Novel blood pressure locus and gene discovery using gwas and expression datasets from blood and the kidney

LBC1921: Phenotype collection in the Lothian Birth Cohort 1921 was supported by the UK’s Biotechnology and Biological Sciences Research Council (BBSRC), The Royal Society, and The Chief Scientist Office of the Scottish Government. Genotyping was funded by the BBSRC. The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1). Funding from the BBSRC and Medical Research Council (MRC) is gratefully acknowledged. We thank the Lothian Birth Cohort 1921 participants and team members who contributed to these studies.

LBC1936: Phenotype collection in the Lothian Birth Cohort 1936 was supported by Age UK (The Disconnected Mind project).  Genotyping was funded by the BBSRC. The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1). Funding from the BBSRC and Medical Research Council (MRC) is gratefully acknowledged. We thank the Lothian Birth Cohort 1936 participants and team members who contributed to these studies.

Lifelines Cohort Study: The LifeLines Cohort Study, and generation and management of GWAS genotype data for the LifeLines Cohort Study is supported by the Netherlands Organization of Scientific Research NWO (grant 175.010.2007.006), the Economic Structure Enhancing Fund (FES) of the Dutch government, the Ministry of Economic Affairs, the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the Northern Netherlands Collaboration of Provinces (SNN), the Province of Groningen, University Medical Center Groningen, the University of Groningen, Dutch Kidney Foundation and Dutch Diabetes Research Foundation. The authors wish to acknowledge the services of the Lifelines Cohort Study, the contributing research centers delivering data to Lifelines, and all the study participants.

LOLIPOP: The LOLIPOP study is funded by the British Heart Foundation (SP/04/002), the Medical Research Council (G0601966, G0700931), the Wellcome Trust (084723/Z/08/Z), the NIHR (RP-PG-0407-10371), European Union FP7 (EpiMigrant, 279143) and Action on Hearing Loss (G51). The LOLIPOP study is supported by the National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre Imperial College Healthcare NHS Trust. The work was carried out in part at the NIHR/Wellcome Trust Imperial Clinical Research Facility. We thank the participants and research staff who made the study possible.

MESA: This research was supported by the Multi-Ethnic Study of Atherosclerosis (MESA) contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169 and by grants UL1-TR-000040 and UL1-RR-025005 from NCRR . Funding for MESA SHARe genotyping was provided by NHLBI Contract N02-HL-6-4278. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center.

MICROS: The MICROS study was supported by the Ministry of Health and Department of Innovation, Research and University of the Autonomous Province of Bolzano, the South Tyrolean Sparkasse Foundation, and the European Union framework program 6 EUROSPAN project (contract no. LSHG-CT-2006-018947) For the MICROS study, we thank the primary care practitioners Raffaela Stocker, Stefan Waldner, Toni Pizzecco, Josef Plangger, Ugo Marcadent, and the personnel of the Hospital of Silandro (Department of Laboratory Medicine) for their participation and collaboration in the research project.

NEO: The NEO study is supported by the participating Departments, the Division and the Board of Directors of the Leiden University Medical Center, and by the Leiden University, Research Profile Area Vascular and Regenerative Medicine. Dennis Mook-Kanamori is supported by Dutch Science Organization (ZonMW-VENI Grant 916.14.023). The authors of the NEO study thank all individuals who participated in the Netherlands Epidemiology in Obesity study, all participating general practitioners for inviting eligible participants and all research nurses for collection of the data. We thank the NEO study group, Pat van Beelen, Petra Noordijk and Ingeborg de Jonge for the coordination, lab and data management of the NEO study. The genotyping in the NEO study was supported by the Centre National de Génotypage (Paris, France), headed by Jean-Francois Deleuze.

NESDA: Funding was obtained from the Netherlands Organization for Scientific Research (Geestkracht program grant 10-000-1002); the Center for Medical Systems Biology (CSMB, NOW Genomics), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL), VU University’s Institutes for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam, University Medical Center Groningen, Leiden University Medical Center, National Institutes of Health (NIH, R01D0042157-01A, MH081802, Grand Opportunity grants 1RC2 MH089951 and 1RC2 MH089995). Part of the genotyping and analyses were funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health. Computing was supported by BiG Grid, the Dutch e-Science Grid, which is financially supported by NWO.

