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Coronary Artery Disease: HELP
Articles by Ida Surakka
Based on 7 articles published since 2009
(Why 7 articles?)
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Between 2009 and 2019, Ida Surakka wrote the following 7 articles about Coronary Artery Disease.
 
+ Citations + Abstracts
1 Article The Contribution of GWAS Loci in Familial Dyslipidemias. 2016

Ripatti, Pietari / Rämö, Joel T / Söderlund, Sanni / Surakka, Ida / Matikainen, Niina / Pirinen, Matti / Pajukanta, Päivi / Sarin, Antti-Pekka / Service, Susan K / Laurila, Pirkka-Pekka / Ehnholm, Christian / Salomaa, Veikko / Wilson, Richard K / Palotie, Aarno / Freimer, Nelson B / Taskinen, Marja-Riitta / Ripatti, Samuli. ·Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland. · Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America. · Psychiatric & Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, United States of America. · Research Programs Unit, Diabetes & Obesity, University of Helsinki, and Heart and Lung Centre, Helsinki University Hospital, Helsinki, Finland. · Endocrinology, Abdominal Center, Helsinki University Hospital, Helsinki, Finland. · Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California Los Angeles (UCLA), Los Angeles, California, United States of America. · National Institute for Health and Welfare, Helsinki, Finland. · Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, California, United States of America. · Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland. · Department of Medical Genetics, University of Helsinki, Helsinki, Finland. · McDonnell Genome Institute, Washington University School of Medicine, St. Louis, Missouri, United States of America. · Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America. · The Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America. · Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, United States of America. · Department of Public Health, Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland. · Wellcome Trust Sanger Institute, Cambridge, United Kingdom. ·PLoS Genet · Pubmed #27227539.

ABSTRACT: Familial combined hyperlipidemia (FCH) is a complex and common familial dyslipidemia characterized by elevated total cholesterol and/or triglyceride levels with over five-fold risk of coronary heart disease. The genetic architecture and contribution of rare Mendelian and common variants to FCH susceptibility is unknown. In 53 Finnish FCH families, we genotyped and imputed nine million variants in 715 family members with DNA available. We studied the enrichment of variants previously implicated with monogenic dyslipidemias and/or lipid levels in the general population by comparing allele frequencies between the FCH families and population samples. We also constructed weighted polygenic scores using 212 lipid-associated SNPs and estimated the relative contributions of Mendelian variants and polygenic scores to the risk of FCH in the families. We identified, across the whole allele frequency spectrum, an enrichment of variants known to elevate, and a deficiency of variants known to lower LDL-C and/or TG levels among both probands and affected FCH individuals. The score based on TG associated SNPs was particularly high among affected individuals compared to non-affected family members. Out of 234 affected FCH individuals across the families, seven (3%) carried Mendelian variants and 83 (35%) showed high accumulation of either known LDL-C or TG elevating variants by having either polygenic score over the 90th percentile in the population. The positive predictive value of high score was much higher for affected FCH individuals than for similar sporadic cases in the population. FCH is highly polygenic, supporting the hypothesis that variants across the whole allele frequency spectrum contribute to this complex familial trait. Polygenic SNP panels improve identification of individuals affected with FCH, but their clinical utility remains to be defined.

