Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting
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...
Gespeichert in:
| Veröffentlicht in: | NEUROLOGY 2019-01, Vol.92 (5), p.E486-E503 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | E503 |
|---|---|
| container_issue | 5 |
| container_start_page | E486 |
| container_title | NEUROLOGY |
| container_volume | 92 |
| creator | Chauhan, Ganesh Adams, Hieab H.H Satizabal, Claudia L Bis, Joshua C Teumer, Alexander Sargurupremraj, Muralidharan Hofer, Edith Trompet, Stella Hilal, Saima Smith, Albert Vernon Jian, Xueqiu Malik, Rainer Traylor, Matthew Pulit, Sara L Amouyel, Philippe Mazoyer, Bernard Zhu, Yi-Cheng Kaffashian, Sara Schilling, Sabrina Beecham, Gary W Montine, Thomas J Schellenberg, Gerard D Kjartansson, Olafur Gudnason, Vilmundur Knopman, David S Griswold, Michael E Windham, B. Gwen Gottesman, Rebecca F Mosley, Thomas H Schmidt, Reinhold Saba, Yasaman Schmidt, Helena Takeuchi, Fumihiko Yamaguchi, Shuhei Nabika, Toru Kato, Norihiro Rajan, Kumar B Aggarwal, Neelum T De Jager, Philip L Evans, Denis A Psaty, Bruce M Rotter, Jerome I Rice, Kenneth Lopez, Oscar L Liao, Jiemin Chen, Christopher Cheng, Ching-Yu Wong, Tien Y Ikram, Mohammad K van der Lee, Sven J Amin, Najaf Chouraki, Vincent DeStefano, Anita L Aparicio, Hugo J Romero, Jose R Maillard, Pauline DeCarli, Charles Wardlaw, Joanna M Hernandez, Maria del C. Valdes Luciano, Michelle Liewald, David Deary, Ian J Starr, John M Bastin, Mark E Maniega, Susana Munoz Slagboom, P. Eline Beekman, Marian Deelen, Joris Uh, Hae-Won Lemmens, Robin Brodaty, Henry Wright, Margaret J Ames, David Boncoraglio, Giorgio B Hopewell, Jemma C Beecham, Ashley H Blanton, Susan H Wright, Clinton B Sacco, Ralph L Wen, Wei Thalamuthu, Anbupalam Armstrong, Nicola J Chong, Elizabeth Schofield, Peter R Kwok, John B van der Grond, Jeroen Stott, David J Ford, Ian Jukema, J. Wouter Vernooij, Meike W Hofman, Albert Uitterlinden, Andre G van der Lugt, Aad Wittfeld, Katharina Grabe, Hans J Hosten, Norbert von Sarnowski, Bettina Voelker, Uwe Levi, Christopher Jimenez-Conde, Jordi |
| description | 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. |
| format | Article |
| fullrecord | <record><control><sourceid>kuleuven</sourceid><recordid>TN_cdi_kuleuven_dspace_123456789_634974</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>123456789_634974</sourcerecordid><originalsourceid>FETCH-kuleuven_dspace_123456789_6349743</originalsourceid><addsrcrecordid>eNqNjDGOwjAQAF1wEjngD9tRoEghDiSpERxXXHOit5ZkjUwsJ_JuEPweCh5ANVOMZqKSLMurVFdlNVXfzNcsW2_ysk6U-aFA4hrA0IJ3llgeniA67sBiI31ksH2Ev__ftCXrArVwjugCuGAxNsIvAYShH0aP4vqQnpFfEZOIC5e5-rLomRZvztTysD_tjmk3ehpvFEzLAzZk1rkuNtuyqs1WF3VZ6JlafVYauYv-_PsEsAtSew</addsrcrecordid><sourcetype>Institutional Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting</title><source>Journals@Ovid Ovid Autoload</source><source>Lirias (KU Leuven Association)</source><source>Alma/SFX Local Collection</source><creator>Chauhan, Ganesh ; Adams, Hieab H.H ; Satizabal, Claudia L ; Bis, Joshua C ; Teumer, Alexander ; Sargurupremraj, Muralidharan ; Hofer, Edith ; Trompet, Stella ; Hilal, Saima ; Smith, Albert Vernon ; Jian, Xueqiu ; Malik, Rainer ; Traylor, Matthew ; Pulit, Sara L ; Amouyel, Philippe ; Mazoyer, Bernard ; Zhu, Yi-Cheng ; Kaffashian, Sara ; Schilling, Sabrina ; Beecham, Gary W ; Montine, Thomas J ; Schellenberg, Gerard D ; Kjartansson, Olafur ; Gudnason, Vilmundur ; Knopman, David S ; Griswold, Michael E ; Windham, B. Gwen ; Gottesman, Rebecca F ; Mosley, Thomas H ; Schmidt, Reinhold ; Saba, Yasaman ; Schmidt, Helena ; Takeuchi, Fumihiko ; Yamaguchi, Shuhei ; Nabika, Toru ; Kato, Norihiro ; Rajan, Kumar B ; Aggarwal, Neelum T ; De Jager, Philip L ; Evans, Denis A ; Psaty, Bruce M ; Rotter, Jerome I ; Rice, Kenneth ; Lopez, Oscar L ; Liao, Jiemin ; Chen, Christopher ; Cheng, Ching-Yu ; Wong, Tien Y ; Ikram, Mohammad K ; van der Lee, Sven J ; Amin, Najaf ; Chouraki, Vincent ; DeStefano, Anita L ; Aparicio, Hugo J ; Romero, Jose R ; Maillard, Pauline ; DeCarli, Charles ; Wardlaw, Joanna M ; Hernandez, Maria del C. Valdes ; Luciano, Michelle ; Liewald, David ; Deary, Ian J ; Starr, John M ; Bastin, Mark E ; Maniega, Susana Munoz ; Slagboom, P. Eline ; Beekman, Marian ; Deelen, Joris ; Uh, Hae-Won ; Lemmens, Robin ; Brodaty, Henry ; Wright, Margaret J ; Ames, David ; Boncoraglio, Giorgio B ; Hopewell, Jemma C ; Beecham, Ashley H ; Blanton, Susan H ; Wright, Clinton B ; Sacco, Ralph L ; Wen, Wei ; Thalamuthu, Anbupalam ; Armstrong, Nicola J ; Chong, Elizabeth ; Schofield, Peter R ; Kwok, John B ; van der Grond, Jeroen ; Stott, David J ; Ford, Ian ; Jukema, J. Wouter ; Vernooij, Meike W ; Hofman, Albert ; Uitterlinden, Andre G ; van der Lugt, Aad ; Wittfeld, Katharina ; Grabe, Hans J ; Hosten, Norbert ; von Sarnowski, Bettina ; Voelker, Uwe ; Levi, Christopher ; Jimenez-Conde, Jordi</creator><creatorcontrib>Chauhan, Ganesh ; Adams, Hieab H.H ; Satizabal, Claudia L ; Bis, Joshua C ; Teumer, Alexander ; Sargurupremraj, Muralidharan ; Hofer, Edith ; Trompet, Stella ; Hilal, Saima ; Smith, Albert Vernon ; Jian, Xueqiu ; Malik, Rainer ; Traylor, Matthew ; Pulit, Sara L ; Amouyel, Philippe ; Mazoyer, Bernard ; Zhu, Yi-Cheng ; Kaffashian, Sara ; Schilling, Sabrina ; Beecham, Gary W ; Montine, Thomas J ; Schellenberg, Gerard D ; Kjartansson, Olafur ; Gudnason, Vilmundur ; Knopman, David S ; Griswold, Michael E ; Windham, B. Gwen ; Gottesman, Rebecca F ; Mosley, Thomas H ; Schmidt, Reinhold ; Saba, Yasaman ; Schmidt, Helena ; Takeuchi, Fumihiko ; Yamaguchi, Shuhei ; Nabika, Toru ; Kato, Norihiro ; Rajan, Kumar B ; Aggarwal, Neelum T ; De Jager, Philip L ; Evans, Denis A ; Psaty, Bruce M ; Rotter, Jerome I ; Rice, Kenneth ; Lopez, Oscar L ; Liao, Jiemin ; Chen, Christopher ; Cheng, Ching-Yu ; Wong, Tien Y ; Ikram, Mohammad K ; van der Lee, Sven J ; Amin, Najaf ; Chouraki, Vincent ; DeStefano, Anita L ; Aparicio, Hugo J ; Romero, Jose R ; Maillard, Pauline ; DeCarli, Charles ; Wardlaw, Joanna M ; Hernandez, Maria del C. Valdes ; Luciano, Michelle ; Liewald, David ; Deary, Ian J ; Starr, John M ; Bastin, Mark E ; Maniega, Susana Munoz ; Slagboom, P. Eline ; Beekman, Marian ; Deelen, Joris ; Uh, Hae-Won ; Lemmens, Robin ; Brodaty, Henry ; Wright, Margaret J ; Ames, David ; Boncoraglio, Giorgio B ; Hopewell, Jemma C ; Beecham, Ashley H ; Blanton, Susan H ; Wright, Clinton B ; Sacco, Ralph L ; Wen, Wei ; Thalamuthu, Anbupalam ; Armstrong, Nicola J ; Chong, Elizabeth ; Schofield, Peter R ; Kwok, John B ; van der Grond, Jeroen ; Stott, David J ; Ford, Ian ; Jukema, J. Wouter ; Vernooij, Meike W ; Hofman, Albert ; Uitterlinden, Andre G ; van der Lugt, Aad ; Wittfeld, Katharina ; Grabe, Hans J ; Hosten, Norbert ; von Sarnowski, Bettina ; Voelker, Uwe ; Levi, Christopher ; Jimenez-Conde, Jordi</creatorcontrib><description>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.