Genes From a Translational Analysis Support a Multifactorial Nature of White Matter Hyperintensities
BACKGROUND AND PURPOSE—White matter hyperintensities (WMH) of presumed vascular origin increase the risk of stroke and dementia. Despite strong WMH heritability, few gene associations have been identified. Relevant experimental models may be informative. METHODS—We tested the associations between ge...
Saved in:
| Published in | Stroke (1970) Vol. 46; no. 2; pp. 341 - 347 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Heart Association, Inc
01.02.2015
Lippincott Williams & Wilkins |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0039-2499 1524-4628 1524-4628 |
| DOI | 10.1161/STROKEAHA.114.007649 |
Cover
Loading…
| Abstract | BACKGROUND AND PURPOSE—White matter hyperintensities (WMH) of presumed vascular origin increase the risk of stroke and dementia. Despite strong WMH heritability, few gene associations have been identified. Relevant experimental models may be informative.
METHODS—We tested the associations between genes that were differentially expressed in brains of young spontaneously hypertensive stroke–prone rats and human WMH (using volume and visual score) in 621 subjects from the Lothian Birth Cohort 1936 (LBC1936). We then attempted replication in 9361 subjects from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE). We also tested the subjects from LBC1936 for previous genome-wide WMH associations found in subjects from CHARGE.
RESULTS—Of 126 spontaneously hypertensive stroke–prone rat genes, 10 were nominally associated with WMH volume or score in subjects from LBC1936, of which 5 (AFP, ALB, GNAI1, RBM8a, and MRPL18) were associated with both WMH volume and score (P<0.05); 2 of the 10 (XPNPEP1, P=6.7×10; FARP1, P=0.024) plus another spontaneously hypertensive stroke–prone rat gene (USMG5, P=0.00014), on chromosomes 10, 13, and 10 respectively, were associated with WMH in subjects from CHARGE. Gene set enrichment showed significant associations for downregulated spontaneously hypertensive stroke–prone rat genes with WMH in humans. In subjects from LBC1936, we replicated CHARGE’s genome-wide WMH associations on chromosomes 17 (TRIM65 and TRIM47) and, for the first time, 1 (PMF1).
CONCLUSIONS—Despite not passing multiple testing thresholds individually, these genes collectively are relevant to known WMH associations, proposed WMH mechanisms, or dementiaassociations with Alzheimerʼs disease, late-life depression, ATP production, osmotic regulation, neurodevelopmental abnormalities, and cognitive impairment. If replicated further, they suggest a multifactorial nature for WMH and argue for more consideration of vascular contributions to dementia. |
|---|---|
| AbstractList | White matter hyperintensities (WMH) of presumed vascular origin increase the risk of stroke and dementia. Despite strong WMH heritability, few gene associations have been identified. Relevant experimental models may be informative.
We tested the associations between genes that were differentially expressed in brains of young spontaneously hypertensive stroke-prone rats and human WMH (using volume and visual score) in 621 subjects from the Lothian Birth Cohort 1936 (LBC1936). We then attempted replication in 9361 subjects from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE). We also tested the subjects from LBC1936 for previous genome-wide WMH associations found in subjects from CHARGE.
Of 126 spontaneously hypertensive stroke-prone rat genes, 10 were nominally associated with WMH volume or score in subjects from LBC1936, of which 5 (AFP, ALB, GNAI1, RBM8a, and MRPL18) were associated with both WMH volume and score (P<0.05); 2 of the 10 (XPNPEP1, P=6.7×10(-5); FARP1, P=0.024) plus another spontaneously hypertensive stroke-prone rat gene (USMG5, P=0.00014), on chromosomes 10, 13, and 10 respectively, were associated with WMH in subjects from CHARGE. Gene set enrichment showed significant associations for downregulated spontaneously hypertensive stroke-prone rat genes with WMH in humans. In subjects from LBC1936, we replicated CHARGE's genome-wide WMH associations on chromosomes 17 (TRIM65 and TRIM47) and, for the first time, 1 (PMF1).
