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

To identify common genetic variants associated with the presence of brain microbleeds (BMBs). 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 Genome...

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Podrobná bibliografia
Vydané v:	Neurology Ročník 95; číslo 24; s. e3331
Hlavní autori:	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, Jr, 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
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 15.12.2020
Predmet:	Aged Aged, 80 and over Alleles Apolipoprotein E2 - genetics Apolipoprotein E4 - genetics Apolipoproteins E - genetics Case-Control Studies Cerebral Hemorrhage - diagnostic imaging Cerebral Hemorrhage - epidemiology Cerebral Hemorrhage - genetics Cerebral Hemorrhage - pathology Cerebral Small Vessel Diseases - epidemiology Cerebral Small Vessel Diseases - genetics Cohort Studies Female Genetic Predisposition to Disease Genome-Wide Association Study Humans Magnetic Resonance Imaging Male Middle Aged Polymorphism, Single Nucleotide Risk White Matter - diagnostic imaging White Matter - pathology
ISSN:	1526-632X, 1526-632X
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Popis
Shrnutí:	To identify common genetic variants associated with the presence of brain microbleeds (BMBs). 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 ε2 and ε4 alleles on BMB counts. We also related previously identified cerebral small vessel disease variants to BMBs. 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 region reached genome-wide significance for its association with BMB (lead rs769449; odds ratio [OR] [95% confidence interval (CI)] 1.33 [1.21-1.45]; = 2.5 × 10 ). ε4 alleles were associated with strictly lobar (OR [95% CI] 1.34 [1.19-1.50]; = 1.0 × 10 ) but not with mixed BMB counts (OR [95% CI] 1.04 [0.86-1.25]; = 0.68). 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. Genetic variants in the region are associated with the presence of BMB, most likely due to the 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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1526-632X 1526-632X
DOI:	10.1212/WNL.0000000000010852