Sequence variation in SORL1 and dementia risk in Swedes (original) (raw)

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.

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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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Authors and Affiliations

  1. Department of Psychology, University of California at Riverside, Riverside, CA, 92521, USA
    Chandra A. Reynolds
  2. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12A, 171 77, Stockholm, Sweden
    Mun-Gwan Hong, Ulrika K. Eriksson, Margaret Gatz, Nancy L. Pedersen, Anna M. Bennet & Jonathan A. Prince
  3. Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, 431 80, Mölndal, Sweden
    Kaj Blennow
  4. Department of Psychology, University of Gothenburg, 405 30, Gothenburg, Sweden
    Boo Johansson
  5. Institute of Gerontology, School of Health Sciences, Jönköping University, 551 11, Jönköping, Sweden
    Bo Malmberg & Stig Berg
  6. Department of Psychology, University of Southern California, Los Angeles, CA, 90089-1061, USA
    Margaret Gatz & Nancy L. Pedersen

Authors

  1. Chandra A. Reynolds
  2. Mun-Gwan Hong
  3. Ulrika K. Eriksson
  4. Kaj Blennow
  5. Boo Johansson
  6. Bo Malmberg
  7. Stig Berg
  8. Margaret Gatz
  9. Nancy L. Pedersen
  10. Anna M. Bennet
  11. Jonathan A. Prince

Corresponding author

Correspondence toJonathan A. Prince.

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Reynolds, C.A., Hong, MG., Eriksson, U.K. et al. Sequence variation in SORL1 and dementia risk in Swedes.Neurogenetics 11, 139–142 (2010). https://doi.org/10.1007/s10048-009-0210-4

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