2 Article Discovery and refinement of loci associated with lipid levels. 2013

Willer, Cristen J / Schmidt, Ellen M / Sengupta, Sebanti / Peloso, Gina M / Gustafsson, Stefan / Kanoni, Stavroula / Ganna, Andrea / Chen, Jin / Buchkovich, Martin L / Mora, Samia / Beckmann, Jacques S / Bragg-Gresham, Jennifer L / Chang, Hsing-Yi / Demirkan, Ayşe / Den Hertog, Heleen M / Do, Ron / Donnelly, Louise A / Ehret, Georg B / Esko, Tõnu / Feitosa, Mary F / Ferreira, Teresa / Fischer, Krista / Fontanillas, Pierre / Fraser, Ross M / Freitag, Daniel F / Gurdasani, Deepti / Heikkilä, Kauko / Hyppönen, Elina / Isaacs, Aaron / Jackson, Anne U / Johansson, Åsa / Johnson, Toby / Kaakinen, Marika / Kettunen, Johannes / Kleber, Marcus E / Li, Xiaohui / Luan, Jian'an / Lyytikäinen, Leo-Pekka / Magnusson, Patrik K E / Mangino, Massimo / Mihailov, Evelin / Montasser, May E / Müller-Nurasyid, Martina / Nolte, Ilja M / O'Connell, Jeffrey R / Palmer, Cameron D / Perola, Markus / Petersen, Ann-Kristin / Sanna, Serena / Saxena, Richa / Service, Susan K / Shah, Sonia / Shungin, Dmitry / Sidore, Carlo / Song, Ci / Strawbridge, Rona J / Surakka, Ida / Tanaka, Toshiko / Teslovich, Tanya M / Thorleifsson, Gudmar / Van den Herik, Evita G / Voight, Benjamin F / Volcik, Kelly A / Waite, Lindsay L / Wong, Andrew / Wu, Ying / Zhang, Weihua / Absher, Devin / Asiki, Gershim / Barroso, Inês / Been, Latonya F / Bolton, Jennifer L / Bonnycastle, Lori L / Brambilla, Paolo / Burnett, Mary S / Cesana, Giancarlo / Dimitriou, Maria / Doney, Alex S F / Döring, Angela / Elliott, Paul / Epstein, Stephen E / Ingi Eyjolfsson, Gudmundur / Gigante, Bruna / Goodarzi, Mark O / Grallert, Harald / Gravito, Martha L / Groves, Christopher J / Hallmans, Göran / Hartikainen, Anna-Liisa / Hayward, Caroline / Hernandez, Dena / Hicks, Andrew A / Holm, Hilma / Hung, Yi-Jen / Illig, Thomas / Jones, Michelle R / Kaleebu, Pontiano / Kastelein, John J P / Khaw, Kay-Tee / Kim, Eric / Klopp, Norman / Komulainen, Pirjo / Kumari, Meena / Langenberg, Claudia / Lehtimäki, Terho / Lin, Shih-Yi / Lindström, Jaana / Loos, Ruth J F / Mach, François / McArdle, Wendy L / Meisinger, Christa / Mitchell, Braxton D / Müller, Gabrielle / Nagaraja, Ramaiah / Narisu, Narisu / Nieminen, Tuomo V M / Nsubuga, Rebecca N / Olafsson, Isleifur / Ong, Ken K / Palotie, Aarno / Papamarkou, Theodore / Pomilla, Cristina / Pouta, Anneli / Rader, Daniel J / Reilly, Muredach P / Ridker, Paul M / Rivadeneira, Fernando / Rudan, Igor / Ruokonen, Aimo / Samani, Nilesh / Scharnagl, Hubert / Seeley, Janet / Silander, Kaisa / Stančáková, Alena / Stirrups, Kathleen / Swift, Amy J / Tiret, Laurence / Uitterlinden, Andre G / van Pelt, L Joost / Vedantam, Sailaja / Wainwright, Nicholas / Wijmenga, Cisca / Wild, Sarah H / Willemsen, Gonneke / Wilsgaard, Tom / Wilson, James F / Young, Elizabeth H / Zhao, Jing Hua / Adair, Linda S / Arveiler, Dominique / Assimes, Themistocles L / Bandinelli, Stefania / Bennett, Franklyn / Bochud, Murielle / Boehm, Bernhard O / Boomsma, Dorret I / Borecki, Ingrid B / Bornstein, Stefan R / Bovet, Pascal / Burnier, Michel / Campbell, Harry / Chakravarti, Aravinda / Chambers, John C / Chen, Yii-Der Ida / Collins, Francis S / Cooper, Richard S / Danesh, John / Dedoussis, George / de Faire, Ulf / Feranil, Alan B / Ferrières, Jean / Ferrucci, Luigi / Freimer, Nelson B / Gieger, Christian / Groop, Leif C / Gudnason, Vilmundur / Gyllensten, Ulf / Hamsten, Anders / Harris, Tamara B / Hingorani, Aroon / Hirschhorn, Joel N / Hofman, Albert / Hovingh, G Kees / Hsiung, Chao Agnes / Humphries, Steve E / Hunt, Steven C / Hveem, Kristian / Iribarren, Carlos / Järvelin, Marjo-Riitta / Jula, Antti / Kähönen, Mika / Kaprio, Jaakko / Kesäniemi, Antero / Kivimaki, Mika / Kooner, Jaspal S / Koudstaal, Peter J / Krauss, Ronald M / Kuh, Diana / Kuusisto, Johanna / Kyvik, Kirsten O / Laakso, Markku / Lakka, Timo A / Lind, Lars / Lindgren, Cecilia M / Martin, Nicholas G / März, Winfried / McCarthy, Mark I / McKenzie, Colin A / Meneton, Pierre / Metspalu, Andres / Moilanen, Leena / Morris, Andrew D / Munroe, Patricia B / Njølstad, Inger / Pedersen, Nancy L / Power, Chris / Pramstaller, Peter P / Price, Jackie F / Psaty, Bruce M / Quertermous, Thomas / Rauramaa, Rainer / Saleheen, Danish / Salomaa, Veikko / Sanghera, Dharambir K / Saramies, Jouko / Schwarz, Peter E H / Sheu, Wayne H-H / Shuldiner, Alan R / Siegbahn, Agneta / Spector, Tim D / Stefansson, Kari / Strachan, David P / Tayo, Bamidele O / Tremoli, Elena / Tuomilehto, Jaakko / Uusitupa, Matti / van Duijn, Cornelia M / Vollenweider, Peter / Wallentin, Lars / Wareham, Nicholas J / Whitfield, John B / Wolffenbuttel, Bruce H R / Ordovas, Jose M / Boerwinkle, Eric / Palmer, Colin N A / Thorsteinsdottir, Unnur / Chasman, Daniel I / Rotter, Jerome I / Franks, Paul W / Ripatti, Samuli / Cupples, L Adrienne / Sandhu, Manjinder S / Rich, Stephen S / Boehnke, Michael / Deloukas, Panos / Kathiresan, Sekar / Mohlke, Karen L / Ingelsson, Erik / Abecasis, Gonçalo R / Anonymous3140771. ·Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA. · Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA. · Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA. · Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA. · Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA. · Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. · Broad Institute, Program in Medical and Population Genetics, Cambridge, Massachusetts 02142, USA. · Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, Sweden. · Science for Life Laboratory, Uppsala