</description><identifier>ISSN: 0028-3878</identifier><language>eng</language><publisher>LIPPINCOTT WILLIAMS & WILKINS</publisher><ispartof>NEUROLOGY, 2019-01, Vol.92 (5), p.E486-E503</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,315,776,780,27837</link.rule.ids></links><search><creatorcontrib>Chauhan, Ganesh</creatorcontrib><creatorcontrib>Adams, Hieab H.H</creatorcontrib><creatorcontrib>Satizabal, Claudia L</creatorcontrib><creatorcontrib>Bis, Joshua C</creatorcontrib><creatorcontrib>Teumer, Alexander</creatorcontrib><creatorcontrib>Sargurupremraj, Muralidharan</creatorcontrib><creatorcontrib>Hofer, Edith</creatorcontrib><creatorcontrib>Trompet, Stella</creatorcontrib><creatorcontrib>Hilal, Saima</creatorcontrib><creatorcontrib>Smith, Albert Vernon</creatorcontrib><creatorcontrib>Jian, Xueqiu</creatorcontrib><creatorcontrib>Malik, Rainer</creatorcontrib><creatorcontrib>Traylor, Matthew</creatorcontrib><creatorcontrib>Pulit, Sara L</creatorcontrib><creatorcontrib>Amouyel, Philippe</creatorcontrib><creatorcontrib>Mazoyer, Bernard</creatorcontrib><creatorcontrib>Zhu, Yi-Cheng</creatorcontrib><creatorcontrib>Kaffashian, Sara</creatorcontrib><creatorcontrib>Schilling, Sabrina</creatorcontrib><creatorcontrib>Beecham, Gary W</creatorcontrib><creatorcontrib>Montine, Thomas J</creatorcontrib><creatorcontrib>Schellenberg, Gerard D</creatorcontrib><creatorcontrib>Kjartansson, Olafur</creatorcontrib><creatorcontrib>Gudnason, Vilmundur</creatorcontrib><creatorcontrib>Knopman, David S</creatorcontrib><creatorcontrib>Griswold, Michael E</creatorcontrib><creatorcontrib>Windham, B. Gwen</creatorcontrib><creatorcontrib>Gottesman, Rebecca F</creatorcontrib><creatorcontrib>Mosley, Thomas H</creatorcontrib><creatorcontrib>Schmidt, Reinhold</creatorcontrib><creatorcontrib>Saba, Yasaman</creatorcontrib><creatorcontrib>Schmidt, Helena</creatorcontrib><creatorcontrib>Takeuchi, Fumihiko</creatorcontrib><creatorcontrib>Yamaguchi, Shuhei</creatorcontrib><creatorcontrib>Nabika, Toru</creatorcontrib><creatorcontrib>Kato, Norihiro</creatorcontrib><creatorcontrib>Rajan, Kumar B</creatorcontrib><creatorcontrib>Aggarwal, Neelum T</creatorcontrib><creatorcontrib>De Jager, Philip L</creatorcontrib><creatorcontrib>Evans, Denis A</creatorcontrib><creatorcontrib>Psaty, Bruce M</creatorcontrib><creatorcontrib>Rotter, Jerome I</creatorcontrib><creatorcontrib>Rice, Kenneth</creatorcontrib><creatorcontrib>Lopez, Oscar L</creatorcontrib><creatorcontrib>Liao, Jiemin</creatorcontrib><creatorcontrib>Chen, Christopher</creatorcontrib><creatorcontrib>Cheng, Ching-Yu</creatorcontrib><creatorcontrib>Wong, Tien Y</creatorcontrib><creatorcontrib>Ikram, Mohammad K</creatorcontrib><creatorcontrib>van der Lee, Sven J</creatorcontrib><creatorcontrib>Amin, Najaf</creatorcontrib><creatorcontrib>Chouraki, Vincent</creatorcontrib><creatorcontrib>DeStefano, Anita L</creatorcontrib><creatorcontrib>Aparicio, Hugo J</creatorcontrib><creatorcontrib>Romero, Jose R</creatorcontrib><creatorcontrib>Maillard, Pauline</creatorcontrib><creatorcontrib>DeCarli, Charles</creatorcontrib><creatorcontrib>Wardlaw, Joanna M</creatorcontrib><creatorcontrib>Hernandez, Maria del C. Valdes</creatorcontrib><creatorcontrib>Luciano, Michelle</creatorcontrib><creatorcontrib>Liewald, David</creatorcontrib><creatorcontrib>Deary, Ian