    • 6
  • Anna M. Bennet
    • 2
  • Jonathan A. Prince
    • 2
  1. 1.Department of PsychologyUniversity of California at RiversideRiversideUSA
  2. 2.Department of Medical Epidemiology and BiostatisticsKarolinska InstitutetStockholmSweden
  3. 3.Institute of Neuroscience and PhysiologySahlgrenska Academy at University of GothenburgMölndalSweden
  4. 4.Department of PsychologyUniversity of GothenburgGothenburgSweden
  5. 5.Institute of Gerontology, School of Health SciencesJönköping UniversityJönköpingSweden
  6. 6.Department of PsychologyUniversity of Southern CaliforniaLos AngelesUSA

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