NSPHS: The Northern Swedish Population Health Study (NSPHS) was funded by the Swedish Medical Research Council (Project Number K2007-66X-20270-01-3, 2011-5252, 2012-2884 and 2011-2354), the Foundation for Strategic Research (SSF). NSPHS as part of EUROSPAN (European Special Populations Research Network) was also supported by the European Commission FP6 STRP grant number 01947 (LSHG-CT-2006-01947). This work has also been supported by the Swedish Society for Medical Research (SSMF), and the Swedish Medical Research Council (#2015-03327) We are grateful for the contribution of district nurse Svea Hennix for data collection and Inger Jonasson for logistics and coordination of the health survey. We also thank all the participants from the community for their interest and willingness to contribute to this study.

NTR: Funding was obtained from the Netherlands Organization for Scientific Research (NWO) and The Netherlands Organisation for Health Research and Development (ZonMW) grants 904-61-090, 985-10-002, 904-61-193,480-04-004, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192, Biobanking and Biomolecular Resources Research Infrastructure (BBMRI –NL, 184.021.007); the Netherlands Heart Foundation grants 86.083 and 88.042 and 90.313; the VU Institute for Health and Care Research (EMGO+ ); the European Community's Seventh Framework Program (FP7/2007-2013), ENGAGE (HEALTH-F4-2007-201413); the European Research Council (ERC Advanced, 230374), the Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06), the Avera Institute, Sioux Falls, South Dakota (USA) and the National Institutes of Health (NIH, R01D0042157-01A, MH081802; Grand Opportunity grant 1RC2 MH089951). Part of the genotyping and analyses were funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health. Computing was supported by BiG Grid, the Dutch e-Science Grid, which is financially supported by NWO. "

ORCADES: ORCADES was supported by the Chief Scientist Office of the Scottish Government, the Royal Society, the MRC Human Genetics Unit, Arthritis Research UK and the European Union framework program 6 EUROSPAN project (contract no. LSHG-CT-2006-018947). DNA extractions were performed at the Wellcome Trust Clinical Research Facility in Edinburgh. We would like to acknowledge the invaluable contributions of Lorraine Anderson and the research nurses in Orkney, the administrative team in Edinburgh and the people of Orkney.

PIVUS: This project was supported by Knut and Alice Wallenberg Foundation (Wallenberg Academy Fellow), European Research Council (ERC Starting Grant), Swedish Diabetes Foundation (grant no. 2013-024), Swedish Research Council (grant no. 2012-1397), and Swedish Heart-Lung Foundation (20120197). The computations were performed on resources provided by SNIC through Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) under Project b2011036. Genetic data analysis was funded by the Wellcome Trust under awards WT098017 and WT090532. We thank the SNP&SEQ Technology Platform in Uppsala (www.genotyping.se) for excellent genotyping.

PROCARDIS: PROCARDIS was supported by the European Community Sixth Framework Program (LSHM-CT- 2007-037273), AstraZeneca, the British Heart Foundation, the Swedish Research Council, the Knut and Alice Wallenberg Foundation, the Swedish Heart-Lung Foundation, the Torsten and Ragnar Söderberg Foundation, the Strategic Cardiovascular Program of Karolinska Institutet and Stockholm County Council, the Foundation for Strategic Research and the Stockholm County Council (560283). M.F and H.W acknowledge the support of the Wellcome Trust core award (090532/Z/09/Z) and M.F, H.W, the BHF Centre of Research Excellence (RE/13/1/30181). A.G, H.W acknowledge European Union Seventh Framework Programme FP7/2007-2013 under grant agreement no. HEALTH-F2-2013-601456 (CVGenes@Target) & and A.G, the Wellcome Trust Institutional strategic support fund. PROCARDIS was supported by the European Community Sixth Framework Program (LSHM-CT- 2007-037273), AstraZeneca, the British Heart Foundation, the Swedish Research Council, the Knut and Alice Wallenberg Foundation, the Swedish Heart-Lung Foundation, the Torsten and Ragnar Söderberg Foundation, the Strategic Cardiovascular Program of Karolinska Institutet and Stockholm County Council, the Foundation for Strategic Research and the Stockholm County Council (560283). M.F and H.W acknowledge the support of the Wellcome Trust core award (090532/Z/09/Z) and M.F, H.W, the BHF Centre of Research Excellence (RE/13/1/30181). A.G, H.W acknowledge European Union Seventh Framework Programme FP7/2007-2013 under grant agreement no. HEALTH-F2-2013-601456 (CVGenes@Target) & and A.G, the Wellcome Trust Institutional strategic support fund.