J</creatorcontrib><creatorcontrib>Starr, John M</creatorcontrib><creatorcontrib>Bastin, Mark E</creatorcontrib><creatorcontrib>Maniega, Susana Munoz</creatorcontrib><creatorcontrib>Slagboom, P. Eline</creatorcontrib><creatorcontrib>Beekman, Marian</creatorcontrib><creatorcontrib>Deelen, Joris</creatorcontrib><creatorcontrib>Uh, Hae-Won</creatorcontrib><creatorcontrib>Lemmens, Robin</creatorcontrib><creatorcontrib>Brodaty, Henry</creatorcontrib><creatorcontrib>Wright, Margaret J</creatorcontrib><creatorcontrib>Ames, David</creatorcontrib><creatorcontrib>Boncoraglio, Giorgio B</creatorcontrib><creatorcontrib>Hopewell, Jemma C</creatorcontrib><creatorcontrib>Beecham, Ashley H</creatorcontrib><creatorcontrib>Blanton, Susan H</creatorcontrib><creatorcontrib>Wright, Clinton B</creatorcontrib><creatorcontrib>Sacco, Ralph L</creatorcontrib><creatorcontrib>Wen, Wei</creatorcontrib><creatorcontrib>Thalamuthu, Anbupalam</creatorcontrib><creatorcontrib>Armstrong, Nicola J</creatorcontrib><creatorcontrib>Chong, Elizabeth</creatorcontrib><creatorcontrib>Schofield, Peter R</creatorcontrib><creatorcontrib>Kwok, John B</creatorcontrib><creatorcontrib>van der Grond, Jeroen</creatorcontrib><creatorcontrib>Stott, David J</creatorcontrib><creatorcontrib>Ford, Ian</creatorcontrib><creatorcontrib>Jukema, J. Wouter</creatorcontrib><creatorcontrib>Vernooij, Meike W</creatorcontrib><creatorcontrib>Hofman, Albert</creatorcontrib><creatorcontrib>Uitterlinden, Andre G</creatorcontrib><creatorcontrib>van der Lugt, Aad</creatorcontrib><creatorcontrib>Wittfeld, Katharina</creatorcontrib><creatorcontrib>Grabe, Hans J</creatorcontrib><creatorcontrib>Hosten, Norbert</creatorcontrib><creatorcontrib>von Sarnowski, Bettina</creatorcontrib><creatorcontrib>Voelker, Uwe</creatorcontrib><creatorcontrib>Levi, Christopher</creatorcontrib><creatorcontrib>Jimenez-Conde, Jordi</creatorcontrib><title>Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting</title><title>NEUROLOGY</title><description>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.</description><issn>0028-3878</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>FZOIL</sourceid><recordid>eNqNjDGOwjAQAF1wEjngD9tRoEghDiSpERxXXHOit5ZkjUwsJ_JuEPweCh5ANVOMZqKSLMurVFdlNVXfzNcsW2_ysk6U-aFA4hrA0IJ3llgeniA67sBiI31ksH2Ev__ftCXrArVwjugCuGAxNsIvAYShH0aP4vqQnpFfEZOIC5e5-rLomRZvztTysD_tjmk3ehpvFEzLAzZk1rkuNtuyqs1WF3VZ6JlafVYauYv-_PsEsAtSew</recordid><startdate>20190129</startdate><enddate>20190129</enddate><creator>Chauhan, Ganesh</creator><creator>Adams, Hieab H.H</creator><creator>Satizabal, Claudia L</creator><creator>Bis, Joshua C</creator><creator>Teumer, Alexander</creator><creator>Sargurupremraj, Muralidharan</creator><creator>Hofer, Edith</creator><creator>Trompet, Stella</creator><creator>Hilal, Saima</creator><creator>Smith, Albert Vernon</creator><creator>Jian, Xueqiu</creator><creator>Malik, Rainer</creator><creator>Traylor, Matthew</creator><creator>Pulit, Sara L</creator><creator>Amouyel, Philippe</creator><creator>Mazoyer, Bernard</creator><creator>Zhu, Yi-Cheng</creator><creator>Kaffashian, Sara</creator><creator>Schilling, Sabrina</creator><creator>Beecham, Gary W</creator><creator>Montine, Thomas J</creator><creator>Schellenberg, Gerard D</creator><creator>Kjartansson, Olafur</creator><creator>Gudnason, Vilmundur</creator><creator>Knopman, David S</creator><creator>Griswold, Michael