Despite not passing multiple testing thresholds individually, these genes collectively are relevant to known WMH associations, proposed WMH mechanisms, or dementia: associations with Alzheimer's disease, late-life depression, ATP production, osmotic regulation, neurodevelopmental abnormalities, and cognitive impairment. If replicated further, they suggest a multifactorial nature for WMH and argue for more consideration of vascular contributions to dementia. Supplemental Digital Content is available in the text. White matter hyperintensities (WMH) of presumed vascular origin increase the risk of stroke and dementia. Despite strong WMH heritability, few gene associations have been identified. Relevant experimental models may be informative.BACKGROUND AND PURPOSEWhite matter hyperintensities (WMH) of presumed vascular origin increase the risk of stroke and dementia. Despite strong WMH heritability, few gene associations have been identified. Relevant experimental models may be informative.We tested the associations between genes that were differentially expressed in brains of young spontaneously hypertensive stroke-prone rats and human WMH (using volume and visual score) in 621 subjects from the Lothian Birth Cohort 1936 (LBC1936). We then attempted replication in 9361 subjects from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE). We also tested the subjects from LBC1936 for previous genome-wide WMH associations found in subjects from CHARGE.METHODSWe tested the associations between genes that were differentially expressed in brains of young spontaneously hypertensive stroke-prone rats and human WMH (using volume and visual score) in 621 subjects from the Lothian Birth Cohort 1936 (LBC1936). We then attempted replication in 9361 subjects from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE). We also tested the subjects from LBC1936 for previous genome-wide WMH associations found in subjects from CHARGE.Of 126 spontaneously hypertensive stroke-prone rat genes, 10 were nominally associated with WMH volume or score in subjects from LBC1936, of which 5 (AFP, ALB, GNAI1, RBM8a, and MRPL18) were associated with both WMH volume and score (P<0.05); 2 of the 10 (XPNPEP1, P=6.7×10(-5); FARP1, P=0.024) plus another spontaneously hypertensive stroke-prone rat gene (USMG5, P=0.00014), on chromosomes 10, 13, and 10 respectively, were associated with WMH in subjects from CHARGE. Gene set enrichment showed significant associations for downregulated spontaneously hypertensive stroke-prone rat genes with WMH in humans. In subjects from LBC1936, we replicated CHARGE's genome-wide WMH associations on chromosomes 17 (TRIM65 and TRIM47) and, for the first time, 1 (PMF1).RESULTSOf 126 spontaneously hypertensive stroke-prone rat genes, 10 were nominally associated with WMH volume or score in subjects from LBC1936, of which 5 (AFP, ALB, GNAI1, RBM8a, and MRPL18) were associated with both WMH volume and score (P<0.05); 2 of the 10 (XPNPEP1, P=6.7×10(-5); FARP1, P=0.024) plus another spontaneously hypertensive stroke-prone rat gene (USMG5, P=0.00014), on chromosomes 10, 13, and 10 respectively, were associated with WMH in subjects from CHARGE. Gene set enrichment showed significant associations for downregulated spontaneously hypertensive stroke-prone rat genes with WMH in humans. In subjects from LBC1936, we replicated CHARGE's genome-wide WMH associations on chromosomes 17 (TRIM65 and TRIM47) and, for the first time, 1 (PMF1).Despite not passing multiple testing thresholds individually, these genes collectively are relevant to known WMH associations, proposed WMH mechanisms, or dementia: associations with Alzheimer's disease, late-life depression, ATP production, osmotic regulation, neurodevelopmental