University, Uppsala, Sweden. · Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, CB10 1SA, Hinxton, United Kingdom. · Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. · Department of Genetics, University of North Carolina, Chapel Hill, NC 27599 USA. · Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Ave., Boston MA 02215, USA. · Harvard Medical School, Boston MA 02115, USA. · Service of Medical Genetics, Lausanne University Hospital, Lausanne, Switzerland. · Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland. · Division of Preventive Medicine and Health Services Research, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan. · Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands. · Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands. · Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School. Dundee, DD1 9SY, United Kingdom. · Cardiology, Department of Specialities of Medicine, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, 1211 Geneva 14, Switzerland. · Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. · Estonian Genome Center of the University of Tartu, Tartu, Estonia. · Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia. · Department of Genetics, Washington University School of Medicine, USA. · Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom. · Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland, United Kingdom. · Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. · Hjelt Institute, Department of Public Health, University of Helsinki, Finland. · Centre For Paediatric Epidemiology and Biostatistics/MRC Centre of Epidemiology for Child Health, University College of London Institute of Child Health, London, United Kingdom. · Centre for Medical Systems Biology, Leiden, the Netherlands. · Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. · Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden. · Genome Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. · Clinical Pharmacology, NIHR Cardiovascular Biomedical Research Unit, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry Queen Mary University of London, London, UK. · Biocenter Oulu, University of Oulu, Oulu, Finland. · Institute of Health Sciences, University of Oulu, Finland. · Institute for Molecular Medicine Finland FIMM, University of Helsinki, Finland. · Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland. · Department of Internal Medicine II - Cardiology, University of Ulm Medical Centre, Ulm, Germany. · Mannheim Institute of Public Health, Social and Preventive Medicine, Medical Faculty of Mannheim, University of Heidelberg, Ludolf-Krehl-Strasse 7-11, 68167 Mannheim, Germany. · Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. · MRC Epidemiology Unit, Institute of Metabolic Science, Box 285, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, United Kingdom. · Department of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland. · Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere 33014, Finland. · Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom. · Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland, School of Medicine, Baltimore, Maryland. · Institute of Genetic Epidemiology, Helmholtz Zentrum München, Neuherberg 85764, Germany. · Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians University, Munich, Germany. · Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University of Munich, Munich, Germany. · Department of Epidemiology, University of Groningen, University Medical Center Groningen, The Netherlands. · Division of Endocrinology, Children's Hospital Boston, Massachusetts 02115, USA. · Division of Genetics, Program in Genomics, Children's Hospital, Boston, Massachusetts 02115, USA. · Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato, 09042, Italy. · Massachusetts General Hospital/Broad Institute, Harvard University, Cambridge, MA, USA. · Center for Neurobehavioral Genetics, The Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, USA. · Genetic Epidemiology Group, Deparment of Epidemiology and Public Health, UCL, London WC1E 6BT, United Kingdom. · Department of Clinical Sciences, Genetic & Molecular Epidemiology Unit, Lund University Diabetes Center, Scania University Hosptial, Malmö, Sweden. · Department of Odontology, Umeå University, Umeå, Sweden. · Department of Public Health and Primary Care, Unit of Medicine, Umeå University, Umeå, Sweden. · Dipartimento di Scienze Biomediche, Universita di Sassari, 07100 SS, Italy. · Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden. · Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden. · Clinical Research Branch, National Institute Health, Baltimore, MD, USA. · deCODE Genetics/Amgen, 101 Reykjavik, Iceland. · Department of Genetics, University of Pennsylvania - School of Medicine, Philadelphia PA, 19104, USA. · Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania - School of Medicine, Philadelphia PA, 19104, USA. · Human Genetics Center, University of Texas Health Science Center - School of Public Health, Houston, TX 77030, USA. · HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA. · MRC Unit for Lifelong Health and Ageing, 33 Bedford Place, London, WC1B 5JU, United Kingdom. · Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. · Ealing Hospital, Southall, Middlesex UB1 3HW, United Kingdom. · MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda. · University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Level 4, Institute of Metabolic Science Box 289 Addenbrooke's Hospital Cambridge CB2 