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

Artikel i vetenskaplig tidskrift
Författare Ganesh Chauhan
Hieab H H Adams
Claudia L Satizabal
Joshua C Bis
Alexander Teumer
Muralidharan Sargurupremraj
Edith Hofer
Stella Trompet
Saima Hilal
Albert Vernon Smith
Xueqiu Jian
Rainer Malik
Matthew Traylor
Sara L Pulit
Philippe Amouyel
Bernard Mazoyer
Yi-Cheng Zhu
Sara Kaffashian
Sabrina Schilling
Gary W Beecham
Thomas J Montine
Gerard D Schellenberg
Olafur Kjartansson
Vilmundur Guðnason
David S Knopman
Michael E Griswold
B Gwen Windham
Rebecca F Gottesman
Thomas H Mosley
Reinhold Schmidt
Yasaman Saba
Helena Schmidt
Fumihiko Takeuchi
Shuhei Yamaguchi
Toru Nabika
Norihiro Kato
Kumar B Rajan
Neelum T Aggarwal
Philip L De Jager
Denis A Evans
Bruce M Psaty
Jerome I Rotter
Kenneth Rice
Oscar L Lopez
Jiemin Liao
Christopher Chen
Ching-Yu Cheng
Tien Y Wong
Mohammad K Ikram
Sven J van der Lee
Najaf Amin
Vincent Chouraki
Anita L DeStefano
Hugo J Aparicio
Jose R Romero
Pauline Maillard
Charles DeCarli
Joanna M Wardlaw
Maria Del C Valdés Hernández
Michelle Luciano
David Liewald
Ian J Deary
John M Starr
Mark E Bastin
Susana Muñoz Maniega
P Eline Slagboom
Marian Beekman
Joris Deelen
Hae-Won Uh
Robin Lemmens
Henry Brodaty
Margaret J Wright
David Ames
Giorgio B Boncoraglio
Jemma C Hopewell
Ashley H Beecham
Susan H Blanton
Clinton B Wright
Ralph L Sacco
Wei Wen
Anbupalam Thalamuthu
Nicola J Armstrong
Elizabeth Chong
Peter R Schofield
John B Kwok
Jeroen van der Grond
David J Stott
Ian Ford
J Wouter Jukema
Meike W Vernooij
Albert Hofman
André G Uitterlinden
Aad van der Lugt
Katharina Wittfeld
Hans J Grabe
Norbert Hosten
Bettina von Sarnowski
Uwe Völker
Christopher Levi
Jordi Jimenez-Conde
Pankaj Sharma
Cathie L M Sudlow
Jonathan Rosand
Daniel Woo
John W Cole
James F Meschia
Agnieszka Slowik
Vincent Thijs
Arne Lindgren
Olle Melander
Raji P Grewal
Tatjana Rundek
Kathy Rexrode
Peter M Rothwell
Donna K Arnett
Christina Jern
Julie A Johnson
Oscar R Benavente
Sylvia Wasssertheil-Smoller
Jin-Moo Lee
Quenna Wong
Braxton D Mitchell
Stephen S Rich
Patrick F McArdle
Mirjam I Geerlings
Yolanda van der Graaf
Paul I W de Bakker
Folkert W Asselbergs
Velandai Srikanth
Russell Thomson
Rebekah McWhirter
Chris Moran
Michele Callisaya
Thanh Phan
Loes C A Rutten-Jacobs
Steve Bevan
Christophe Tzourio
Karen A Mather
Perminder S Sachdev
Cornelia M van Duijn
Bradford B Worrall
Martin Dichgans
Steven J Kittner
Hugh S Markus
Mohammad A Ikram
Myriam Fornage
Lenore J Launer
Sudha Seshadri
W T Longstreth
Stéphanie Debette
Katarina Jood
Publicerad i Neurology
ISSN 1526-632X
Publiceringsår 2019
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap
Språk en
Länkar dx.doi.org/10.1212/WNL.000000000000...
www.ncbi.nlm.nih.gov/entrez/query.f...
Ämneskategorier Neurologi

Sammanfattning

To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts.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.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.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.

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