A survey of ABCA1 sequence variation confirms association with dementia.

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.

Hong, Mun-GwanKarolinska Institutet (author)
Eriksson, Ulrika KKarolinska Institutet (author)
Blennow, Kaj,1958Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xbleka (author)
Bennet, Anna MKarolinska Institutet (author)
Johansson, BooGothenburg University,Göteborgs universitet,Psykologiska institutionen,Department of Psychology(Swepub:gu)xjoboo (author)
Malmberg, Bo,1946-Jönköping University,HHJ, Institutet för gerontologi,HHJ. Åldrande - livsvillkor och hälsa(Swepub:hj)malb (author)
Berg, Stig,1947-Jönköping University,HHJ, Institutet för gerontologi,HHJ. Åldrande - livsvillkor och hälsa(Swepub:hj)best (author)
Wiklund, FredrikKarolinska Institutet (author)
Gatz, Margaret (author)
Pedersen, Nancy LKarolinska Institutet (author)
Prince, Jonathan AKarolinska Institutet (author)
Karolinska InstitutetInstitutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi (creator_code:org_t)

By the author/editor: Reynolds, Chandr ...; Hong, Mun-Gwan; Eriksson, Ulrika ...; Blennow, Kaj, 19 ...; Bennet, Anna M; Johansson, Boo; show more...; Malmberg, Bo, 19 ...; Berg, Stig, 1947 ...; Wiklund, Fredrik; Gatz, Margaret; Pedersen, Nancy ...; Prince, Jonathan ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Psychiatry

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Geriatrics

By the university: University of Gothenburg; Karolinska Institutet; Jönköping University

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.