Mutations in ABCA7 in a Belgian cohort of Alzheimer's disease patients: a targeted resequencing study

Cuyvers, Elise; Roeck, Arne De; Bossche, Tobi Van den; Cauwenberghe, Caroline Van; Bettens, Karolien; Vermeulen, Steven; Mattheijssens, Maria; Peeters, Karin; Engelborghs, Sebastiaan; Vandenbulcke, Mathieu; Vandenberghe, Rik; Deyn, Peter Paul De; Broeckhoven, Christine Van; Sleegers, Kristel

doi:10.1016/s1474-4422(15)00133-7

Cited by 135 publications

(168 citation statements)

References 31 publications

Supporting

Mentioning

149

Contrasting

Order By: Relevance

“…Common variation in ABCA7 was first reported to be associated with risk of Alzheimer's disease in a large genome‐wide association study 6. Subsequently rare loss‐of‐function mutations in ABCA7 were shown to be associated with Alzheimer's disease in Icelandic and Belgian populations 15, 16. Since Iceland has a modest, relatively isolated population, genetic variants are more likely to be passed down through generations than in larger mixed populations 40.…”

Section: Discussionmentioning

confidence: 99%

“…Since Iceland has a modest, relatively isolated population, genetic variants are more likely to be passed down through generations than in larger mixed populations 40. Furthermore, analyses of rare mutations can be sensitive to bias because of population stratification and hidden relatedness 16. Therefore, such findings may not be applicable to other populations.…”

Section: Discussionmentioning

confidence: 99%

“…The studies on loss‐of‐function mutations in ABCA7 suggest that loss of ABCA7 could be a potential pathogenic mechanism underlying Alzheimer's disease,15, 16 but also functional studies of a common missense variant in exon 33 (rs3752246, p.Gly1527Ala) support this 41. Rs3752246 was identified in a North American study,42 and is in high LD with the present rs4147929 variant (http://snipa.helmholtz-muenchen.de/snipa3/, r 2 =0.97).…”

Section: Discussionmentioning

confidence: 99%

“…Genome‐wide association studies (GWAS) have revealed novel molecular pathways, among these the ATP‐binding‐cassette transporter A7 ( ABCA7 ),5, 6 which may be involved in both transmembrane lipid transport and phagocytosis of amyloid‐ β in the brain 7, 8, 9, 10, 11, 12, 13, 14. Following these GWAS findings, rare loss‐of‐function variants in ABCA7 were reported to confer risk of Alzheimer's disease in case–control studies in Icelandic and Belgian populations 15, 16. Whether common genetic variation in ABCA7 confers risk of dementia, ischemic heart‐ and cerebrovascular disease in the general population, and whether potential associations are independent of the strong Alzheimer's disease apolipoprotein E ( APOE ) ɛ 4 risk allele remains to be determined.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

ABCA7 and risk of dementia and vascular disease in the Danish population

Kjeldsen

Tybjærg‐Hansen

Nordestgaard

et al. 2017

Ann Clin Transl Neurol

View full text Add to dashboard Cite

Objective ATP‐binding‐cassette transporter A7(ABCA7) is suggested to be involved in lipid transport as well as in phagocytosis of amyloid‐β in the brain. We tested the hypothesis that a common genetic variant in ABCA7 is associated with dementia, ischemic heart disease, ischemic cerebrovascular disease, and with lipid levels in the general population, independent of the common apolipoprotein E(APOE) genotype.MethodsFor this purpose, we genotyped a common genetic variant in ABCA7, identified in genome‐wide‐association‐studies of Alzheimer's disease, in 104,258 individuals from the Danish general population, and also meta‐analyzed our results with publicly available consortia data.ResultsMultifactorially adjusted hazard ratios for Alzheimer's disease were 1.07 (95% confidence interval:0.93–1.23) and 1.72 (1.24–2.40) for GA and AA versus GG genotype. Results were similar after APOE genotype adjustment and when only APOE ɛ33 carriers were studied. Including 178,304 individuals, the meta‐analyzed odds ratio for Alzheimer's disease per one allele ABCA7 rs4147929 increase was 1.15 (1.12–1.18). ABCA7 genotype was not convincingly associated with vascular dementia, ischemic heart disease, ischemic cerebrovascular disease, or with lipid levels. Including 288,563 individuals, meta‐analyzed odds ratios for ischemic heart disease per one allele ABCA7 rs4147929 increase was 1.01 (0.99–1.03).InterpretationA common genetic variant in ABCA7 was associated with high risk of Alzheimer's disease independent of APOE genotype. The lack of association with vascular dementia, ischemic heart disease, ischemic cerebrovascular disease, and with lipid levels suggests that ABCA7 is not important for atherosclerosis. Thus, our findings support the suggested role of ABCA7 in Alzheimer's disease pathology and phagocytic clearance of amyloid‐β in the brain.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