OQQ, UK. · Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. · Genome Technology Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA. · Department of Experimental Medicine, University of Milano Bicocca, Italy. · MedStar Health Research Institute, 6525 Belcrest Road, Suite 700, Hyattsville, MD 20782, USA. · Research Centre on Public Health, University of Milano Bicocca, Italy. · Department of Dietetics-Nutrition, Harokopio University, 70 El. Venizelou Str, Athens, Greece. · Institute of Epidemiology I, Helmholtz Zentrum München, Neuherberg 85764, Germany. · Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg 85764, Germany. · Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, UK. · The Laboratory in Mjodd, 108 Reykjavik, Iceland. · Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. · Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. · Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg 85764, Germany. · Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, OX3 7LJ, United Kingdom. · Department of Public Health and Clinical Medicine, Nutritional research, Umeå University, Umeå, Sweden. · Department of Clinical Sciences/Obstetrics and Gynecology, Oulu University Hospital, Oulu, Finland. · MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland, United Kingdom. · Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA. · Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy - Affiliated Institute of the University of Lübeck, Lübeck, Germany. · Division of Endocrinology & Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. · Hannover Unified Biobank, Hannover Medical School, Hannover 30625, Germany. · Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. · Clinical Gerontology Unit, University of Cambridge, Cambridge, United Kingdom. · Kuopio Research Institute of Exercise Medicine, Kuopio, Finland. · Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, School of Medicine, National Yang-Ming University, Taipei, Taiwan. · Diabetes Prevention Unit, National Institute for Health and Welfare, 00271 Helsinki, Finland. · The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, USA. · The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at ount Sinai, New York, USA. · The Mindich Child Health and Development Institute, The Icahn School of Medicine at Mount Sinai, New York. · School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, United Kingdom. · Institute for Medical Informatics and Biometrics, University of Dresden, Medical Faculty Carl Gustav Carus, Fetscherstrasse 74, 01307 Dresden, Germany. · Laboratory of Genetics, National Institute on Aging, Baltimore, MD21224, USA. · Department of Clinical Pharmacology, University of Tampere School of Medicine, Tamperew 33014, Finland. · Department of Internal Medicine, Päijät-Häme Central Hospital, Lahti, Finland. · Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland. · Department of Clinical Biochemistry, Landspitali University Hospital, 101 Reykjavik, Iceland. · Department of Medical Genetics, Haartman Institute, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. · Genetic Epidemiology Group, Wellcome Trust Sanger Institute, Hinxton, Cambridge, United ingdom. · Department of Statistical Sciences, University College of London, London, United Kingdom. · National Institute for Health and Welfare, Oulu, Finland. · Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Blvd, Building 421, Translational Research Center, Philadelphia, PA 19104-5158, USA. · Division of Translational Medicine and Human Genetics, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Blvd, Building 421, Translational Research Center, Philadelphia, PA 19104-5158, USA. · Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands. · Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands. · Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging NCHA), Leiden, The Netherlands. · Department of Clinical Sciences/Clinical Chemistry, University of Oulu, Oulu, Finland. · National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, UK. · Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, LE3 9QP, UK. · Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria. · School of International Development, University of East Anglia, Norwich NR4 7TJ, United Kingdom. · University of Eastern Finland and Kuopio University Hospital, 70210 Kuopio, Finland. · INSERM UMRS 937, Pierre and Marie Curie University, Paris, France. · Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, The Netherlands. · LifeLines Cohort Study, University of Groningen, University Medical Center Groningen, The Netherlands. · Department of Genetics, University of Groningen, University Medical Center Groningen, The Netherlands. · Department of Biological Psychology, VU Univ, Amsterdam, The Netherlands. · Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway. · Department of Nutrition, University of North Carolina, Chapel Hill, NC, USA. · Department of Epidemiology and Public Health, EA 3430, University of Strasbourg, Faculty of Medicine, Strasbourg, France. · Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA. · Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy. · Chemical Pathology, Department of Pathology, University of the West Indies, Mona, Kingston 7, Jamaica. · Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Route de la Corniche 10, 1010 Lausanne, Switzerland. · Division of Endocrinology and Diabetes, Department of Internal Medicine, Ulm University Medical Centre, Ulm, Germany. · Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore. · Department