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

Chauhan, G., Adams, H. H. H., Satizabal, C. L., Bis, J. C., Teumer, A., Sargurupremraj, M., Hofer, E., Trompet, S., Hilal, S., Smith, A. V., Jian, X., Malik, R., Traylor, M., Pulit, S. L., Amouyel, P., Mazoyer, B., Zhu, Y. C., Kaffashian, S., Schilling, S., Beecham, G. W., Montine, T. J., Schellenberg, G. D., Kjartansson, O., Guethnason, V., Knopman, D. S., Griswold, M. E., Windham, B. G., Gottesman, R. F., Mosley, T. H., Schmidt, R., Saba, Y., Schmidt, H., Takeuchi, F., Yamaguchi, S., Nabika, T., Kato, N., Rajan, K. B., Aggarwal, N. T., De Jager, P. L., Evans, D. A., Psaty, B. M., Rotter, J. I., Rice, K., Lopez, O. L., Liao, J., Chen, C., Cheng, C. Y., Wong, T. Y., Ikram, M. K., van der Lee, S. J., Amin, N., Chouraki, V., DeStefano, A. L., Aparicio, H. J., Romero, J. R., Maillard, P., DeCarli, C., Wardlaw, J. M., Hernandez, M., Luciano, M., Liewald, D., Deary, I. J., Starr, J. M., Bastin, M. E., Munoz Maniega, S., Slagboom, P. E., Beekman, M., Deelen, J., Uh, H. W., Lemmens, R., Brodaty, H., Wright, M. J., Ames, D., Boncoraglio, G. B., Hopewell, J. C., Beecham, A. H., Blanton, S. H., Wright, C. B., Sacco, R. L., Wen, W., Thalamuthu, A., Armstrong, N. J., Chong, E., Schofield, P. R., Kwok, J. B., van der Grond, J., Stott, D. J., Ford, I., Jukema, J. W., Vernooij, M. W., Hofman, A., Uitterlinden, A. G., van der Lugt, A., Wittfeld, K., Grabe, H. J., Hosten, N., von Sarnowski, B., Volker, U., Levi, C., Jimenez-Conde, J., Sharma, P., Sudlow, C. L. M., Rosand, J., Woo, D., Cole, J. W., Meschia, J. F., Slowik, A., Thijs, V., Lindgren, A., Melander, O., Grewal, R. P., Rundek, T., Rexrode, K., Rothwell, P. M., Arnett, D. K., Jern, C., Johnson, J. A., Benavente, O. R., Wasssertheil-Smoller, S., Lee, J. M., Wong, Q., Mitchell, B. D., Rich, S. S., McArdle, P. F., Geerlings, M. I., van der Graaf, Y., de Bakker, P. I. W., Asselbergs, F. W., Srikanth, V., Thomson, R., McWhirter, R., Moran, C., Callisaya, M., Phan, T., Rutten-Jacobs, L. C. A., Bevan, S., Tzourio, C., Mather, K. A., Sachdev, P. S., van Duijn, C. M., Worrall, B. B., Dichgans, M., Kittner, S. J., Markus, H. S., Ikram, M. A., Fornage, M., Launer, L. J., Seshadri, S., Longstreth, W. T. J., Debette, S., Stroke Genetics Network, t. I. S. G. C. M. A. D. G. C., the Neurology Working Group of the Cohorts for, H., & Aging Research in Genomic Epidemiology, C. (2019). Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting. Neurology, 5(92), e486-e503. doi:10.1212/WNL.0000000000006851.

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アイテムのパーマリンク: https://hdl.handle.net/21.11116/0000-000B-4315-2 版のパーマリンク: https://hdl.handle.net/21.11116/0000-000B-4316-1
資料種別: 学術論文

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関連URL

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URL:
https://www.ncbi.nlm.nih.gov/pubmed/30651383 (全文テキスト（全般）)
説明:
-
OA-Status:
Not specified