abnormalities, and cognitive impairment. If replicated further, they suggest a multifactorial nature for WMH and argue for more consideration of vascular contributions to dementia.CONCLUSIONSDespite not passing multiple testing thresholds individually, these genes collectively are relevant to known WMH associations, proposed WMH mechanisms, or dementia: associations with Alzheimer's disease, late-life depression, ATP production, osmotic regulation, neurodevelopmental abnormalities, and cognitive impairment. If replicated further, they suggest a multifactorial nature for WMH and argue for more consideration of vascular contributions to dementia. BACKGROUND AND PURPOSE—White matter hyperintensities (WMH) of presumed vascular origin increase the risk of stroke and dementia. Despite strong WMH heritability, few gene associations have been identified. Relevant experimental models may be informative. METHODS—We tested the associations between genes that were differentially expressed in brains of young spontaneously hypertensive stroke–prone rats and human WMH (using volume and visual score) in 621 subjects from the Lothian Birth Cohort 1936 (LBC1936). We then attempted replication in 9361 subjects from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE). We also tested the subjects from LBC1936 for previous genome-wide WMH associations found in subjects from CHARGE. RESULTS—Of 126 spontaneously hypertensive stroke–prone rat genes, 10 were nominally associated with WMH volume or score in subjects from LBC1936, of which 5 (AFP, ALB, GNAI1, RBM8a, and MRPL18) were associated with both WMH volume and score (P<0.05); 2 of the 10 (XPNPEP1, P=6.7×10; FARP1, P=0.024) plus another spontaneously hypertensive stroke–prone rat gene (USMG5, P=0.00014), on chromosomes 10, 13, and 10 respectively, were associated with WMH in subjects from CHARGE. Gene set enrichment showed significant associations for downregulated spontaneously hypertensive stroke–prone rat genes with WMH in humans. In subjects from LBC1936, we replicated CHARGE’s genome-wide WMH associations on chromosomes 17 (TRIM65 and TRIM47) and, for the first time, 1 (PMF1). CONCLUSIONS—Despite not passing multiple testing thresholds individually, these genes collectively are relevant to known WMH associations, proposed WMH mechanisms, or dementiaassociations with Alzheimerʼs disease, late-life depression, ATP production, osmotic regulation, neurodevelopmental abnormalities, and cognitive impairment. If replicated further, they suggest a multifactorial nature for WMH and argue for more consideration of vascular contributions to dementia. |
| Author | Debette, Stephanie McBride, Martin Lopez, Lorna M. Hill, W. David Graham, Delyth McClure, John Bis, Joshua C. Deary, Ian J. Smith, Colin Launer, Lenore Porteous, David J. Ikram, M. Arfan Seshadri, Sudha Harris, Sarah E. Dominiczak, Anna Schmidt, Reinhold Yang, Qiong Munoz Maniega, Susana Bailey, Emma Bastin, Mark E. Fornage, Myriam Valdes Hernandez, Maria Wardlaw, Joanna M. Starr, John |
| AuthorAffiliation | From the Centre for Cognitive Ageing and Cognitive Epidemiology (L.M.L., M.V.H., S.M.M., M.E.B., J.S., I.J.D., J.M.W.), Division of Neuroimaging Sciences, Brain Research Imaging Centre, (M.V.H., S.M.M., M.E.B., J.M.W.) and Academic Neuropathology (C.S.), Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, Medical Genetics Section, University of Edinburgh Centre for Genomics and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom (W.D.H., S.E.H., D.J.P.); Department of Bioengineering, Imperial College London, London, United Kingdom (E.B.); BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (M.M., J.M., D.G., A.D.); Department of Biostatistics, Boston University School of Public Health, MA (Q.Y.); The Framingham Heart Study, Boston, MA |