PROSPER: The PROSPER study was supported by an investigator initiated grant obtained from Bristol-Myers Squibb. Prof. Dr. J. W. Jukema is an Established Clinical Investigator of the Netherlands Heart Foundation (grant 2001 D 032). Support for genotyping was provided by the seventh framework program of the European commission (grant 223004) and by the Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging grant 050-060-810).

RS: The generation and management of GWAS genotype data for the Rotterdam Study (RS I, RS II, RS III) was executed by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. The GWAS datasets are supported by the Netherlands Organisation of Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012), the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA), project nr. 050-060-810. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. We thank Pascal Arp, Mila Jhamai, Marijn Verkerk, Lizbeth Herrera and Marjolein Peters, MSc, and Carolina Medina-Gomez, MSc, for their help in creating the GWAS database, and Karol Estrada, PhD, Yurii Aulchenko, PhD, and Carolina Medina-Gomez, MSc, for the creation and analysis of imputed data.The authors are grateful to the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists.

SHIP: SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania, and the network ‘Greifswald Approach to Individualized Medicine (GANI_MED)’ funded by the Federal Ministry of Education and Research (grant 03IS2061A). Genome-wide data have been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012) and a joint grant from Siemens Healthcare, Erlangen, Germany and the Federal State of Mecklenburg- West Pomerania. The University of Greifswald is a member of the Caché Campus program of the InterSystems GmbH.

Three City- Dijon: The 3-City Study is conducted under a partnership agreement among the Institut National de la Santé et de la Recherche Médicale (INSERM), the University of Bordeaux, and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study is also supported by the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, Mutuelle Générale de l’Education Nationale (MGEN), Institut de la Longévité, Conseils Régionaux of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research–INSERM Programme “Cohortes et collections de données biologiques.” This work was supported by the National Foundation for Alzheimer’s Disease and Related Disorders, the Institut Pasteur de Lille, the Centre National de Génotypage and the LABEX (Laboratory of Excellence program investment for the future) DISTALZ - Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer’s disease. Ganesh Chauhan, Christophe Tzourio and Stéphanie Debette are supported by a grant from the Fondation Leducq. We thank Philippe Amouyel and the UMR1167 Inserm Univ Lille Institut Pasteur de Lille for providing the 3C Dijon cohort SNP replication data funded by a grant from the French National Foundation on Alzheimer’s disease and related disorders.

UKHLS: This work was funded through generous grants from the Economic & Social Research Council (ES/H029745/1) and the Wellcome Trust (WT098051).

TRAILS: This research is part of the TRacking Adolescents' Individual Lives Survey (TRAILS). Participating centers of TRAILS include the University Medical Center and University of Groningen, the Erasmus University Medical Center Rotterdam, the University of Utrecht, the Radboud Medical Center Nijmegen, and the Parnassia Bavo group, all in the Netherlands. TRAILS has been financially supported by various grants from the Netherlands Organization for Scientific Research NWO (Medical Research Council program grant GB-MW 940-38-011; ZonMW Brainpower grant 100-001-004; ZonMw Risk Behavior and Dependence grants 60-60600-97-118; ZonMw Culture and Health grant 261-98-710; Social Sciences Council medium-sized investment grants GB-MaGW 480-01-006 and GB-MaGW 480-07-001; Social Sciences Council project grants GB-MaGW 452-04-314 and GB-MaGW 452-06-004; NWO large-sized investment grant 175.010.2003.005; NWO Longitudinal Survey and Panel Funding 481-08-013 and 481-11-001), the Dutch Ministry of Justice (WODC), the European Science Foundation (EuroSTRESS project FP-006), Biobanking and Biomolecular Resources Research Infrastructure BBMRI-NL (CP 32), and the participating universities. Statistical analyses were carried out on the Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and financially supported by the Netherlands Scientific Organization (NWO 480-05-003 PI: Posthuma) along with a supplement from the Dutch Brain Foundation and the VU University Amsterdam.

