Research ExplorerPublicationsGenetic and lifestyle risk factors for MRI-defined brain inf...

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

Standard

Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting. / 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; Guðnason, 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; Hernández, Maria Del C Valdés; Luciano, Michelle; Liewald, David; Deary, Ian J; Starr, John M; Bastin, Mark E; Muñoz Maniega, Susana; 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, André G; van der Lugt, Aad; Wittfeld, Katharina; Grabe, Hans J; Hosten, Norbert; von Sarnowski, Bettina; Völker, Uwe; Levi, Christopher; Jimenez-Conde, Jordi; Sharma, Pankaj; Sudlow, Cathie L M; Rosand, Jonathan; Woo, Daniel; Cole, John W; Meschia, James F; Slowik, Agnieszka; Thijs, Vincent; Lindgren, Arne; Melander, Olle; Grewal, Raji P; Rundek, Tatjana; Rexrode, Kathy; Rothwell, Peter M; Arnett, Donna K; Jern, Christina; Johnson, Julie A; Benavente, Oscar R; Wasssertheil-Smoller, Sylvia; Lee, Jin-Moo; Wong, Quenna; Mitchell, Braxton D; Rich, Stephen S; McArdle, Patrick F; Geerlings, Mirjam I; van der Graaf, Yolanda; de Bakker, Paul I W; Asselbergs, Folkert W; Srikanth, Velandai; Thomson, Russell; McWhirter, Rebekah; Moran, Chris; Callisaya, Michele; Phan, Thanh; Rutten-Jacobs, Loes C A; Bevan, Steve; Tzourio, Christophe; Mather, Karen A; Sachdev, Perminder S; van Duijn, Cornelia M; Worrall, Bradford B; Dichgans, Martin; Kittner, Steven J; Markus, Hugh S; Ikram, Mohammad A; Fornage, Myriam; Launer, Lenore J; Seshadri, Sudha; Longstreth, W T; Debette, Stéphanie; 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.

In: NEUROLOGY, Vol. 92, No. 5, 29.01.2019, p. e486-e503.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

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 2019, 'Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting', NEUROLOGY, vol. 92, no. 5, pp. e486-e503. https://doi.org/10.1212/WNL.0000000000006851

APA

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., ... 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

Vancouver

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 29;92(5):e486-e503. https://doi.org/10.1212/WNL.0000000000006851