E</creator><creator>Windham, B. Gwen</creator><creator>Gottesman, Rebecca F</creator><creator>Mosley, Thomas H</creator><creator>Schmidt, Reinhold</creator><creator>Saba, Yasaman</creator><creator>Schmidt, Helena</creator><creator>Takeuchi, Fumihiko</creator><creator>Yamaguchi, Shuhei</creator><creator>Nabika, Toru</creator><creator>Kato, Norihiro</creator><creator>Rajan, Kumar B</creator><creator>Aggarwal, Neelum T</creator><creator>De Jager, Philip L</creator><creator>Evans, Denis A</creator><creator>Psaty, Bruce M</creator><creator>Rotter, Jerome I</creator><creator>Rice, Kenneth</creator><creator>Lopez, Oscar L</creator><creator>Liao, Jiemin</creator><creator>Chen, Christopher</creator><creator>Cheng, Ching-Yu</creator><creator>Wong, Tien Y</creator><creator>Ikram, Mohammad K</creator><creator>van der Lee, Sven J</creator><creator>Amin, Najaf</creator><creator>Chouraki, Vincent</creator><creator>DeStefano, Anita L</creator><creator>Aparicio, Hugo J</creator><creator>Romero, Jose R</creator><creator>Maillard, Pauline</creator><creator>DeCarli, Charles</creator><creator>Wardlaw, Joanna M</creator><creator>Hernandez, Maria del C. Valdes</creator><creator>Luciano, Michelle</creator><creator>Liewald, David</creator><creator>Deary, Ian J</creator><creator>Starr, John M</creator><creator>Bastin, Mark E</creator><creator>Maniega, Susana Munoz</creator><creator>Slagboom, P. Eline</creator><creator>Beekman, Marian</creator><creator>Deelen, Joris</creator><creator>Uh, Hae-Won</creator><creator>Lemmens, Robin</creator><creator>Brodaty, Henry</creator><creator>Wright, Margaret J</creator><creator>Ames, David</creator><creator>Boncoraglio, Giorgio B</creator><creator>Hopewell, Jemma C</creator><creator>Beecham, Ashley H</creator><creator>Blanton, Susan H</creator><creator>Wright, Clinton B</creator><creator>Sacco, Ralph L</creator><creator>Wen, Wei</creator><creator>Thalamuthu, Anbupalam</creator><creator>Armstrong, Nicola J</creator><creator>Chong, Elizabeth</creator><creator>Schofield, Peter R</creator><creator>Kwok, John B</creator><creator>van der Grond, Jeroen</creator><creator>Stott, David J</creator><creator>Ford, Ian</creator><creator>Jukema, J. Wouter</creator><creator>Vernooij, Meike W</creator><creator>Hofman, Albert</creator><creator>Uitterlinden, Andre G</creator><creator>van der Lugt, Aad</creator><creator>Wittfeld, Katharina</creator><creator>Grabe, Hans J</creator><creator>Hosten, Norbert</creator><creator>von Sarnowski, Bettina</creator><creator>Voelker, Uwe</creator><creator>Levi, Christopher</creator><creator>Jimenez-Conde, Jordi</creator><general>LIPPINCOTT WILLIAMS & WILKINS</general><scope>FZOIL</scope></search><sort><creationdate>20190129</creationdate><title>Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting</title><author>Chauhan, Ganesh ; Adams, Hieab H.H ; Satizabal, Claudia L ; Bis, Joshua C ; Teumer, Alexander ; Sargurupremraj, Muralidharan ; Hofer, Edith ; Trompet, Stella ; Hilal, Saima ; Smith, Albert Vernon ; Jian, Xueqiu ; Malik, Rainer ; Traylor, Matthew ; Pulit, Sara L ; Amouyel, Philippe ; Mazoyer, Bernard ; Zhu, Yi-Cheng ; Kaffashian, Sara ; Schilling, Sabrina ; Beecham, Gary W ; Montine, Thomas J ; Schellenberg, Gerard D ; Kjartansson, Olafur ; Gudnason, Vilmundur ; Knopman, David S ; Griswold, Michael E ; Windham, B. Gwen ; Gottesman, Rebecca F ; Mosley, Thomas H ; Schmidt, Reinhold ; Saba, Yasaman ; Schmidt, Helena ; Takeuchi, Fumihiko ; Yamaguchi, Shuhei ; Nabika, Toru ; Kato, Norihiro ; Rajan, Kumar B ; Aggarwal, Neelum T ; De Jager, Philip L ; Evans, Denis A ; Psaty, Bruce M ; Rotter, Jerome I ; Rice, Kenneth ; Lopez, Oscar L ; Liao, Jiemin ; Chen, Christopher ; Cheng, Ching-Yu ; Wong, Tien Y ; Ikram, Mohammad K ; van der Lee, Sven J ; Amin, Najaf ; Chouraki, Vincent ; DeStefano, Anita L ; Aparicio, Hugo J ; Romero, Jose R ; Maillard, Pauline ; DeCarli, Charles ; Wardlaw, Joanna M ; Hernandez, Maria del C. Valdes ; Luciano, Michelle ; Liewald, David ; Deary, Ian J ; Starr, John M ; Bastin, Mark E ; Maniega, Susana Munoz ; Slagboom, P. Eline ; Beekman, Marian ; Deelen, Joris ; Uh, Hae-Won ; Lemmens, Robin ; Brodaty, Henry ; Wright, Margaret J ; Ames, David ; Boncoraglio, Giorgio B ; Hopewell, Jemma C ; Beecham, Ashley H ; Blanton, Susan H ; Wright, Clinton B ; Sacco, Ralph L ; Wen, Wei ; Thalamuthu, Anbupalam ; Armstrong, Nicola J ; Chong, Elizabeth ; Schofield, Peter R ; Kwok, John B ; van der Grond, Jeroen ; Stott, David J ; Ford, Ian ; Jukema, J. Wouter ; Vernooij, Meike W ; Hofman, Albert ; Uitterlinden, Andre G ; van der Lugt, Aad ; Wittfeld, Katharina ; Grabe, Hans J ; Hosten, Norbert ; von Sarnowski, Bettina ; Voelker, Uwe ; Levi, Christopher ; Jimenez-Conde, Jordi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-kuleuven_dspace_123456789_6349743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chauhan, Ganesh</creatorcontrib><creatorcontrib>Adams, Hieab H.H</creatorcontrib><creatorcontrib>Satizabal, Claudia L</creatorcontrib><creatorcontrib>Bis, Joshua C</creatorcontrib><creatorcontrib>Teumer, Alexander</creatorcontrib><creatorcontrib>Sargurupremraj, Muralidharan</creatorcontrib><creatorcontrib>Hofer, Edith</creatorcontrib><creatorcontrib>Trompet, Stella</creatorcontrib><creatorcontrib>Hilal, Saima</creatorcontrib><creatorcontrib>Smith, Albert Vernon</creatorcontrib><creatorcontrib>Jian, Xueqiu</creatorcontrib><creatorcontrib>Malik, Rainer</creatorcontrib><creatorcontrib>Traylor, Matthew</creatorcontrib><creatorcontrib>Pulit, Sara L</creatorcontrib><creatorcontrib>Amouyel, Philippe</creatorcontrib><creatorcontrib>Mazoyer, Bernard</creatorcontrib><creatorcontrib>Zhu, Yi-Cheng</creatorcontrib><creatorcontrib>Kaffashian, Sara</creatorcontrib><creatorcontrib>Schilling, Sabrina</creatorcontrib><creatorcontrib>Beecham, Gary W</creatorcontrib><creatorcontrib>Montine, Thomas J</creatorcontrib><creatorcontrib>Schellenberg, Gerard D</creatorcontrib><creatorcontrib>Kjartansson, Olafur</creatorcontrib><creatorcontrib>Gudnason, Vilmundur</creatorcontrib><creatorcontrib>Knopman, David S</creatorcontrib><creatorcontrib>Griswold, Michael E</creatorcontrib><creatorcontrib>Windham, B. Gwen</creatorcontrib><creatorcontrib>Gottesman, Rebecca F</creatorcontrib><creatorcontrib>Mosley, Thomas H</creatorcontrib><creatorcontrib>Schmidt, Reinhold</creatorcontrib><creatorcontrib>Saba, Yasaman</creatorcontrib><creatorcontrib>Schmidt, Helena</creatorcontrib><creatorcontrib>Takeuchi, Fumihiko</creatorcontrib><creatorcontrib>Yamaguchi, Shuhei</creatorcontrib><creatorcontrib>Nabika, Toru</creatorcontrib><creatorcontrib>Kato, Norihiro</creatorcontrib><creatorcontrib>Rajan, Kumar B</creatorcontrib><creatorcontrib>Aggarwal, Neelum T</creatorcontrib><creatorcontrib>De Jager, Philip L</creatorcontrib><creatorcontrib>Evans, Denis A</creatorcontrib><creatorcontrib>Psaty, Bruce