| AuthorAffiliation_xml | – name: From the Centre for Cognitive Ageing and Cognitive Epidemiology (L.M.L., M.V.H., S.M.M., M.E.B., J.S., I.J.D., J.M.W.), Division of Neuroimaging Sciences, Brain Research Imaging Centre, (M.V.H., S.M.M., M.E.B., J.M.W.) and Academic Neuropathology (C.S.), Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, Medical Genetics Section, University of Edinburgh Centre for Genomics and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom (W.D.H., S.E.H., D.J.P.); Department of Bioengineering, Imperial College London, London, United Kingdom (E.B.); BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (M.M., J.M., D.G., A.D.); Department of Biostatistics, Boston University School of Public Health, MA (Q.Y.); The Framingham Heart Study, Boston, MA (Q.Y., S.S.); The Human Genetics Center and Institute of Molecular Medicine, The University of Texas Health Science Center, Houston (M.F.); Departments of Epidemiology, Radiology and Neurology, Erasmus Medical Center, Rotterdam, The Netherlands (M.A.I.); Netherlands Consortium for Healthy Aging, Leiden, The Netherlands (M.A.I.); 12 INSERM U740 (Paris 7 University) and U708 (Bordeaux University), Bordeaux, France (S.D.); Department of Neurology, Lariboisière Hospital, 7 University, DHU Neurovasc Paris Sorbonne, Paris, France (S.D.); University of Versailles Saint-Quentin-en-Yvelines, Versailles, France (S.D.); Department of Neurology, Boston University School of Medicine, MA (S.D., S.S.); Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, MD (L.L.); Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle (J.C.B.); and Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, Austria (R.S.) |
| Author_xml | – sequence: 1 givenname: Lorna surname: Lopez middlename: M. fullname: Lopez, Lorna M. organization: From the Centre for Cognitive Ageing and Cognitive Epidemiology (L.M.L., M.V.H., S.M.M., M.E.B., J.S., I.J.D., J.M.W.), Division of Neuroimaging Sciences, Brain Research Imaging Centre, (M.V.H., S.M.M., M.E.B., J.M.W.) and Academic Neuropathology (C.S.), Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, Medical Genetics Section, University of Edinburgh Centre for Genomics and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom (W.D.H., S.E.H., D.J.P.); Department of Bioengineering, Imperial College London, London, United Kingdom (E.B.); BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (M.M., J.M., D.G., A.D.); Department of Biostatistics, Boston University School of Public Health, MA (Q.Y.); The Framingham Heart Study, Boston, MA (Q.Y., S.S.); The Human Genetics Center and Institute of Molecular Medicine, The University of Texas Health Science Center, Houston (M.F.); Departments of Epidemiology, Radiology and Neurology, Erasmus Medical Center, Rotterdam, The Netherlands (M.A.I.); Netherlands Consortium for Healthy Aging, Leiden, The Netherlands (M.A.I.); 12 INSERM U740 (Paris 7 University) and U708 (Bordeaux University), Bordeaux, France (S.D.); Department of Neurology, Lariboisière Hospital, 7 University, DHU Neurovasc Paris Sorbonne, Paris, France (S.D.); University of Versailles Saint-Quentin-en-Yvelines, Versailles, France (S.D.); Department of Neurology, Boston University School of Medicine, MA (S.D., S.S.); Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, MD (L.L.); Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle (J.C.B.); and Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, Austria (R.S.) – sequence: 2 givenname: W. surname: Hill middlename: David fullname: Hill, W. David – sequence: 3 givenname: Sarah surname: Harris middlename: E. fullname: Harris, Sarah E. – sequence: 4 givenname: Maria surname: Valdes Hernandez fullname: Valdes Hernandez, Maria – sequence: 5 givenname: Susana surname: Munoz Maniega fullname: Munoz Maniega, Susana – sequence: 6 givenname: Mark surname: Bastin middlename: E. fullname: Bastin, Mark E. – sequence: 7 givenname: Emma surname: Bailey fullname: Bailey, Emma – sequence: 8 givenname: Colin surname: Smith fullname: Smith, Colin – sequence: 9 givenname: Martin surname: McBride fullname: McBride, Martin – sequence: 10 givenname: John surname: McClure fullname: McClure, John – sequence: 11 givenname: Delyth surname: Graham fullname: Graham, Delyth – sequence: 12 givenname: Anna surname: Dominiczak fullname: Dominiczak, Anna – sequence: 13 givenname: Qiong surname: Yang fullname: Yang, Qiong – sequence: 14 givenname: Myriam surname: Fornage fullname: Fornage, Myriam – sequence: 15 givenname: M. surname: Ikram middlename: Arfan fullname: Ikram, M. Arfan – sequence: 16 givenname: Stephanie surname: Debette fullname: Debette, Stephanie – sequence: 17 givenname: Lenore surname: Launer fullname: Launer, Lenore – sequence: 18 givenname: Joshua surname: Bis middlename: C. fullname: Bis, Joshua C. – sequence: 19 givenname: Reinhold surname: Schmidt fullname: Schmidt, Reinhold – sequence: 20 givenname: Sudha surname: Seshadri fullname: Seshadri, Sudha – sequence: 21 givenname: David surname: Porteous middlename: J. fullname: Porteous, David J. – sequence: 22 givenname: John surname: Starr fullname: Starr, John – sequence: 23 givenname: Ian surname: Deary middlename: J. fullname: Deary, Ian J. – sequence: 24 givenname: Joanna surname: Wardlaw middlename: M. fullname: Wardlaw, Joanna M. |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25586835$$D View this record in MEDLINE/PubMed |
| BookMark | eNqFUctuEzEUtVARTQt_gNAs2aT4nTELpKhqG0RLJRrE0vJ47hCDYw-2hyp_jyFtBSxgc6-ufB7WOUfoIMQACD0n-IQQSV7drD9cvztbrpb15CcYLyRXj9CMCMrnXNL2AM0wZmpOuVKH6CjnLxhjylrxBB1SIVrZMjFD_QUEyM15itvGNOtkQvamuBiMb5Z17LLLzc00jjGVCriafHGDsSUmVxHvTZkSNHFoPm1cgebKlAKpWe1GSC4UCNkVB_kpejwYn-HZ3T5GH8_P1qer-eX1xdvT5eXcClp_KoBKxoRUtu8YwUSJrjWgeoW7hWyFUcPQU4s7s1iAZKSzLVO9pRwzoJb1C3aM3ux1x6nbQm8hlGS8HpPbmrTT0Tj950twG_05ftecYSkYrwIv7wRS_DZBLnrrsgXvTYA4ZU1kTZdSikWFvvjd68HkPtoKeL0H2BRzTjBo68qvaKu185pg_bNH_dBjPbne91jJ_C_yvf5_aO2edht9LSJ_9dMtJL0B48vm39QfpA21uw |
| CitedBy_id | crossref_primary_10_3389_fphys_2019_01317 crossref_primary_10_1093_ageing_afx097 crossref_primary_10_1212_WNL_0000000000002263 crossref_primary_10_1042_CS20160376 crossref_primary_10_1042_CS20171572 crossref_primary_10_1038_s41537_021_00159_y crossref_primary_10_1155_2022_4280410 crossref_primary_10_1042_CS20171620 crossref_primary_10_2131_jts_44_93 crossref_primary_10_3233_JAD_215053 crossref_primary_10_1161_CIRCGENETICS_116_001664 crossref_primary_10_1007_s11055_024_01587_w crossref_primary_10_1016_j_neurobiolaging_2017_02_014 crossref_primary_10_17116_jnevro202312309158 crossref_primary_10_1177_1934578X221120525 crossref_primary_10_1093_cvr_cvy113 crossref_primary_10_3389_fgene_2019_00615 crossref_primary_10_1016_j_neuroimage_2015_11_057 crossref_primary_10_1177_0284185120932386 crossref_primary_10_1001_jamaneurol_2018_1073 crossref_primary_10_1097_MD_0000000000003857 crossref_primary_10_1016_j_neuroimage_2018_08_075 crossref_primary_10_1016_j_ibneur_2025_01_001 crossref_primary_10_1016_j_jalz_2016_09_006 crossref_primary_10_1007_s00429_017_1414_2 crossref_primary_10_1161_STROKEAHA_115_009627 crossref_primary_10_1161_STROKEAHA_118_020689 crossref_primary_10_1146_annurev_physiol_060821_014521 |