Bibtex

@article{7a036c11ed4940038776ef916483601e,
title = "Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting",
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.",
author = "Ganesh Chauhan and Adams, {Hieab H H} and Satizabal, {Claudia L} and Bis, {Joshua C} and Alexander Teumer and Muralidharan Sargurupremraj and Edith Hofer and Stella Trompet and Saima Hilal and Smith, {Albert Vernon} and Xueqiu Jian and Rainer Malik and Matthew Traylor and Pulit, {Sara L} and Philippe Amouyel and Bernard Mazoyer and Yi-Cheng Zhu and Sara Kaffashian and Sabrina Schilling and Beecham, {Gary W} and Montine, {Thomas J} and Schellenberg, {Gerard D} and Olafur Kjartansson and Vilmundur Gu{\dh}nason and Knopman, {David S} and Griswold, {Michael E} and Windham, {B Gwen} and Gottesman, {Rebecca F} and Mosley, {Thomas H} and Reinhold Schmidt and Yasaman Saba and Helena Schmidt and Fumihiko Takeuchi and Shuhei Yamaguchi and Toru Nabika and Norihiro Kato and Rajan, {Kumar B} and Aggarwal, {Neelum T} and {De Jager}, {Philip L} and Evans, {Denis A} and Psaty, {Bruce M} and Rotter, {Jerome I} and Kenneth Rice and Lopez, {Oscar L} and Jiemin Liao and Christopher Chen and Ching-Yu Cheng and Wong, {Tien Y} and Ikram, {Mohammad K} and {van der Lee}, {Sven J} and Najaf Amin and Vincent Chouraki and DeStefano, {Anita L} and Aparicio, {Hugo J} and Romero, {Jose R} and Pauline Maillard and Charles DeCarli and Wardlaw, {Joanna M} and Hern{\'a}ndez, {Maria Del C Vald{\'e}s} and Michelle Luciano and David Liewald and Deary, {Ian J} and Starr, {John M} and Bastin, {Mark E} and {Mu{\~n}oz Maniega}, Susana and Slagboom, {P Eline} and Marian Beekman and Joris Deelen and Hae-Won Uh and Robin Lemmens and Henry Brodaty and Wright, {Margaret J} and David Ames and Boncoraglio, {Giorgio B} and Hopewell, {Jemma C} and Beecham, {Ashley H} and Blanton, {Susan H} and Wright, {Clinton B} and Sacco, {Ralph L} and Wei Wen and Anbupalam Thalamuthu and Armstrong, {Nicola J} and Elizabeth Chong and Schofield, {Peter R} and Kwok, {John B} and {van der Grond}, Jeroen and Stott, {David J} and Ian Ford and Jukema, {J Wouter} and Vernooij, {Meike W} and Albert Hofman and Uitterlinden, {Andr{\'e} G} and {van der Lugt}, Aad and Katharina Wittfeld and Grabe, {Hans J} and Norbert Hosten and {von Sarnowski}, Bettina and Uwe V{\"o}lker and Christopher Levi and Jordi Jimenez-Conde and Pankaj Sharma and Sudlow, {Cathie L M} and Jonathan Rosand and Daniel Woo and Cole, {John W} and Meschia, {James F} and Agnieszka Slowik and Vincent Thijs and Arne Lindgren and Olle Melander and Grewal, {Raji P} and Tatjana Rundek and Kathy Rexrode and Rothwell, {Peter M} and Arnett, {Donna K} and Christina Jern and Johnson, {Julie A} and Benavente, {Oscar R} and Sylvia Wasssertheil-Smoller and Jin-Moo Lee and Quenna Wong and Mitchell, {Braxton D} and Rich, {Stephen S} and McArdle, {Patrick F} and Geerlings, {Mirjam I} and {van der Graaf}, Yolanda and {de Bakker}, {Paul I W} and Asselbergs, {Folkert W} and Velandai Srikanth and Russell Thomson and Rebekah McWhirter and Chris Moran and Michele Callisaya and Thanh Phan and Rutten-Jacobs, {Loes C A} and Steve Bevan and Christophe Tzourio and Mather, {Karen A} and Sachdev, {Perminder S} and {van Duijn}, {Cornelia M} and Worrall, {Bradford B} and Martin Dichgans and Kittner, {Steven J} and Markus, {Hugh S} and Ikram, {Mohammad A} and Myriam Fornage and Launer, {Lenore J} and Sudha Seshadri and Longstreth, {W T} and St{\'e}phanie Debette and {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}",
note = "Copyright {\textcopyright} 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.",
year = "2019",
month = jan,
day = "29",
doi = "10.1212/WNL.0000000000006851",
language = "English",
volume = "92",
pages = "e486--e503",
journal = "NEUROLOGY",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