M</creatorcontrib><creatorcontrib>Rotter, Jerome I</creatorcontrib><creatorcontrib>Rice, Kenneth</creatorcontrib><creatorcontrib>Lopez, Oscar L</creatorcontrib><creatorcontrib>Liao, Jiemin</creatorcontrib><creatorcontrib>Chen, Christopher</creatorcontrib><creatorcontrib>Cheng, Ching-Yu</creatorcontrib><creatorcontrib>Wong, Tien Y</creatorcontrib><creatorcontrib>Ikram, Mohammad K</creatorcontrib><creatorcontrib>van der Lee, Sven J</creatorcontrib><creatorcontrib>Amin, Najaf</creatorcontrib><creatorcontrib>Chouraki, Vincent</creatorcontrib><creatorcontrib>DeStefano, Anita L</creatorcontrib><creatorcontrib>Aparicio, Hugo J</creatorcontrib><creatorcontrib>Romero, Jose R</creatorcontrib><creatorcontrib>Maillard, Pauline</creatorcontrib><creatorcontrib>DeCarli, Charles</creatorcontrib><creatorcontrib>Wardlaw, Joanna M</creatorcontrib><creatorcontrib>Hernandez, Maria del C. Valdes</creatorcontrib><creatorcontrib>Luciano, Michelle</creatorcontrib><creatorcontrib>Liewald, David</creatorcontrib><creatorcontrib>Deary, Ian J</creatorcontrib><creatorcontrib>Starr, John M</creatorcontrib><creatorcontrib>Bastin, Mark E</creatorcontrib><creatorcontrib>Maniega, Susana Munoz</creatorcontrib><creatorcontrib>Slagboom, P. Eline</creatorcontrib><creatorcontrib>Beekman, Marian</creatorcontrib><creatorcontrib>Deelen, Joris</creatorcontrib><creatorcontrib>Uh, Hae-Won</creatorcontrib><creatorcontrib>Lemmens, Robin</creatorcontrib><creatorcontrib>Brodaty, Henry</creatorcontrib><creatorcontrib>Wright, Margaret J</creatorcontrib><creatorcontrib>Ames, David</creatorcontrib><creatorcontrib>Boncoraglio, Giorgio B</creatorcontrib><creatorcontrib>Hopewell, Jemma C</creatorcontrib><creatorcontrib>Beecham, Ashley H</creatorcontrib><creatorcontrib>Blanton, Susan H</creatorcontrib><creatorcontrib>Wright, Clinton B</creatorcontrib><creatorcontrib>Sacco, Ralph L</creatorcontrib><creatorcontrib>Wen, Wei</creatorcontrib><creatorcontrib>Thalamuthu, Anbupalam</creatorcontrib><creatorcontrib>Armstrong, Nicola J</creatorcontrib><creatorcontrib>Chong, Elizabeth</creatorcontrib><creatorcontrib>Schofield, Peter R</creatorcontrib><creatorcontrib>Kwok, John B</creatorcontrib><creatorcontrib>van der Grond, Jeroen</creatorcontrib><creatorcontrib>Stott, David J</creatorcontrib><creatorcontrib>Ford, Ian</creatorcontrib><creatorcontrib>Jukema, J. Wouter</creatorcontrib><creatorcontrib>Vernooij, Meike W</creatorcontrib><creatorcontrib>Hofman, Albert</creatorcontrib><creatorcontrib>Uitterlinden, Andre G</creatorcontrib><creatorcontrib>van der Lugt, Aad</creatorcontrib><creatorcontrib>Wittfeld, Katharina</creatorcontrib><creatorcontrib>Grabe, Hans J</creatorcontrib><creatorcontrib>Hosten, Norbert</creatorcontrib><creatorcontrib>von Sarnowski, Bettina</creatorcontrib><creatorcontrib>Voelker, Uwe</creatorcontrib><creatorcontrib>Levi, Christopher</creatorcontrib><creatorcontrib>Jimenez-Conde, Jordi</creatorcontrib><collection>Lirias (KU Leuven Association)</collection><jtitle>NEUROLOGY</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chauhan, Ganesh</au><au>Adams, Hieab H.H</au><au>Satizabal, Claudia L</au><au>Bis, Joshua C</au><au>Teumer, Alexander</au><au>Sargurupremraj, Muralidharan</au><au>Hofer, Edith</au><au>Trompet, Stella</au><au>Hilal, Saima</au><au>Smith, Albert Vernon</au><au>Jian, Xueqiu</au><au>Malik, Rainer</au><au>Traylor, Matthew</au><au>Pulit, Sara