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A survey of ABCA1 sequence variation confirms association with dementia.

TitleA survey of ABCA1 sequence variation confirms association with dementia.
Publication TypeJournal Article
Year of Publication2009
AuthorsReynolds, CA, Hong, M-G, Eriksson, UK, Blennow, K, Bennet, AM, Johansson, B, Malmberg, B, Berg, S, Wiklund, F, Gatz, M, Pedersen, NL, Prince, JA
JournalHum Mutat
Date Published2009 Sep
KeywordsAged, Aged, 80 and over, ATP Binding Cassette Transporter 1, ATP-Binding Cassette Transporters, Base Sequence, Case-Control Studies, Data Collection, Dementia, Female, Genetic Variation, Genome-Wide Association Study, Genotype, Haplotypes, Humans, Male

We and others have conducted targeted genetic association analyses of ABCA1 in relation to Alzheimer disease risk with a resultant mixture of both support and refutation, but all previous studies have been based upon only a few markers. Here, a detailed survey of genetic variation in the ABCA1 region has been performed in a total of 1,567 Swedish dementia cases (including 1,275 with Alzheimer disease) and 2,203 controls, providing evidence of association with maximum significance at marker rs2230805 (odds ratio [OR]=1.39; 95% confidence interval [CI] 1.23-1.57, p=7.7x10(-8)). Haplotype-based tests confirmed association of this genomic region after excluding rs2230805, and imputation did not reveal additional markers with greater support. Significantly associating markers reside in two distinct linkage disequilibrium blocks with maxima near the promoter and in the terminal exon of a truncated ABCA1 splice form. The putative risk allele of rs2230805 was also found to be associated with reduced cerebrospinal fluid levels of beta-amyloid. The strongest evidence of association was obtained when all forms of dementia were considered together, but effect sizes were similar when only confirmed Alzheimer disease cases were assessed. Results further implicate ABCA1 in dementia, reinforcing the putative involvement of lipid transport in neurodegenerative disease.

Alternate JournalHum. Mutat.
PubMed ID19606474
PubMed Central IDPMC2758418
Grant ListAG028555 / AG / NIA NIH HHS / United States
R01 AG008724 / AG / NIA NIH HHS / United States
R01 AG028555-03 / AG / NIA NIH HHS / United States
R01 AG028555 / AG / NIA NIH HHS / United States
AG08861 / AG / NIA NIH HHS / United States
AG08724 / AG / NIA NIH HHS / United States