of Medicine III, University of Dresden, Medical Faculty Carl Gustav Carus, Fetscherstrasse 74, 01307 Dresden, Germany. · Ministry of Health, Victoria, Republic of Seychelles. · Service of Nephrology, Lausanne University Hospital, Lausanne, Switzerland. · Imperial College Healthcare NHS Trust, London, United Kingdom. · Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California, USA. · Department of Medicine, University of California Los Angeles, Los Angeles, California, USA. · Department of Preventive Medicine and Epidemiology, Loyola University Medical School, Maywood, Illinois 60153, USA. · Office of Population Studies Foundation, University of San Carlos, Talamban, Cebu City, Philippines. · Department of Cardiology, Toulouse University School of Medicine, Rangueil Hospital, Toulouse, France. · Department of Psychiatry, University of California, Los Angeles, USA. · Department of Clinical Sciences, Lund University, SE-20502, Malmö, Sweden. · Department of Medicine, Helsinki University Hospital, FI-00029 Helsinki, Finland. · Icelandic Heart Association, Kopavogur, Iceland. · Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden. · Laboratory of Epidemiology, Demography, and Biometry, National Institute on Ageing, Bethesda, MD, USA. · Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan. · Cardiovascular Genetics, BHF Laboratories, Institute Cardiovascular Science, University College London, London, United Kingdom. · Cardiovascular Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA. · HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway. · Kaiser Permanente, Division of Research, Oakland, CA, USA. · Unit of Primary Care, Oulu University Hospital, Oulu, Finland. · Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland. · Department of Clinical Physiology, University of Tampere School of Medicine, Tampere 33014, Finland. · Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland. · Institute of Clinical Medicine, Department of Medicine, University of Oulu and Clinical Research Center, Oulu University Hospital, Oulu, Finland. · National Heart & Lung Institute, Imperial College London, Hammersmith Hospital, London, United Kingdom. · Children's Hospital Oakland Research Institute, 5700 Martin Luther King Junior Way, Oakland, CA 94609, USA. · Department of Medicine, University of Eastern Finland and Kuopio University Hospital, 70210 Kuopio, Finland. · Institute of Regional Health Services Research, University of Southern Denmark, Odense, Denmark. · Odense Patient data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark. · Institute of Biomedicine/Physiology, University of Eastern Finland, Kuopio Campus, Finland. · Department of Medical Sciences, Uppsala University, Uppsala, Sweden. · Queensland Institute of Medical Research, Locked Bag 2000, Royal Brisbane Hospital, Queensland 4029, Australia. · Synlab Academy, Synlab Services GmbH,Gottlieb-Daimler-Straße 25, 68165 Mannheim, Germany. · Tropical Metabolism Research Unit, Tropical Medicine Research Institute, University of the West Indies, Mona, Kingston 7, Jamaica. · U872 Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, 75006 Paris, France. · Department of Medicine, Kuopio University Hospital, Kuopio, Finland. · Department of Neurology, General Central Hospital, Bolzano, Italy. · Department of Neurology, University of Lübeck, Lübeck, Germany. · Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, USA. · Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA. · Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland. · Center for Non-Communicable Diseases, Karachi, Pakistan. · Department of Medicine, University of Pennsylvania, USA. · Unit of Chronic Disease Epidemiology and Prevention, National Institute for Health and Welfare, Helsinki, Finland. · South Karelia Central Hospital, Lappeenranta, Finland. · Paul Langerhans Institute Dresden, German Center for Diabetes Research (DZD), Dresden, Germany. · Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan. · Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, Maryland. · Faculty of Medicine, University of Iceland, 101 Reykjavík, Iceland. · Division of Population Health Sciences and Education, St George's, University of London, Cranmer Terrace, London SW17 0RE, United Kingdom. · Department of Pharmacological Sciences, University of Milan, Monzino Cardiology Center, IRCCS, Milan, Italy. · Centre for Vascular Prevention, Danube-University Krems, 3500 Krems, Austria. · King Abdulaziz University, Faculty of Medicine, Jeddah 21589, Saudi Arabia. · Red RECAVA Grupo RD06/0014/0015, Hospital Universitario La Paz, 28046. · Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Finland. · Research Unit, Kuopio University Hospital, Kuopio, Finland. · Department of Medicine, Lausanne University Hospital, Switzerland. · Department of Endocrinology, University of Groningen, University Medical Center Groningen, The Netherlands. · Department of Cardiovascular Epidemiology and Population Genetics, National Center for rdiovascular Investigation, Madrid, Spain. · IMDEA-Alimentacion, Madrid, Spain. · Nutrition and Genomics Laboratory, Jean Mayer-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA. · Department of Nutrition, Harvard School of Public Health, Boston, MA, USA. · Framingham Heart Study, Framingham, MA, USA. · Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA. · Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. · Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA. ·Nat Genet · Pubmed #24097068.

