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Sequence variation in SORL1 and dementia risk in Swedes.

Reynolds, Chandra A (author)
Hong, Mun-Gwan (author)
Karolinska Institutet
Eriksson, Ulrika K (author)
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Blennow, Kaj, 1958 (author)
Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Johansson, Boo (author)
Gothenburg University,Göteborgs universitet,Psykologiska institutionen,Department of Psychology
Malmberg, Bo, 1946- (author)
Jönköping University,HHJ, Institutet för gerontologi,HHJ. Åldrande - livsvillkor och hälsa
Berg, Stig, 1947- (author)
Jönköping University,HHJ, Institutet för gerontologi,HHJ. Åldrande - livsvillkor och hälsa
Gatz, Margaret (author)
Pedersen, Nancy L (author)
Karolinska Institutet
Bennet, Anna M (author)
Karolinska Institutet
Prince, Jonathan A (author)
Karolinska Institutet
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 (creator_code:org_t)
2009-08-04
2010
English.
In: Neurogenetics. - : Springer Science and Business Media LLC. - 1364-6753 .- 1364-6745. ; 11:1, s. 139-42
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Psykiatri (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Psychiatry (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Geriatrik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Geriatrics (hsv//eng)

Keyword

Alzheimer Disease
ethnology
genetics
Dementia
genetics
Genetic Markers
Genetic Predisposition to Disease
Genetic Variation
Haplotypes
Humans
LDL-Receptor Related Proteins
genetics
Linkage Disequilibrium
Membrane Transport Proteins
genetics
Models
Genetic
Quantitative Trait Loci
Risk
Sweden
Geriatrics and medical gerontology

Publication and Content Type

ref (subject category)
art (subject category)

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