| Cites_doi | 10.1016/j.ajhg.2010.06.009 10.2174/15665240113139990019 10.1111/j.1365-2990.2011.01170.x 10.1016/j.neuroimage.2012.08.002 10.1073/pnas.0506580102 10.1016/j.neuroimage.2010.02.032 10.1086/522374 10.1186/1471-2318-7-28 10.1016/j.neurobiolaging.2013.05.032 10.1212/WNL.0000000000000312 10.1111/j.1747-4949.2011.00659.x 10.1038/tp.2013.114 10.1074/jbc.M110.198523 10.1002/gepi.20533 10.2214/ajr.149.2.351 10.1007/s00330-010-1718-6 10.1136/jnnp.2007.124651 10.1161/STROKEAHA.113.679936 10.1161/STROKEAHA.108.528430 10.1111/j.1365-2990.2010.01147.x 10.1161/STROKEAHA.111.623090 10.1159/000341859 10.1016/j.neurobiolaging.2007.07.015 10.1093/brain/aws012 10.1161/STROKEAHA.109.558809 10.1086/519795 10.1016/S1474-4422(12)70234-X 10.1016/S0140-6736(72)92717-1 10.1111/j.1747-4949.2011.00683.x 10.1007/s00401-010-0652-7 10.1136/bmj.c3666 10.1016/j.cell.2013.06.040 10.1086/498851 10.1002/ana.22403 10.1038/ng.922 10.1136/bmj.316.7139.1236 10.1111/nan.12116 10.1159/000348406 10.1016/S1474-4422(13)70060-7 10.1083/jcb.201205041 10.1016/j.ajhg.2010.02.016 10.1161/STROKEAHA.109.565390 |
| ContentType | Journal Article |
| Copyright | 2015 American Heart Association, Inc. 2015 The Authors. 2015 The Authors. 2015 |
| Copyright_xml | – notice: 2015 American Heart Association, Inc. – notice: 2015 The Authors. – notice: 2015 The Authors. 2015 |
| DBID | AAYXX CITATION CGR CUY CVF ECM EIF NPM 7X8 5PM |
| DOI | 10.1161/STROKEAHA.114.007649 |
| DatabaseName | CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic PubMed Central (Full Participant titles) |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine |
| EISSN | 1524-4628 |
| EndPage | 347 |
| ExternalDocumentID | PMC4306534 25586835 10_1161_STROKEAHA_114_007649 10.1161/STROKEAHA.114.007649 |
| Genre | Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural |
| GrantInformation_xml | – fundername: NHLBI NIH HHS grantid: U01 HL096917 – fundername: NIA NIH HHS grantid: U01 AG049505 – fundername: NIA NIH HHS grantid: AG-023629 – fundername: NINDS NIH HHS grantid: R01 NS017950 – fundername: Biotechnology and Biological Sciences Research Council grantid: BB/C514623/1 – fundername: Intramural NIH HHS grantid: Z01 AG007270 – fundername: NIA NIH HHS grantid: AG033193 – fundername: NIA NIH HHS grantid: R01 AG033193 – fundername: NIA NIH HHS grantid: AG16495 – fundername: NHLBI NIH HHS grantid: R01HL087641 |
| GroupedDBID | --- .3C .55 .GJ .XZ .Z2 01R 0R~ 123 1J1 2WC 3O- 40H 4Q1 4Q2 4Q3 53G 5RE 5VS 6PF 71W 77Y 7O~ A9M AAAAV AAAXR AAGIX AAHPQ AAIQE AAJCS AAMOA AAMTA AAQKA AAQQT AARTV AASCR AASOK AAUEB AAXQO AAYEP AAYJJ ABASU ABBUW ABDIG ABJNI ABPXF ABQRW ABVCZ ABXVJ ABXYN ABZAD ABZZY ACCJW ACDDN ACDOF ACEWG ACGFS ACGOD ACILI ACLDA ACWDW ACWRI ACXJB ACXNZ ACZKN ADBBV ADFPA ADGGA ADHPY ADNKB AE3 AE6 AEBDS AEETU AENEX AFBFQ AFDTB AFEXH AFFNX AFMBP AFNMH AFSOK AFUWQ AGINI AHMBA AHOMT AHQNM AHQVU AHRYX AHVBC AIJEX AINUH AJCLO AJIOK AJNWD AJNYG AJZMW AKCTQ AKULP ALKUP ALMA_UNASSIGNED_HOLDINGS ALMTX AMJPA AMKUR AMNEI AOHHW AOQMC AYCSE BAWUL BCGUY BOYCO BQLVK BS7 C45 CS3 DIK DIWNM DU5 DUNZO E.X E3Z EBS EEVPB EJD ERAAH EX3 F2K F2L F2M F2N F5P FCALG FL- FW0 GNXGY GQDEL GX1 H0~ H13 HLJTE HZ~ IKREB IKYAY IN~ IPNFZ J5H JF9 JG8 JK3 JK8 K8S KD2 KMI KQ8 L-C L7B M18 N4W N9A N~7 N~B N~M O9- OAG OAH OB3 OCUKA ODA ODMTH OGROG OHYEH OK1 OL1 OLG OLH OLU OLV OLY OLZ OPUJH ORVUJ OUVQU OVD OVDNE OVIDH OVLEI OVOZU OWBYB OWU OWV OWW OWX OWY OWZ OXXIT P-K P2P PQQKQ R58 RAH RIG RLZ S4R S4S T8P TEORI TSPGW V2I VVN W3M W8F WH7 WOQ WOW X3V X3W X7M XXN XYM YFH YHZ YQJ YYP ZB8 ZGI ZZMQN AAYXX ADGHP CITATION CGR CUY CVF ECM EIF NPM 7X8 5PM ADSXY |
| ID | FETCH-LOGICAL-c5239-5e2633569cdb310195b8ae9d90b7685a9ffd2c0ba77e631bc839dc2403e2c3d73 |
| ISSN | 0039-2499 1524-4628 |
| IngestDate | Thu Aug 21 18:42:02 EDT 2025 Fri Jul 11 03:49:45 EDT 2025 Mon Jul 21 05:49:15 EDT 2025 Tue Jul 01 03:31:44 EDT 2025 Thu Apr 24 23:12:19 EDT 2025 Fri May 16 03:54:37 EDT 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 2 |
