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Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting.

Publication ,  Journal Article
Chauhan, G; Adams, HHH; Satizabal, CL; Bis, JC; Teumer, A; Sargurupremraj, M; Hofer, E; Trompet, S; Hilal, S; Smith, AV; Jian, X; Malik, R ...
Published in: Neurology
January 28, 2019

OBJECTIVE: To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. METHODS: We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI. RESULTS: The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10-8; and LINC00539/ZDHHC20, p = 5.82 × 10-9. Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p [BI] = 9.38 × 10-25; p [SSBI] = 5.23 × 10-14 for hypertension), smoking (p [BI] = 4.4 × 10-10; p [SSBI] = 1.2 × 10-4), diabetes (p [BI] = 1.7 × 10-8; p [SSBI] = 2.8 × 10-3), previous cardiovascular disease (p [BI] = 1.0 × 10-18; p [SSBI] = 2.3 × 10-7), stroke (p [BI] = 3.9 × 10-69; p [SSBI] = 3.2 × 10-24), and MRI-defined white matter hyperintensity burden (p [BI] = 1.43 × 10-157; p [SSBI] = 3.16 × 10-106), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p ≤ 0.0022), without indication of directional pleiotropy. CONCLUSION: In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI.

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Published In

Neurology

DOI

EISSN

1526-632X

Publication Date

January 28, 2019

Volume

92

Issue

5

Start / End Page

e486 / e503

Location

United States

Related Subject Headings

  • Neurology & Neurosurgery
  • 3209 Neurosciences
  • 3202 Clinical sciences
  • 1702 Cognitive Sciences
  • 1109 Neurosciences
  • 1103 Clinical Sciences
 

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Chicago
ICMJE
MLA
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Chauhan, G., Adams, H. H. H., Satizabal, C. L., Bis, J. C., Teumer, A., Sargurupremraj, M., … Stroke Genetics Network (SiGN), the International Stroke Genetics Consortium (ISGC), METASTROKE, Alzheimer’s Disease Genetics Consortium (ADGC), and the Neurology Working Group of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, . (2019). Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting. Neurology, 92(5), e486–e503. https://doi.org/10.1212/WNL.0000000000006851
Chauhan, Ganesh, Hieab H. H. Adams, Claudia L. Satizabal, Joshua C. Bis, Alexander Teumer, Muralidharan Sargurupremraj, Edith Hofer, et al. “Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting.Neurology 92, no. 5 (January 28, 2019): e486–503. https://doi.org/10.1212/WNL.0000000000006851.
Chauhan G, Adams HHH, Satizabal CL, Bis JC, Teumer A, Sargurupremraj M, et al. Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting. Neurology. 2019 Jan 28;92(5):e486–503.
Chauhan, Ganesh, et al. “Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting.Neurology, vol. 92, no. 5, Jan. 2019, pp. e486–503. Pubmed, doi:10.1212/WNL.0000000000006851.
Chauhan G, Adams HHH, Satizabal CL, Bis JC, Teumer A, Sargurupremraj M, Hofer E, Trompet S, Hilal S, Smith AV, Jian X, Malik R, Traylor M, Pulit SL, Amouyel P, Mazoyer B, Zhu Y-C, Kaffashian S, Schilling S, Beecham GW, Montine TJ, Schellenberg GD, Kjartansson O, Guðnason V, Knopman DS, Griswold ME, Windham BG, Gottesman RF, Mosley TH, Schmidt R, Saba Y, Schmidt H, Takeuchi F, Yamaguchi S, Nabika T, Kato N, Rajan KB, Aggarwal NT, De Jager PL, Evans DA, Psaty BM, Rotter JI, Rice K, Lopez OL, Liao J, Chen C, Cheng C-Y, Wong TY, Ikram MK, van der Lee SJ, Amin N, Chouraki V, DeStefano AL, Aparicio HJ, Romero JR, Maillard P, DeCarli C, Wardlaw JM, Hernández MDCV, Luciano M, Liewald D, Deary IJ, Starr JM, Bastin ME, Muñoz Maniega S, Slagboom PE, Beekman M, Deelen J, Uh H-W, Lemmens R, Brodaty H, Wright MJ, Ames D, Boncoraglio GB, Hopewell JC, Beecham AH, Blanton SH, Wright CB, Sacco RL, Wen W, Thalamuthu A, Armstrong NJ, Chong E, Schofield PR, Kwok JB, van der Grond J, Stott DJ, Ford I, Jukema JW, Vernooij MW, Hofman A, Uitterlinden AG, van der Lugt A, Wittfeld K, Grabe HJ, Hosten N, von Sarnowski B, Völker U, Levi C, Jimenez-Conde J, Sharma P, Sudlow CLM, Rosand J, Woo D, Cole JW, Meschia JF, Slowik A, Thijs V, Lindgren A, Melander O, Grewal RP, Rundek T, Rexrode K, Rothwell PM, Arnett DK, Jern C, Johnson JA, Benavente OR, Wasssertheil-Smoller S, Lee J-M, Wong Q, Mitchell BD, Rich SS, McArdle PF, Geerlings MI, van der Graaf Y, de Bakker PIW, Asselbergs FW, Srikanth V, Thomson R, McWhirter R, Moran C, Callisaya M, Phan T, Rutten-Jacobs LCA, Bevan S, Tzourio C, Mather KA, Sachdev PS, van Duijn CM, Worrall BB, Dichgans M, Kittner SJ, Markus HS, Ikram MA, Fornage M, Launer LJ, Seshadri S, Longstreth WT, Debette S, Stroke Genetics Network (SiGN), the International Stroke Genetics Consortium (ISGC), METASTROKE, Alzheimer’s Disease Genetics Consortium (ADGC), and the Neurology Working Group of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting. Neurology. 2019 Jan 28;92(5):e486–e503.

Published In

Neurology

DOI

EISSN

1526-632X

Publication Date

January 28, 2019

Volume

92

Issue

5

Start / End Page

e486 / e503

Location

United States

Related Subject Headings

  • Neurology & Neurosurgery
  • 3209 Neurosciences
  • 3202 Clinical sciences
  • 1702 Cognitive Sciences
  • 1109 Neurosciences
  • 1103 Clinical Sciences