Sequence variation in SORL1 and dementia risk in Swedes |
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Authors: | 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 |
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Affiliation: | 1. Department of Psychology, University of California at Riverside, Riverside, CA, 92521, USA 2. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels v?g 12A, 171 77, Stockholm, Sweden 3. Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, 431 80, M?lndal, Sweden 4. Department of Psychology, University of Gothenburg, 405 30, Gothenburg, Sweden 5. Institute of Gerontology, School of Health Sciences, J?nk?ping University, 551 11, J?nk?ping, Sweden 6. Department of Psychology, University of Southern California, Los Angeles, CA, 90089-1061, USA
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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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