Journal article

A Novel MMP12 Locus Is Associated with Large Artery Atherosclerotic Stroke Using a Genome-Wide Age-at-Onset Informed Approach

Matthew Traylor, Kari-Matti Makela, Laura L Kilarski, Elizabeth G Holliday, William J Devan, Mike A Nalls, Kerri L Wiggins, Wei Zhao, Yu-Ching Cheng, Sefanja Achterberg, Rainer Malik, Cathie Sudlow, Steve Bevan, Emma Raitoharju, Niku Oksala, Vincent Thijs, Robin Lemmens, Arne Lindgren, Agnieszka Slowik, Jane M Maguire Show all

PLoS Genetics | PUBLIC LIBRARY SCIENCE | Published : 2014

Grants

Awarded by Wellcome Trust, as part of the Wellcome Trust Case Control Consortium 2 project


Awarded by Netherlands Heart Foundation


Awarded by Dutch Brain Foundation


Awarded by Australian National and Medical Health Research Council (NHMRC)


Awarded by Australian National Heart Foundation (NHF)


Awarded by National Institutes of Health Genes, Environment and Health Initiative (GEI) Grant


Awarded by Mid-Atlantic Nutrition and Obesity Research Center


Awarded by National Institutes of Health


Awarded by NIH Office of Research on Women's Health


Awarded by NHLBI


Awarded by Intramural Research Program of the National Institute on Aging, NIH project


Awarded by NIH-NINDS Grant


Awarded by National Institute of Neurological Disorders and Stroke


Awarded by American Heart Association/Bugher Foundation Centers for Stroke Prevention Research


Awarded by National Heart, Lung, and Blood Institute's STAMPEED genomics research program