ABCA7 and risk of dementia and vascular disease in the Danish population

Kjeldsen

Tybjærg‐Hansen

Nordestgaard

et al. 2017

Ann Clin Transl Neurol

View full text Add to dashboard Cite

show abstract

“…Examples include CLU [4], CLU, PICALM and CR1 [5], ABCA7 [6] and ABCA7, BIN1, CD2AP, CLU, CR1, EPHA1, MS4A4/MS4A6A [7]. All studies, apart from [5], have used targeted exome sequencing, ignoring variants which may be found in the noncoding and intronic regions of the loci.…”

Section: Introductionmentioning

confidence: 99%

Investigating Splicing Variants Uncovered by Next-Generation Sequencing the Alzheimer’s Disease Candidate Genes, CLU, PICALM, CR1, ABCA7, BIN1, the MS4A Locus, CD2AP, EPHA1 and CD33

Clement¹,

Braae²,

Turton³

et al. 2016

J Alzheimers Dis Parkinsonism

View full text Add to dashboard Cite

Association of rare variants in neurodegenerative genes with familial Alzheimer’s disease

Zhang

Jiao

Xiao

et al. 2020

Ann Clin Transl Neurol

View full text Add to dashboard Cite

Objective: To investigate the impact of rare variants underlying neurodegenerative-related genes to familial Alzheimer's disease (AD). Methods: We performed targeted sequencing of 277 neurodegenerative-related genes on probands from 75 Chinese AD families non-carrying causative mutation of dementia genes. Rare coding variants segregated in families were tested for association in an independent cohort of 506 patients with sporadic AD and 498 cognitively normal controls. East Asians data from the Exome Aggregation Consortium (ExAC) were used as a reference control. Results: A novel rare variant, P410S of PLD3 was found in an early-onset AD family. LRRK2 I2012T, a causative mutation of Parkinson's disease, was identified in another early-onset AD family. Missense variants in ABCA7 (P143S and A1507T) and CR1 (T239M) were significantly associated with familial AD (P = 0.005437, 0.001383, 0.000549), a missense variant in TREM2(S183C) was significantly associated with AD (P = 0.000396) when compared with the East Asian controls in ExAC database. A non-frameshift variant in FUS (G223del) was frequent in AD cases and significantly associated with familial AD (P = 0.008). Interpretation: Multiple rare coding variants of causal and risk neurodegenerative genes were presented in clinically diagnosed AD families that may confer risk of AD. Our data supported that the clinical, pathological, and genetic architectures of AD, PD, and FTD/ALS may overlapping. We propose that targeted sequencing on neurodegenerative-related genes is necessary for genetically unclear AD families.

show abstract

Mutations in ABCA7 in a Belgian cohort of Alzheimer's disease patients: a targeted resequencing study

Cited by 135 publications

References 31 publications

ABCA7 and risk of dementia and vascular disease in the Danish population

ABCA7 and risk of dementia and vascular disease in the Danish population

Investigating Splicing Variants Uncovered by Next-Generation Sequencing the Alzheimer’s Disease Candidate Genes, CLU, PICALM, CR1, ABCA7, BIN1, the MS4A Locus, CD2AP, EPHA1 and CD33

Association of rare variants in neurodegenerative genes with familial Alzheimer’s disease

Contact Info

Product

Resources

About