Opin vísindi

Association of common genetic variants with brain microbleeds : A genome-wide association study

Show simple item record

dc.contributor.author Alzheimer's Disease Neuroimaging Initiative
dc.date.accessioned 2022-07-09T01:02:53Z
dc.date.available 2022-07-09T01:02:53Z
dc.date.issued 2020-12-15
dc.identifier.citation Alzheimer's Disease Neuroimaging Initiative 2020 , ' Association of common genetic variants with brain microbleeds : A genome-wide association study ' , Neurology , vol. 95 , no. 24 , pp. e3331-e3343 . https://doi.org/10.1212/WNL.0000000000010852
dc.identifier.issn 0028-3878
dc.identifier.other PURE: 38447279
dc.identifier.other PURE UUID: 0d150d62-ca2f-4028-91aa-ba5d2b84da96
dc.identifier.other Scopus: 85098521230
dc.identifier.uri https://hdl.handle.net/20.500.11815/3286
dc.description This study was not industry sponsored. M.J. Knol, D. Lu, and M. Traylor report no disclosures relevant to the manuscript. H.H.H. Adams is supported by ZonMW grant 916.19.151. J.R.J. Romero, A.V. Smith, M. Fornage, E. Hofer, and J. Liu report no disclosures relevant to the manuscript. I.C. Hostettler received funding from the Alzheimer Research UK and Dunhill Medical Trust Foundation. M. Luciano, S. Trompet, A.-K. Giese, S. Hilal, E.B. van den Akker, D. Vojinovic, S. Li, S. Sigurdsson, S.J. van der Lee, and C.R. Jack, Jr. report no disclosures relevant to the manuscript. D. Wilson received funding from the Stroke Foundation/British Heart Foundation. P. Yilmaz, C.L. Satizabal, D.C.M. Liewald, J. van der Grond, C. Chen, Y. Saba, A. van der Lugt, M.E. Bastin, B.G. Windham, C.Y. Cheng, L. Pirpamer, K. Kantarci, J.J. Himali, Q. Yang, Z. Morris, A.S. Beiser, D.J. Tozer, M.W. Vernooij, N. Amin, M. Beekman, J.Y. Koh, and D.J. Stott report no disclosures relevant to the manuscript. H. Houlden received funding from the Alzheimer Research UK and Dunhill Medical Trust Foundation. R. Schmidt, R.F. Gottesman, and A.D. MacKinnon report no disclosures relevant to the manuscript. C. DeCarli is supported by the Alzheimer's Disease Center (P30 AG 010129) and serves as a consultant of Novartis Pharmaceuticals. V. Gudnason, I.J. Deary, C.M. van Duijn, P.E. Slagboom, T.Y. Wong, and N.S. Rost report no disclosures relevant to the manuscript. J.W. Jukema is an Established Clinical Investigator of the Netherlands Heart Foundation (grant 2001 D 032). T.H. Mosley reports no disclosures relevant to the manuscript. D.J. Werring received funding from the Stroke Foundation/British Heart Foundation. H. Schmidt, J.M. Wardlaw, M.A. Ikram, S. Seshadri, L.J. Launer, and H.S. Markus report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures. Publisher Copyright: Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
dc.description.abstract OBJECTIVE: To identify common genetic variants associated with the presence of brain microbleeds (BMBs). METHODS: We performed genome-wide association studies in 11 population-based cohort studies and 3 case-control or case-only stroke cohorts. Genotypes were imputed to the Haplotype Reference Consortium or 1000 Genomes reference panel. BMBs were rated on susceptibility-weighted or T2*-weighted gradient echo MRI sequences, and further classified as lobar or mixed (including strictly deep and infratentorial, possibly with lobar BMB). In a subset, we assessed the effects of APOE ε2 and ε4 alleles on BMB counts. We also related previously identified cerebral small vessel disease variants to BMBs. RESULTS: BMBs were detected in 3,556 of the 25,862 participants, of which 2,179 were strictly lobar and 1,293 mixed. One locus in the APOE region reached genome-wide significance for its association with BMB (lead single nucleotide polymorphism rs769449; odds ratio [OR]any BMB [95% confidence interval (CI)] 1.33 [1.21-1.45]; p = 2.5 × 10-10). APOE ε4 alleles were associated with strictly lobar (OR [95% CI] 1.34 [1.19-1.50]; p = 1.0 × 10-6) but not with mixed BMB counts (OR [95% CI] 1.04 [0.86-1.25]; p = 0.68). APOE ε2 alleles did not show associations with BMB counts. Variants previously related to deep intracerebral hemorrhage and lacunar stroke, and a risk score of cerebral white matter hyperintensity variants, were associated with BMB. CONCLUSIONS: Genetic variants in the APOE region are associated with the presence of BMB, most likely due to the APOE ε4 allele count related to a higher number of strictly lobar BMBs. Genetic predisposition to small vessel disease confers risk of BMB, indicating genetic overlap with other cerebral small vessel disease markers.
dc.format.extent e3331-e3343
dc.language.iso en
dc.relation.ispartofseries Neurology; 95(24)
dc.rights info:eu-repo/semantics/openAccess
dc.subject Heilablóðfall
dc.subject Erfðafræði
dc.subject Apolipoprotein E4 / genetics
dc.subject CerebralHemorrhage / genetics
dc.subject Cerebral Hemorrhage / pathology
dc.subject Cerebral Small Vessel Diseases / genetics
dc.subject Genome-Wide Association Study
dc.subject White Matter / pathology
dc.subject Neurology (clinical)
dc.title Association of common genetic variants with brain microbleeds : A genome-wide association study
dc.type /dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article
dc.description.version Peer reviewed
dc.identifier.pmid 32913026
dc.identifier.doi https://doi.org/10.1212/WNL.0000000000010852
dc.relation.url http://www.scopus.com/inward/record.url?scp=85098521230&partnerID=8YFLogxK
dc.contributor.department Faculty of Medicine


Files in this item

This item appears in the following Collection(s)

Show simple item record