ABSTRACT: Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 × 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.

3 Article Common variants associated with plasma triglycerides and risk for coronary artery disease. 2013

Do, Ron / Willer, Cristen J / Schmidt, Ellen M / Sengupta, Sebanti / Gao, Chi / Peloso, Gina M / Gustafsson, Stefan / Kanoni, Stavroula / Ganna, Andrea / Chen, Jin / Buchkovich, Martin L / Mora, Samia / Beckmann, Jacques S / Bragg-Gresham, Jennifer L / Chang, Hsing-Yi / Demirkan, Ayşe / Den Hertog, Heleen M / Donnelly, Louise A / Ehret, Georg B / Esko, Tõnu / Feitosa, Mary F / Ferreira, Teresa / Fischer, Krista / Fontanillas, Pierre / Fraser, Ross M / Freitag, Daniel F / Gurdasani, Deepti / Heikkilä, Kauko / Hyppönen, Elina / Isaacs, Aaron / Jackson, Anne U / Johansson, Asa / Johnson, Toby / Kaakinen, Marika / Kettunen, Johannes / Kleber, Marcus E / Li, Xiaohui / Luan, Jian'an / Lyytikäinen, Leo-Pekka / Magnusson, Patrik K E / Mangino, Massimo / Mihailov, Evelin / Montasser, May E / Müller-Nurasyid, Martina / Nolte, Ilja M / O'Connell, Jeffrey R / Palmer, Cameron D / Perola, Markus / Petersen, Ann-Kristin / Sanna, Serena / Saxena, Richa / Service, Susan K / Shah, Sonia / Shungin, Dmitry / Sidore, Carlo / Song, Ci / Strawbridge, Rona J / Surakka, Ida / Tanaka, Toshiko / Teslovich, Tanya M / Thorleifsson, Gudmar / Van den Herik, Evita G / Voight, Benjamin F / Volcik, Kelly A / Waite, Lindsay L / Wong, Andrew / Wu, Ying / Zhang, Weihua / Absher, Devin / Asiki, Gershim / Barroso, Inês / Been, Latonya F / Bolton, Jennifer L / Bonnycastle, Lori L / Brambilla, Paolo / Burnett, Mary S / Cesana, Giancarlo / Dimitriou, Maria / Doney, Alex S F / Döring, Angela / Elliott, Paul / Epstein, Stephen E / Eyjolfsson, Gudmundur Ingi / Gigante, Bruna / Goodarzi, Mark O / Grallert, Harald / Gravito, Martha L / Groves, Christopher J / Hallmans, Göran / Hartikainen, Anna-Liisa / Hayward, Caroline / Hernandez, Dena / Hicks, Andrew A / Holm, Hilma / Hung, Yi-Jen / Illig, Thomas / Jones, Michelle R / Kaleebu, Pontiano / Kastelein, John J P / Khaw, Kay-Tee / Kim, Eric / Klopp, Norman / Komulainen, Pirjo / Kumari, Meena / Langenberg, Claudia / Lehtimäki, Terho / Lin, Shih-Yi / Lindström, Jaana / Loos, Ruth J F / Mach, François / McArdle, Wendy L / Meisinger, Christa / Mitchell, Braxton D / Müller, Gabrielle / Nagaraja, Ramaiah / Narisu, Narisu / Nieminen, Tuomo V M / Nsubuga, Rebecca N / Olafsson, Isleifur / Ong, Ken K / Palotie, Aarno / Papamarkou, Theodore / Pomilla, Cristina / Pouta, Anneli / Rader, Daniel J / Reilly, Muredach P / Ridker, Paul M / Rivadeneira, Fernando / Rudan, Igor / Ruokonen, Aimo / Samani, Nilesh / Scharnagl, Hubert / Seeley, Janet / Silander, Kaisa / Stančáková, Alena / Stirrups, Kathleen / Swift, Amy J / Tiret, Laurence / Uitterlinden, Andre G / van Pelt, L Joost / Vedantam, Sailaja / Wainwright, Nicholas / Wijmenga, Cisca / Wild, Sarah H / Willemsen, Gonneke / Wilsgaard, Tom / Wilson, James F / Young, Elizabeth H / Zhao, Jing Hua / Adair, Linda S / Arveiler, Dominique / Assimes, Themistocles L / Bandinelli, Stefania / Bennett, Franklyn / Bochud, Murielle / Boehm, Bernhard O / Boomsma, Dorret I / Borecki, Ingrid B / Bornstein, Stefan R / Bovet, Pascal / Burnier, Michel / Campbell, Harry / Chakravarti, Aravinda / Chambers, John C / Chen, Yii-Der Ida / Collins, Francis S / Cooper, Richard S / Danesh, John / Dedoussis, George / de Faire, Ulf / Feranil, Alan B / Ferrières, Jean / Ferrucci, Luigi / Freimer, Nelson B / Gieger, Christian / Groop, Leif C / Gudnason, Vilmundur / Gyllensten, Ulf / Hamsten, Anders / Harris, Tamara B / Hingorani, Aroon / Hirschhorn, Joel N / Hofman, Albert / Hovingh, G Kees / Hsiung, Chao Agnes / Humphries, Steve E / Hunt, Steven C / Hveem, Kristian / Iribarren, Carlos / Järvelin, Marjo-Riitta / Jula, Antti / Kähönen, Mika / Kaprio, Jaakko / Kesäniemi, Antero / Kivimaki, Mika / Kooner, Jaspal S / Koudstaal, Peter J / Krauss, Ronald M / Kuh, Diana / Kuusisto, Johanna / Kyvik, Kirsten O / Laakso, Markku / Lakka, Timo A / Lind, Lars / Lindgren, Cecilia M / Martin, Nicholas G / März, Winfried / McCarthy, Mark I / McKenzie, Colin A / Meneton, Pierre / Metspalu, Andres / Moilanen, Leena / Morris, Andrew D / Munroe, Patricia B / Njølstad, Inger / Pedersen, Nancy L / Power, Chris / Pramstaller, Peter P / Price, Jackie F / Psaty, Bruce M / Quertermous, Thomas / Rauramaa, Rainer / Saleheen, Danish / Salomaa, Veikko / Sanghera, Dharambir K / Saramies, Jouko / Schwarz, Peter E H / Sheu, Wayne H-H / Shuldiner, Alan R / Siegbahn, Agneta / Spector, Tim D / Stefansson, Kari / Strachan, David P / Tayo, Bamidele O / Tremoli, Elena / Tuomilehto, Jaakko / Uusitupa, Matti / van Duijn, Cornelia M / Vollenweider, Peter / Wallentin, Lars / Wareham, Nicholas J / Whitfield, John B / Wolffenbuttel, Bruce H R / Altshuler, David / Ordovas, Jose M / Boerwinkle, Eric / Palmer, Colin N A / Thorsteinsdottir, Unnur / Chasman, Daniel I / Rotter, Jerome I / Franks, Paul W / Ripatti, Samuli / Cupples, L Adrienne / Sandhu, Manjinder S / Rich, Stephen S / Boehnke, Michael / Deloukas, Panos / Mohlke, Karen L / Ingelsson, Erik / Abecasis, Goncalo R / Daly, Mark J / Neale, Benjamin M / Kathiresan, Sekar. ·1] Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA. [2] Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA. [3] Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA. [4] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA. ·Nat Genet · Pubmed #24097064.