作成者

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 作成者:
Chauhan, G., 著者
Adams, H. H. H., 著者
Satizabal, C. L., 著者
Bis, J. C., 著者
Teumer, A., 著者
Sargurupremraj, M., 著者
Hofer, E., 著者
Trompet, S., 著者
Hilal, S., 著者
Smith, A. V., 著者
Jian, X., 著者
Malik, R., 著者
Traylor, M., 著者
Pulit, S. L., 著者
Amouyel, P., 著者
Mazoyer, B., 著者
Zhu, Y. C., 著者
Kaffashian, S., 著者
Schilling, S., 著者
Beecham, G. W., 著者
Montine, T. J., 著者Schellenberg, G. D., 著者Kjartansson, O., 著者Guethnason, V., 著者Knopman, D. S., 著者Griswold, M. E., 著者Windham, B. G., 著者Gottesman, R. F., 著者Mosley, T. H., 著者Schmidt, R., 著者Saba, Y., 著者Schmidt, H., 著者Takeuchi, F., 著者Yamaguchi, S., 著者Nabika, T., 著者Kato, N., 著者Rajan, K. B., 著者Aggarwal, N. T., 著者De Jager, P. L., 著者Evans, D. A., 著者Psaty, B. M., 著者Rotter, J. I., 著者Rice, K., 著者Lopez, O. L., 著者Liao, J., 著者Chen, C., 著者Cheng, C. Y., 著者Wong, T. Y., 著者Ikram, M. K., 著者van der Lee, S. J., 著者Amin, N., 著者Chouraki, V., 著者DeStefano, A. L., 著者Aparicio, H. J., 著者Romero, J. R., 著者Maillard, P., 著者DeCarli, C., 著者Wardlaw, J. M., 著者Hernandez, Mdcv, 著者Luciano, M., 著者Liewald, D., 著者Deary, I. J., 著者Starr, J. M., 著者Bastin, M. E., 著者Munoz Maniega, S., 著者Slagboom, P. E., 著者Beekman, M., 著者Deelen, J.1, 著者           Uh, H. W., 著者Lemmens, R., 著者Brodaty, H., 著者Wright, M. J., 著者Ames, D., 著者Boncoraglio, G. B., 著者Hopewell, J. C., 著者Beecham, A. H., 著者Blanton, S. H., 著者Wright, C. B., 著者Sacco, R. L., 著者Wen, W., 著者Thalamuthu, A., 著者Armstrong, N. J., 著者Chong, E., 著者Schofield, P. R., 著者Kwok, J. B., 著者van der Grond, J., 著者Stott, D. J., 著者Ford, I., 著者Jukema, J. W., 著者Vernooij, M. W., 著者Hofman, A., 著者Uitterlinden, A. G., 著者van der Lugt, A., 著者Wittfeld, K., 著者Grabe, H. J., 著者Hosten, N., 著者von Sarnowski, B., 著者Volker, U., 著者Levi, C., 著者Jimenez-Conde, J., 著者Sharma, P., 著者Sudlow, C. L. M., 著者Rosand, J., 著者Woo, D., 著者Cole, J. W., 著者Meschia, J. F., 著者Slowik, A., 著者Thijs, V., 著者Lindgren, A., 著者Melander, O., 著者Grewal, R. P., 著者Rundek, T., 著者Rexrode, K., 著者Rothwell, P. M., 著者Arnett, D. K., 著者Jern, C., 著者Johnson, J. A., 著者Benavente, O. R., 著者Wasssertheil-Smoller, S., 著者Lee, J. M., 著者Wong, Q., 著者Mitchell, B. D., 著者Rich, S. S., 著者McArdle, P. F., 著者Geerlings, M. I., 著者van der Graaf, Y., 著者de Bakker, P. I. W., 著者Asselbergs, F. W., 著者Srikanth, V., 著者Thomson, R., 著者McWhirter, R., 著者Moran, C., 著者Callisaya, M., 著者Phan, T., 著者Rutten-Jacobs, L. C. A., 著者Bevan, S., 著者Tzourio, C., 著者Mather, K. A., 著者Sachdev, P. S., 著者van Duijn, C. M., 著者Worrall, B. B., 著者Dichgans, M., 著者Kittner, S. J., 著者Markus, H. S., 著者Ikram, M. A., 著者Fornage, M., 著者Launer, L. J., 著者Seshadri, S., 著者Longstreth, W. T., Jr., 著者Debette, S., 著者Stroke Genetics Network, the International Stroke Genetics Consortium Metastroke Alzheimer's Disease Genetics Consortium, 著者the Neurology Working Group of the Cohorts for, Heart, 著者Aging Research in Genomic Epidemiology, Consortium, 著者 全て表示
所属:
1Deelen – Genetics and Biomarkers of Human Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_3394006              

内容説明

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キーワード: -
 要旨: 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 x 10(-8); and LINC00539/ZDHHC20, p = 5.82 x 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 x 10(-25); p [SSBI] = 5.23 x 10(-14) for hypertension), smoking (p [BI] = 4.4 x 10(-10); p [SSBI] = 1.2 x 10(-4)), diabetes (p [BI] = 1.7 x 10(-8); p [SSBI] = 2.8 x 10(-3)), previous cardiovascular disease (p [BI] = 1.0 x 10(-18); p [SSBI] = 2.3 x 10(-7)), stroke (p [BI] = 3.9 x 10(-69); p [SSBI] = 3.2 x 10(-24)), and MRI-defined white matter hyperintensity burden (p [BI] = 1.43 x 10(-157); p [SSBI] = 3.16 x 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.

資料詳細

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 日付: 2019-01-162019-01-18
 出版の状態: 出版
 ページ: -
 出版情報: -
 目次: -
 査読: -
 識別子（DOI, ISBNなど）: その他: 30651383
DOI: 10.1212/WNL.0000000000006851
ISSN: 1526-632X (Electronic)0028-3878 (Linking)
 学位: -

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出版物 1

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出版物名: Neurology
種別: 学術雑誌
 著者・編者:
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出版社, 出版地: -
ページ: - 巻号: 5 (92) 通巻号: - 開始・終了ページ: e486 - e503 識別子（ISBN, ISSN, DOIなど）: -