RIS

TY - JOUR

T1 - Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting

AU - Chauhan, Ganesh

AU - Adams, Hieab H H

AU - Satizabal, Claudia L

AU - Bis, Joshua C

AU - Teumer, Alexander

AU - Sargurupremraj, Muralidharan

AU - Hofer, Edith

AU - Trompet, Stella

AU - Hilal, Saima

AU - Smith, Albert Vernon

AU - Jian, Xueqiu

AU - Malik, Rainer

AU - Traylor, Matthew

AU - Pulit, Sara L

AU - Amouyel, Philippe

AU - Mazoyer, Bernard

AU - Zhu, Yi-Cheng

AU - Kaffashian, Sara

AU - Schilling, Sabrina

AU - Beecham, Gary W

AU - Montine, Thomas J

AU - Schellenberg, Gerard D

AU - Kjartansson, Olafur

AU - Guðnason, Vilmundur

AU - Knopman, David S

AU - Griswold, Michael E

AU - Windham, B Gwen

AU - Gottesman, Rebecca F

AU - Mosley, Thomas H

AU - Schmidt, Reinhold

AU - Saba, Yasaman

AU - Schmidt, Helena

AU - Takeuchi, Fumihiko

AU - Yamaguchi, Shuhei

AU - Nabika, Toru

AU - Kato, Norihiro

AU - Rajan, Kumar B

AU - Aggarwal, Neelum T

AU - De Jager, Philip L

AU - Evans, Denis A

AU - Psaty, Bruce M

AU - Rotter, Jerome I

AU - Rice, Kenneth

AU - Lopez, Oscar L

AU - Liao, Jiemin

AU - Chen, Christopher

AU - Cheng, Ching-Yu

AU - Wong, Tien Y

AU - Ikram, Mohammad K

AU - van der Lee, Sven J

AU - Amin, Najaf

AU - Chouraki, Vincent

AU - DeStefano, Anita L

AU - Aparicio, Hugo J

AU - Romero, Jose R

AU - Maillard, Pauline

AU - DeCarli, Charles

AU - Wardlaw, Joanna M

AU - Hernández, Maria Del C Valdés

AU - Luciano, Michelle

AU - Liewald, David

AU - Deary, Ian J

AU - Starr, John M

AU - Bastin, Mark E

AU - Muñoz Maniega, Susana

AU - Slagboom, P Eline

AU - Beekman, Marian

AU - Deelen, Joris

AU - Uh, Hae-Won

AU - Lemmens, Robin

AU - Brodaty, Henry

AU - Wright, Margaret J

AU - Ames, David

AU - Boncoraglio, Giorgio B

AU - Hopewell, Jemma C

AU - Beecham, Ashley H

AU - Blanton, Susan H

AU - Wright, Clinton B

AU - Sacco, Ralph L

AU - Wen, Wei

AU - Thalamuthu, Anbupalam

AU - Armstrong, Nicola J

AU - Chong, Elizabeth

AU - Schofield, Peter R

AU - Kwok, John B

AU - van der Grond, Jeroen

AU - Stott, David J

AU - Ford, Ian

AU - Jukema, J Wouter

AU - Vernooij, Meike W

AU - Hofman, Albert

AU - Uitterlinden, André G

AU - van der Lugt, Aad

AU - Wittfeld, Katharina

AU - Grabe, Hans J

AU - Hosten, Norbert

AU - von Sarnowski, Bettina

AU - Völker, Uwe

AU - Levi, Christopher

AU - Jimenez-Conde, Jordi

AU - Sharma, Pankaj

AU - Sudlow, Cathie L M

AU - Rosand, Jonathan

AU - Woo, Daniel

AU - Cole, John W

AU - Meschia, James F

AU - Slowik, Agnieszka

AU - Thijs, Vincent

AU - Lindgren, Arne

AU - Melander, Olle

AU - Grewal, Raji P

AU - Rundek, Tatjana

AU - Rexrode, Kathy

AU - Rothwell, Peter M

AU - Arnett, Donna K

AU - Jern, Christina

AU - Johnson, Julie A

AU - Benavente, Oscar R

AU - Wasssertheil-Smoller, Sylvia

AU - Lee, Jin-Moo

AU - Wong, Quenna

AU - Mitchell, Braxton D

AU - Rich, Stephen S

AU - McArdle, Patrick F

AU - Geerlings, Mirjam I

AU - van der Graaf, Yolanda

AU - de Bakker, Paul I W

AU - Asselbergs, Folkert W

AU - Srikanth, Velandai

AU - Thomson, Russell

AU - McWhirter, Rebekah

AU - Moran, Chris

AU - Callisaya, Michele

AU - Phan, Thanh

AU - Rutten-Jacobs, Loes C A

AU - Bevan, Steve

AU - Tzourio, Christophe

AU - Mather, Karen A

AU - Sachdev, Perminder S

AU - van Duijn, Cornelia M

AU - Worrall, Bradford B

AU - Dichgans, Martin

AU - Kittner, Steven J

AU - Markus, Hugh S

AU - Ikram, Mohammad A

AU - Fornage, Myriam

AU - Launer, Lenore J

AU - Seshadri, Sudha

AU - Longstreth, W T

AU - Debette, Stéphanie

AU - 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) C

N1 - Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

PY - 2019/1/29

Y1 - 2019/1/29

N2 - 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.

AB - 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.

U2 - 10.1212/WNL.0000000000006851

DO - 10.1212/WNL.0000000000006851

M3 - SCORING: Journal article

C2 - 30651383

VL - 92

SP - e486-e503

JO - NEUROLOGY

JF - NEUROLOGY

SN - 0028-3878

IS - 5

ER -