Awarded by National Center for Research Resources


Awarded by Italian Ministry of Health


Awarded by FP7 European Union project


Awarded by Medical Research Council


Awarded by European Union


Awarded by Tampere University Hospital Medical Fund


Awarded by Stroke Association


Funding Acknowledgements

The principal funding for this study was provided by the Wellcome Trust, as part of the Wellcome Trust Case Control Consortium 2 project (085475/B/08/Z and 085475/Z/08/Z and WT084724MA). HSM is supported by an NIHR Senior Investigator award and the NIHR Biomedical Research Centre at Cambridge. We acknowledge support from the National Institutes of Health Research Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. The PROMISe Study (The Netherlands) was made possible, in part, by a Complementation Grant to PIWdB from the Biobanking and Biomolecular Resources Research Infrastructure in the Netherlands (BBMRI-NL). SA is supported in part by a grant from the Netherlands Heart Foundation (grant no. 2005B031) and a grant from the Dutch Brain Foundation (project 2008(1).10). The Australian Stroke Genetics Collaboration (ASGC) Australian population control data was derived from the Hunter Community Study. We also thank the University of Newcastle for funding and the men and women of the Hunter region who participated in this study. This research was funded by grants from the Australian National and Medical Health Research Council (NHMRC Project Grant ID: 569257), the Australian National Heart Foundation (NHF Project Grant ID: G 04S 1623), the University of Newcastle, the Gladys M Brawn Fellowship scheme and the Vincent Fairfax Family Foundation in Australia. EGH is supported by the Australian NHMRC Fellowship scheme. The Genetics of Early Onset Stroke (GEOS) Study, Baltimore, USA was supported by the National Institutes of Health Genes, Environment and Health Initiative (GEI) Grant U01 HG004436, as part of the GENEVA consortium under GEI, with additional support provided by the Mid-Atlantic Nutrition and Obesity Research Center (P30 DK072488); and the Office of Research and Development, Medical Research Service, and the Baltimore Geriatrics Research, Education, and Clinical Center of the Department of Veterans Affairs. Genotyping services were provided by the Johns Hopkins University Center for Inherited Disease Research (CIDR), which is fully funded through a federal contract from the National Institutes of Health to the Johns Hopkins University (contract number HHSN268200782096C). Assistance with data cleaning was provided by the GENEVA Coordinating Center (U01 HG 004446; PI Bruce S Weir). Study recruitment and assembly of datasets were supported by a Cooperative Agreement with the Division of Adult and Community Health, Centers for Disease Control and by grants from the National Institute of Neurological Disorders and Stroke (NINDS) and the NIH Office of Research on Women's Health (R01 NS45012, U01 NS069208-01). The Heart and Vascular Health Study (HVH) research reported in this article was funded by NHLBI grants R01 HL085251 and R01 HL073410 The Ischemic Stroke Genetics Study (ISGS)/Siblings With Ischemic Stroke Study (SWISS) study was supported in part by the Intramural Research Program of the National Institute on Aging, NIH project Z01 AG-000954-06. ISGS/SWISS used samples and clinical data from the NIH-NINDS Human Genetics Resource Center DNA and Cell Line Repository (http://ccr.coriell.org/ninds), human subjects protocol numbers 2003-081 and 2004-147. ISGS/SWISS used stroke-free participants from the Baltimore Longitudinal Study of Aging (BLSA) as controls.The inclusion of BLSA samples was supported in part by the Intramural Research Program of the National Institute on Aging, NIH project Z01 AG-000015-50, human subjects protocol number 2003-078. The ISGS study was funded by NIH-NINDS Grant R01 NS-42733 (JFM, P. I.). The SWISS study was funded by NIH-NINDS Grant R01 NS-39987 (JFM, P. I.). This study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the NIH (http://biowulf.nih.gov). The MGH Genes Affecting Stroke Risk and Outcome Study (MGH-GASROS) GASROS was supported by The National Institute of Neurological Disorders and Stroke (U01 NS069208), the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research 0775010N, the National Institutes of Health and National Heart, Lung, and Blood Institute's STAMPEED genomics research program (R01 HL087676) and a grant from the National Center for Research Resources. The Broad Institute Center for Genotyping and Analysis is supported by grant U54 RR020278 from the National Center for Research resources. Milano - Besta Stroke Register Collection and genotyping of the Milan cases within CEDIR were supported by Annual Research Funding of the Italian Ministry of Health (Grant Numbers: RC 2007/LR6, RC 2008/LR6; RC 2009/LR8; RC 2010/LR8). FP6 LSHM-CT-2007-037273 for the PROCARDIS control samples. The Wellcome Trust Case-Control Consortium 2 (WTCCC2) The principal funding for the WTCCC2 stroke study was provided by the Wellcome Trust, as part of the Wellcome Trust Case Control Consortium 2 project (085475/B/08/Z and 085475/Z/08/Z and WT084724MA). The Stroke Association provided additional support for collection of some of the St George's, London cases. The Oxford cases were collected as part of the Oxford Vascular Study which is funded by the Medical Research Council, Stroke Association, Dunhill Medical Trust, National Institute of Health Research (NIHR) and the NIHR Biomedical Research Centre, Oxford. PMR has a Wellcome Trust Senior Investigator Award and an NIHR Senior Investigator Award. The Edinburgh Stroke Study was supported by the Wellcome Trust (clinician scientist award to CS), and the Binks Trust. Sample processing occurred in the Genetics Core Laboratory of the Wellcome Trust Clinical Research Facility, Western General Hospital, Edinburgh. This work was supported by grants received from the German Federal Ministry of Education and Research (BMBF) in the context of the e: Med program (e:AtheroSysMed) and the FP7 European Union project CVgenes@target (261123) to Martin Dichgans. Much of the neuroimaging occurred in the Scottish Funding Council Brain Imaging Research Centre (www.sbirc.ed.ac.uk), Division of Clinical Neurosciences, University of Edinburgh, a core area of the Wellcome Trust Clinical Research Facility and part of the SINAPSE (Scottish Imaging Network - A Platform for Scientific Excellence) collaboration (www.sinapse.ac.uk), funded by the Scottish Funding Council and the Chief Scientist Office. Collection of the Munich cases and data analysis was supported by the Vascular Dementia Research Foundation. This work made use of data and samples generated by the 1958 Birth Cohort (NCDS). Access to these resources was enabled via the 58READIE Project funded by Wellcome Trust and Medical Research Council (grant numbers WT095219MA and G1001799). A full list of the financial, institutional and personal contributions to the development of the 1958 Birth Cohort Biomedical resource is available at http://www2.le.ac.uk/projects/birthcohort.Tampere Vascular Study (TVS) was supported by the European Union 7th Framework Programme funding for the AtheroRemo project [201668], the Finnish Foundation of Cardiovascular Research (TL), the Finnish Cultural Foundation, the Tampere Tuberculosis Foundation, the Emil Aaltonen Foundation (NO & TL), the Tampere University Hospital Medical Fund (grant 9M048 and 9N035) and the the Foundation of Clinical Chemistry. Immunochip case data for UK, Polish, Belgian, German and Swedish cohorts was genotyped by the Sanger Centre, Cambridge, UK as part of the Wellcome Trust Case Control Consortium 2 project (085475/B/08/Z and 085475/Z/08/Z and WT084724MA), as were the UK and Polish control cohorts. German Control Genotypes was provided through the POPGEN Consortium. Swedish Immunochip Control Samples were provided by the Swedish SLE network and the Uppsala Bioresource. Belgian Immunochip Control Sample Genotypes were provided through the efforts of the International Multiple Sclerosis Genetics Consortium (IMSGC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.