Knol, Maria J; Lu, Dongwei; Traylor, Matthew; Adams, Hieab H H; Romero, José Rafael J; Smith, Albert V; Fornage, Myriam; Hofer, Edith; Liu, Junfeng; Hostettler, Isabel C; Luciano, Michelle; Trompet, Stella; Giese, Anne-Katrin; Hilal, Saima; van den Akker, Erik B; Vojinovic, Dina; Li, Shuo; Sigurdsson, Sigurdur; van der Lee, Sven J; Jack, Clifford R; Wilson, Duncan; Yilmaz, Pinar; Satizabal, Claudia L; Liewald, David C M; van der Grond, Jeroen; Chen, Christopher; Saba, Yasaman; van der Lugt, Aad; Bastin, Mark E; Windham, B Gwen; Cheng, Ching Yu; Pirpamer, Lukas; Kantarci, Kejal; Himali, Jayandra J; Yang, Qiong; Morris, Zoe; Beiser, Alexa S; Tozer, Daniel J; Vernooij, Meike W; Amin, Najaf; Beekman, Marian; Koh, Jia Yu; Stott, David J; Houlden, Henry; Schmidt, Reinhold; Gottesman, Rebecca F; MacKinnon, Andrew D; DeCarli, Charles; Gudnason, Vilmundur; Deary, Ian J; van Duijn, Cornelia M; Slagboom, P Eline; Wong, Tien Yin; Rost, Natalia S; Jukema, J Wouter; Mosley, Thomas H; Werring, David J; Schmidt, Helena; Wardlaw, Joanna M; Ikram, M Arfan; Seshadri, Sudha; Launer, Lenore J; Markus, Hugh S     «

Knol, Maria J; Lu, Dongwei; Traylor, Matthew; Adams, Hieab H H; Romero, José Rafael J; Smith, Albert V; Fornage, Myriam; Hofer, Edith; Liu, Junfeng; Hostettler, Isabel C; Luciano, Michelle; Trompet, Stella; Giese, Anne-Katrin; Hilal, Saima; van den Akker, Erik B; Vojinovic, Dina; Li, Shuo; Sigurdsson, Sigurdur; van der Lee, Sven J; Jack, Clifford R; Wilson, Duncan; Yilmaz, Pinar; Satizabal, Claudia L; Liewald, David C M; van der Grond, Jeroen; Chen, Christopher; Saba, Yasaman; van der Lugt, Aad;...     »

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.      «

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 inf...     »