TwinGene: This project was supported by grants from the Ministry for Higher Education, the Swedish Research Council (M-2005-1112 and 2009-2298), GenomEUtwin (EU/QLRT-2001-01254; QLG2-CT-2002-01254), NIH grant DK U01-066134, Knut and Alice Wallenberg Foundation (Wallenberg Academy Fellow), European Research Council (ERC Starting Grant), Swedish Diabetes Foundation (grant no. 2013-024), Swedish Research Council (grant no. 2012-1397), and Swedish Heart-Lung Foundation (20120197). We thank the SNP&SEQ Technology Platform in Uppsala (www.genotyping.se) for excellent genotyping. The computations were performed on resources provided by SNIC through Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) under Project b2011036.

TwinsUK: The study was funded by the Wellcome Trust; European Community’s Seventh Framework Programme (FP7/2007-2013). The study also receives support from the National Institute for Health Research (NIHR) BioResource Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London (guysbrc-2012-1). We thank the staff from the Genotyping Facilities at the Wellcome Trust Sanger Institute for sample preparation, quality control, and genotyping; Le Centre National de Génotypage, France, for genotyping; Duke University, NC, USA, for genotyping; and the Finnish Institute of Molecular Medicine, Finnish Genome Center, University of Helsinki. Genotyping was also done by CIDR as part of an NEI/NIH project grant

UK Biobank_Cardiometabolic Consortium: This research has been conducted using the UK Biobank Resource under application number 236. H.R.W., C.P.C and M.R.B. were funded by the National Institutes for Health Research (NIHR) as part of the portfolio of translational research of the NIHR Biomedical Research Unit at Barts MR was funded by the National Institute for Health Research (NIHR) Biomedical Research Unit in Cardiovascular Disease at Barts. MR is recipient from China Scholarship Council (No. 2011632047). B.M. holds an MRC eMedLab Medical Bioinformatics Career Development Fellowship, funded from award MR/L016311/1. PE was funded by the National Institutes for Health Research (NIHR) Imperial College Health Care NHS Trust and Imperial College London Biomedical Research Centre, the UK Medical Research Council and Public Health England as Director of the MRC-PHE Centre for Environment and Health, and the NIHR Health Protection Research Unit on the Health Effects of Environmental Hazards. Some of this work used computing resources provided by the Medical Research Council-funded UK MEDical Bioinformatics partnership programme (UK MED-BIO) (MR/L01632X/1).

ULSAM: This project was supported by Knut and Alice Wallenberg Foundation (Wallenberg Academy Fellow), European Research Council (ERC Starting Grant), Swedish Diabetes Foundation (grant no. 2013-024), Swedish Research Council (grant no. 2012-1397), and Swedish Heart-Lung Foundation (20120197). The computations were performed on resources provided by SNIC through Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) under Project b2011036. Genotyping was funded by the Wellcome Trust under award WT064890. Analysis of genetic data was funded by the Wellcome Trust under awards WT098017 and WT090532. Andrew P. Morris is a Wellcome Trust Senior Research Fellow in Basic Biomedical Science (WT098017). We thank the SNP&SEQ Technology Platform in Uppsala (www.genotyping.se) for excellent genotyping.

WGHS: The WGHS is supported by the National Heart, Lung, and Blood Institute (HL043851, HL080467, HL09935) and the National Cancer Institute (CA047988 and UM1CA182913) with collaborative scientific support and funding for genotyping provided by Amgen.

YFS: The Young Finns Study has been financially supported by the Academy of Finland: grants 286284, 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117787 (Gendi), and 41071 (Skidi); the Social Insurance Institution of Finland; Kuopio, Tampere and Turku University Hospital Medical Funds (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research ; Finnish Cultural Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; and Diabetes Research Foundation of Finnish Diabetes Association. The expert technical assistance in the statistical analyses by Irina Lisinen is gratefully acknowledged.