| Keywords | magnetic resonance imaging genetics leukoencephalopathies humans |
| Language | English |
| License | 2015 The Authors. Stroke is published on behalf of the American Heart Association, Inc., by Wolters Kluwer. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited. |
| LinkModel | OpenURL |
| MergedId | FETCHMERGED-LOGICAL-c5239-5e2633569cdb310195b8ae9d90b7685a9ffd2c0ba77e631bc839dc2403e2c3d73 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| OpenAccessLink | https://pubmed.ncbi.nlm.nih.gov/PMC4306534 |
| PMID | 25586835 |
| PQID | 1652422205 |
| PQPubID | 23479 |
| PageCount | 7 |
| ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_4306534 proquest_miscellaneous_1652422205 pubmed_primary_25586835 crossref_citationtrail_10_1161_STROKEAHA_114_007649 crossref_primary_10_1161_STROKEAHA_114_007649 wolterskluwer_health_10_1161_STROKEAHA_114_007649 |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | 2015-February |
| PublicationDateYYYYMMDD | 2015-02-01 |
| PublicationDate_xml | – month: 02 year: 2015 text: 2015-February |
| PublicationDecade | 2010 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | Stroke (1970) |
| PublicationTitleAlternate | Stroke |
| PublicationYear | 2015 |
| Publisher | American Heart Association, Inc Lippincott Williams & Wilkins |
| Publisher_xml | – name: American Heart Association, Inc – name: Lippincott Williams & Wilkins |
| References | e_1_3_4_3_2 e_1_3_4_2_2 e_1_3_4_9_2 e_1_3_4_8_2 e_1_3_4_7_2 e_1_3_4_41_2 e_1_3_4_6_2 e_1_3_4_40_2 e_1_3_4_5_2 e_1_3_4_4_2 e_1_3_4_22_2 e_1_3_4_23_2 e_1_3_4_44_2 e_1_3_4_20_2 e_1_3_4_43_2 e_1_3_4_21_2 e_1_3_4_42_2 e_1_3_4_26_2 e_1_3_4_27_2 e_1_3_4_24_2 e_1_3_4_25_2 e_1_3_4_28_2 e_1_3_4_29_2 e_1_3_4_30_2 e_1_3_4_11_2 e_1_3_4_34_2 e_1_3_4_12_2 e_1_3_4_33_2 e_1_3_4_32_2 e_1_3_4_10_2 e_1_3_4_31_2 Ciemins JJ (e_1_3_4_36_2) 2000; 21 e_1_3_4_15_2 e_1_3_4_38_2 e_1_3_4_16_2 e_1_3_4_37_2 e_1_3_4_13_2 e_1_3_4_14_2 e_1_3_4_35_2 e_1_3_4_19_2 e_1_3_4_17_2 e_1_3_4_18_2 e_1_3_4_39_2 |
| References_xml | – ident: e_1_3_4_24_2 doi: 10.1016/j.ajhg.2010.06.009 – ident: e_1_3_4_41_2 doi: 10.2174/15665240113139990019 – ident: e_1_3_4_14_2 doi: 10.1111/j.1365-2990.2011.01170.x – ident: e_1_3_4_39_2 doi: 10.1016/j.neuroimage.2012.08.002 – ident: e_1_3_4_27_2 doi: 10.1073/pnas.0506580102 – ident: e_1_3_4_32_2 doi: 10.1016/j.neuroimage.2010.02.032 – ident: e_1_3_4_28_2 doi: 10.1086/522374 – ident: e_1_3_4_17_2 doi: 10.1186/1471-2318-7-28 – ident: e_1_3_4_43_2 doi: 10.1016/j.neurobiolaging.2013.05.032 – ident: e_1_3_4_4_2 doi: 10.1212/WNL.0000000000000312 – ident: e_1_3_4_13_2 doi: 10.1111/j.1747-4949.2011.00659.x – ident: e_1_3_4_26_2 doi: 10.1038/tp.2013.114 – ident: e_1_3_4_34_2 doi: 10.1074/jbc.M110.198523 – ident: e_1_3_4_29_2 doi: 10.1002/gepi.20533 – ident: e_1_3_4_19_2 doi: 10.2214/ajr.149.2.351 – volume: 21 start-page: 1483 year: 2000 ident: e_1_3_4_36_2 article-title: Abnormal white matter signal in ataxia telangiectasia. publication-title: AJNR Am J Neuroradiol – ident: e_1_3_4_20_2 doi: 10.1007/s00330-010-1718-6 – ident: e_1_3_4_42_2 doi: 10.1136/jnnp.2007.124651 – ident: e_1_3_4_11_2 doi: 10.1161/STROKEAHA.113.679936 – ident: e_1_3_4_12_2 doi: 10.1161/STROKEAHA.108.528430 – ident: e_1_3_4_6_2 doi: 10.1111/j.1365-2990.2010.01147.x – ident: e_1_3_4_9_2 doi: 10.1161/STROKEAHA.111.623090 – ident: e_1_3_4_21_2 doi: 10.1159/000341859 – ident: e_1_3_4_38_2 doi: 10.1016/j.neurobiolaging.2007.07.015 – ident: e_1_3_4_44_2 doi: 10.1093/brain/aws012 – ident: e_1_3_4_7_2 doi: 10.1161/STROKEAHA.109.558809 – ident: e_1_3_4_25_2 doi: 10.1086/519795 – ident: e_1_3_4_10_2 doi: 10.1016/S1474-4422(12)70234-X – ident: e_1_3_4_35_2 doi: 10.1016/S0140-6736(72)92717-1 – ident: e_1_3_4_18_2 doi: 10.1111/j.1747-4949.2011.00683.x – ident: e_1_3_4_37_2 doi: 10.1007/s00401-010-0652-7 – ident: e_1_3_4_2_2 doi: 10.1136/bmj.c3666 – ident: e_1_3_4_16_2 doi: 10.1016/j.cell.2013.06.040 – ident: e_1_3_4_31_2 doi: 10.1086/498851 – ident: e_1_3_4_8_2 doi: 10.1002/ana.22403 – ident: e_1_3_4_23_2 doi: 10.1038/ng.922 – ident: e_1_3_4_30_2 doi: 10.1136/bmj.316.7139.1236 – ident: e_1_3_4_15_2 doi: 10.1111/nan.12116 – ident: e_1_3_4_40_2 doi: 10.1159/000348406 – ident: e_1_3_4_3_2 doi: 10.1016/S1474-4422(13)70060-7 – ident: e_1_3_4_33_2 doi: 10.1083/jcb.201205041 – ident: e_1_3_4_22_2 doi: 10.1016/j.ajhg.2010.02.016 – ident: e_1_3_4_5_2 doi: 10.1161/STROKEAHA.109.565390 |
| SSID | ssj0002385 |
| Score | 2.3110142 |
| Snippet | BACKGROUND AND PURPOSE—White matter hyperintensities (WMH) of presumed vascular origin increase the risk of stroke and dementia. Despite strong WMH... White matter hyperintensities (WMH) of presumed vascular origin increase the risk of stroke and dementia. Despite strong WMH heritability, few gene... Supplemental Digital Content is available in the text. |
| SourceID | pubmedcentral proquest pubmed crossref wolterskluwer |
| SourceType | Open Access Repository Aggregation Database Index Database Enrichment Source Publisher |
| StartPage | 341 |
| SubjectTerms | Aged Alzheimer Disease - diagnosis Alzheimer Disease - epidemiology Alzheimer Disease - genetics Animals Brain - pathology Causality Dementia - diagnosis Dementia - epidemiology Dementia - genetics Female Genome-Wide Association Study - methods Humans Leukoencephalopathies - diagnosis Leukoencephalopathies - epidemiology Leukoencephalopathies - genetics Male Original Contributions Polymorphism, Single Nucleotide - genetics Rats Rats, Inbred SHR Rats, Wistar Risk Factors Translational Research, Biomedical - methods White Matter - pathology |
| Title | Genes From a Translational Analysis Support a Multifactorial Nature of White Matter Hyperintensities |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/25586835 https://www.proquest.com/docview/1652422205 https://pubmed.ncbi.nlm.nih.gov/PMC4306534 |
| Volume | 46 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1tb9MwELZgSAgJId4JbzIS36ZAYztu_bFCQxVbQbAO9i1KHEeb1iVVm2qCX8-d7aTJOl6_RFHiOmmfp5e7y91jQl4LZaQSLA95WmShiIQJM4jZQtjBB6weCI2pgelHOTkSH47j400yx3aX1Nkb_ePKvpL_QRWOAa7YJfsPyLaTwgHYB3xhCwjD9q8wRs3olesQSXGxh3I1b3J7aSM2slov0MWGAbZ20K2vg2lyJ-mJzuIFvkrYPbdKm7sn31H72BW2102FofdeD-tldWad0kgNB50kwkG1cJnoA1zwuJNh9WLZ37q182julkunbWAT0ptuiK_pPIdvNOkmt6epq4RukxNR3NQz47PFG1QmQux_7Vpcn3Q87QS-znxyJ4K1bdYlmvXD2ZdP-3vjyRgFjlHzXDq10w7Si3MLNcRJIzlyOiiX5LSbU9fJDQaRBdry_c8bgXnwYGLfYQkXfXvVJVE_2k_Sd2a2IpTtQtvbFxUWQazObA9Ex5OZ3SV3fAhCx45P98g1U94nN6e-yOIByS2tKNKKprRHK9rQinpawYA-raijFa0KamlFHa3oZVo9JEfv92bvJqFfjCPUMeMqjA2TnMdS6TyDkCBScTZKjcrVIIOINU5VUeRMD7J0ODSSR5kGzzvXqPZomOb5kD8iO2VVmieEMmwPU4XOYwj-RVSMjFFMapSoLRgXLCC8-VUT7ZXqccGUeWIjVhklLSzYVJ84WAIStp9aOKWWP4x_1QCWgEnF92Rpaar1KokkkJZhB3pAHjsA2xkb5AMy7EHbDkC59v6Z8vTEyrYLjjrQIiBRjwSJa3j-7b0-_eV9PCO3Nv-752SnXq7NC3CT6-ylJfZPxjO82g |
| linkProvider | Colorado Alliance of Research Libraries |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Genes+from+a+translational+analysis+support+a+multifactorial+nature+of+white+matter+hyperintensities&rft.jtitle=Stroke+%281970%29&rft.au=Lopez%2C+Lorna+M&rft.au=Hill%2C+W+David&rft.au=Harris%2C+Sarah+E&rft.au=Valdes+Hernandez%2C+Maria&rft.date=2015-02-01&rft.eissn=1524-4628&rft.volume=46&rft.issue=2&rft.spage=341&rft_id=info:doi/10.1161%2FSTROKEAHA.114.007649&rft_id=info%3Apmid%2F25586835&rft.externalDocID=25586835 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0039-2499&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0039-2499&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0039-2499&client=summon |