L</au><au>Amouyel, Philippe</au><au>Mazoyer, Bernard</au><au>Zhu, Yi-Cheng</au><au>Kaffashian, Sara</au><au>Schilling, Sabrina</au><au>Beecham, Gary W</au><au>Montine, Thomas J</au><au>Schellenberg, Gerard D</au><au>Kjartansson, Olafur</au><au>Gudnason, Vilmundur</au><au>Knopman, David S</au><au>Griswold, Michael E</au><au>Windham, B. Gwen</au><au>Gottesman, Rebecca F</au><au>Mosley, Thomas H</au><au>Schmidt, Reinhold</au><au>Saba, Yasaman</au><au>Schmidt, Helena</au><au>Takeuchi, Fumihiko</au><au>Yamaguchi, Shuhei</au><au>Nabika, Toru</au><au>Kato, Norihiro</au><au>Rajan, Kumar B</au><au>Aggarwal, Neelum T</au><au>De Jager, Philip L</au><au>Evans, Denis A</au><au>Psaty, Bruce M</au><au>Rotter, Jerome I</au><au>Rice, Kenneth</au><au>Lopez, Oscar L</au><au>Liao, Jiemin</au><au>Chen, Christopher</au><au>Cheng, Ching-Yu</au><au>Wong, Tien Y</au><au>Ikram, Mohammad K</au><au>van der Lee, Sven J</au><au>Amin, Najaf</au><au>Chouraki, Vincent</au><au>DeStefano, Anita L</au><au>Aparicio, Hugo J</au><au>Romero, Jose R</au><au>Maillard, Pauline</au><au>DeCarli, Charles</au><au>Wardlaw, Joanna M</au><au>Hernandez, Maria del C. Valdes</au><au>Luciano, Michelle</au><au>Liewald, David</au><au>Deary, Ian J</au><au>Starr, John M</au><au>Bastin, Mark E</au><au>Maniega, Susana Munoz</au><au>Slagboom, P. Eline</au><au>Beekman, Marian</au><au>Deelen, Joris</au><au>Uh, Hae-Won</au><au>Lemmens, Robin</au><au>Brodaty, Henry</au><au>Wright, Margaret J</au><au>Ames, David</au><au>Boncoraglio, Giorgio B</au><au>Hopewell, Jemma C</au><au>Beecham, Ashley H</au><au>Blanton, Susan H</au><au>Wright, Clinton B</au><au>Sacco, Ralph L</au><au>Wen, Wei</au><au>Thalamuthu, Anbupalam</au><au>Armstrong, Nicola J</au><au>Chong, Elizabeth</au><au>Schofield, Peter R</au><au>Kwok, John B</au><au>van der Grond, Jeroen</au><au>Stott, David J</au><au>Ford, Ian</au><au>Jukema, J. Wouter</au><au>Vernooij, Meike W</au><au>Hofman, Albert</au><au>Uitterlinden, Andre G</au><au>van der Lugt, Aad</au><au>Wittfeld, Katharina</au><au>Grabe, Hans J</au><au>Hosten, Norbert</au><au>von Sarnowski, Bettina</au><au>Voelker, Uwe</au><au>Levi, Christopher</au><au>Jimenez-Conde, Jordi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting</atitle><jtitle>NEUROLOGY</jtitle><date>2019-01-29</date><risdate>2019</risdate><volume>92</volume><issue>5</issue><spage>E486</spage><epage>E503</epage><pages>E486-E503</pages><issn>0028-3878</issn><abstract>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.</abstract><pub>LIPPINCOTT WILLIAMS & WILKINS</pub><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-3878 |
| ispartof | NEUROLOGY, 2019-01, Vol.92 (5), p.E486-E503 |
| issn | 0028-3878 |
| language | eng |
| recordid | cdi_kuleuven_dspace_123456789_634974 |
| source | Journals@Ovid Ovid Autoload; Lirias (KU Leuven Association); Alma/SFX Local Collection |
| title | Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T02%3A55%3A40IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-kuleuven&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genetic%20and%20lifestyle%20risk%20factors%20for%20MRI-defined%20brain%20infarcts%20in%20a%20population-based%20setting&rft.jtitle=NEUROLOGY&rft.au=Chauhan,%20Ganesh&rft.date=2019-01-29&rft.volume=92&rft.issue=5&rft.spage=E486&rft.epage=E503&rft.pages=E486-E503&rft.issn=0028-3878&rft_id=info:doi/&rft_dat=%3Ckuleuven%3E123456789_634974%3C/kuleuven%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/&rfr_iscdi=true |