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In this study, we performed a two\u2010sample Mendelian randomization (MR) analysis with individual\u2010level data by defining two nonoverlapping sets of European ancestry individuals (genetics\u2013exposure set: <jats:italic>N<\/jats:italic>\u2009=\u2009203,111; mean age\u2009=\u200956.71\u2009years, genetics\u2013outcome set: <jats:italic>N<\/jats:italic>\u2009=\u200916,156; mean age\u2009=\u200954.61\u2009years) from UK Biobank to evaluate the causal effects of BP on regional WM integrity, measured by fractional anisotropy of diffusion tensor imaging. Two BP traits: systolic and diastolic blood pressure were used as exposures. Genetic variant was carefully selected as instrumental variable (IV) under the MR analysis assumptions. We existing large\u2010scale genome\u2010wide association study summary data for validation. The main method used was a generalized version of inverse\u2010variance weight method while other MR methods were also applied for consistent findings. Two additional MR analyses were performed to exclude the possibility of reverse causality. We found significantly negative causal effects (FDR\u2010adjusted <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05; every 10\u2009mmHg increase in BP leads to a decrease in FA value by .4%\u2009~\u20092%) of BP traits on a union set of 17 WM tracts, including brain regions related to cognitive function and memory. Our study extended the previous findings of association to causation for regional WM integrity, providing insights into the pathological processes of elevated BP that might chronically alter the brain microstructure in different regions.<\/jats:p>","DOI":"10.1002\/jnr.25205","type":"journal-article","created":{"date-parts":[[2023,6,18]],"date-time":"2023-06-18T14:29:50Z","timestamp":1687098590000},"page":"1471-1483","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Deciphering the causal relationship between blood pressure and regional white matter integrity: A two\u2010sample Mendelian randomization study"],"prefix":"10.1002","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6530-1088","authenticated-orcid":false,"given":"Zhenyao","family":"Ye","sequence":"first","affiliation":[{"name":"Maryland Psychiatric Research Center, Department of Psychiatry, School of Medicine University of Maryland  Baltimore Maryland USA"},{"name":"Division of Biostatistics and Bioinformatics, Department of Epidemiology and Public Health, School of Medicine University of Maryland  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Mo","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Computer Science and Technology Qilu University of Technology (Shandong Academy of Sciences)  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4473-1142","authenticated-orcid":false,"given":"Si","family":"Gao","sequence":"additional","affiliation":[{"name":"Maryland Psychiatric Research Center, Department of Psychiatry, School of Medicine University of Maryland  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Science, College of Agriculture &amp; Natural Resources University of Maryland  College Park Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health University of Maryland  College Park Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis","family":"Canida","sequence":"additional","affiliation":[{"name":"Department of Mathematics, The College of Computer, Mathematical, and Natural Sciences University of Maryland  College Park Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Chia","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health University of Maryland  College Park Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn S.","family":"Hatch","sequence":"additional","affiliation":[{"name":"Maryland Psychiatric Research Center, Department of Psychiatry, School of Medicine University of Maryland  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhou","family":"Ma","sequence":"additional","affiliation":[{"name":"Maryland Psychiatric Research Center, Department of Psychiatry, School of Medicine University of Maryland  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Braxton D.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. 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