Dataset Information

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

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.

SUBMITTER: Knol MJ

PROVIDER: S-EPMC7836652 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

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

Knol Maria J MJ Lu Dongwei D Traylor Matthew M Adams Hieab H H HHH Romero José Rafael J JRJ Smith Albert V AV Fornage Myriam M Hofer Edith E Liu Junfeng J Hostettler Isabel C IC Luciano Michelle M Trompet Stella S Giese Anne-Katrin AK Hilal Saima S van den Akker Erik B EB Vojinovic Dina D Li Shuo S Sigurdsson Sigurdur S van der Lee Sven J SJ Jack Clifford R CR Wilson Duncan D Yilmaz Pinar P Satizabal Claudia L CL Liewald David C M DCM van der Grond Jeroen J Chen Christopher C Saba Yasaman Y van der Lugt Aad A Bastin Mark E ME Windham B Gwen BG Cheng Ching Yu CY Pirpamer Lukas L Kantarci Kejal K Himali Jayandra J JJ Yang Qiong Q Morris Zoe Z Beiser Alexa S AS Tozer Daniel J DJ Vernooij Meike W MW Amin Najaf N Beekman Marian M Koh Jia Yu JY Stott David J DJ Houlden Henry H Schmidt Reinhold R Gottesman Rebecca F RF MacKinnon Andrew D AD DeCarli Charles C Gudnason Vilmundur V Deary Ian J IJ van Duijn Cornelia M CM Slagboom P Eline PE Wong Tien Yin TY Rost Natalia S NS Jukema J Wouter JW Mosley Thomas H TH Werring David J DJ Schmidt Helena H Wardlaw Joanna M JM Ikram M Arfan MA Seshadri Sudha S Launer Lenore J LJ Markus Hugh S HS

Neurology 20200910 24

<h4>Objective</h4>To identify common genetic variants associated with the presence of brain microbleeds (BMBs).<h4>Methods</h4>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 ...[more]

PMID: 32913026

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Dataset Information

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

Objective

Methods

Results

Conclusions

Publications

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

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