ABSTRACT: Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 × 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.

4 Article Genomic, transcriptomic, and lipidomic profiling highlights the role of inflammation in individuals with low high-density lipoprotein cholesterol. 2013

Laurila, Pirkka-Pekka / Surakka, Ida / Sarin, Antti-Pekka / Yetukuri, Laxman / Hyötyläinen, Tuulia / Söderlund, Sanni / Naukkarinen, Jussi / Tang, Jing / Kettunen, Johannes / Mirel, Daniel B / Soronen, Jarkko / Lehtimäki, Terho / Ruokonen, Aimo / Ehnholm, Christian / Eriksson, Johan G / Salomaa, Veikko / Jula, Antti / Raitakari, Olli T / Järvelin, Marjo-Riitta / Palotie, Aarno / Peltonen, Leena / Oresic, Matej / Jauhiainen, Matti / Taskinen, Marja-Riitta / Ripatti, Samuli. ·Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Finland. ·Arterioscler Thromb Vasc Biol · Pubmed #23413431.

ABSTRACT: OBJECTIVE: Low high-density lipoprotein cholesterol (HDL-C) is associated with cardiometabolic pathologies. In this study, we investigate the biological pathways and individual genes behind low HDL-C by integrating results from 3 high-throughput data sources: adipose tissue transcriptomics, HDL lipidomics, and dense marker genotypes from Finnish individuals with low or high HDL-C (n=450). APPROACH AND RESULTS: In the pathway analysis of genetic data, we demonstrate that genetic variants within inflammatory pathways were enriched among low HDL-C associated single-nucleotide polymorphisms, and the expression of these pathways upregulated in the adipose tissue of low HDL-C subjects. The lipidomic analysis highlighted the change in HDL particle quality toward putatively more inflammatory and less vasoprotective state in subjects with low HDL-C, as evidenced by their decreased antioxidative plasmalogen contents. We show that the focal point of these inflammatory pathways seems to be the HLA region with its low HDL-associated alleles also associating with more abundant local transcript levels in adipose tissue, increased plasma vascular cell adhesion molecule 1 (VCAM1) levels, and decreased HDL particle plasmalogen contents, markers of adipose tissue inflammation, vascular inflammation, and HDL antioxidative potential, respectively. In a population-based look-up of the inflammatory pathway single-nucleotide polymorphisms in a large Finnish cohorts (n=11 211), no association of the HLA region was detected for HDL-C as quantitative trait, but with extreme HDL-C phenotypes, implying the presence of low or high HDL genes in addition to the population-genomewide association studies-identified HDL genes. CONCLUSIONS: Our study highlights the role of inflammation with a genetic component in subjects with low HDL-C and identifies novel cis-expression quantitative trait loci (cis-eQTL) variants in HLA region to be associated with low HDL-C.

5 Article Genetic variants influencing circulating lipid levels and risk of coronary artery disease. 2010

Waterworth, Dawn M / Ricketts, Sally L / Song, Kijoung / Chen, Li / Zhao, Jing Hua / Ripatti, Samuli / Aulchenko, Yurii S / Zhang, Weihua / Yuan, Xin / Lim, Noha / Luan, Jian'an / Ashford, Sofie / Wheeler, Eleanor / Young, Elizabeth H / Hadley, David / Thompson, John R / Braund, Peter S / Johnson, Toby / Struchalin, Maksim / Surakka, Ida / Luben, Robert / Khaw, Kay-Tee / Rodwell, Sheila A / Loos, Ruth J F / Boekholdt, S Matthijs / Inouye, Michael / Deloukas, Panagiotis / Elliott, Paul / Schlessinger, David / Sanna, Serena / Scuteri, Angelo / Jackson, Anne / Mohlke, Karen L / Tuomilehto, Jaako / Roberts, Robert / Stewart, Alexandre / Kesäniemi, Y Antero / Mahley, Robert W / Grundy, Scott M / Anonymous1770673 / McArdle, Wendy / Cardon, Lon / Waeber, Gérard / Vollenweider, Peter / Chambers, John C / Boehnke, Michael / Abecasis, Gonçalo R / Salomaa, Veikko / Järvelin, Marjo-Riitta / Ruokonen, Aimo / Barroso, Inês / Epstein, Stephen E / Hakonarson, Hakon H / Rader, Daniel J / Reilly, Muredach P / Witteman, Jacqueline C M / Hall, Alistair S / Samani, Nilesh J / Strachan, David P / Barter, Philip / van Duijn, Cornelia M / Kooner, Jaspal S / Peltonen, Leena / Wareham, Nicholas J / McPherson, Ruth / Mooser, Vincent / Sandhu, Manjinder S. ·Genetics Division, GlaxoSmithKline R&D, King of Prussia, PA, USA. ·Arterioscler Thromb Vasc Biol · Pubmed #20864672.

ABSTRACT: OBJECTIVE: Genetic studies might provide new insights into the biological mechanisms underlying lipid metabolism and risk of CAD. We therefore conducted a genome-wide association study to identify novel genetic determinants of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. METHODS AND RESULTS: We combined genome-wide association data from 8 studies, comprising up to 17 723 participants with information on circulating lipid concentrations. We did independent replication studies in up to 37 774 participants from 8 populations and also in a population of Indian Asian descent. We also assessed the association between single-nucleotide polymorphisms (SNPs) at lipid loci and risk of CAD in up to 9 633 cases and 38 684 controls. We identified 4 novel genetic loci that showed reproducible associations with lipids (probability values, 1.6×10(-8) to 3.1×10(-10)). These include a potentially functional SNP in the SLC39A8 gene for HDL-C, an SNP near the MYLIP/GMPR and PPP1R3B genes for LDL-C, and at the AFF1 gene for triglycerides. SNPs showing strong statistical association with 1 or more lipid traits at the CELSR2, APOB, APOE-C1-C4-C2 cluster, LPL, ZNF259-APOA5-A4-C3-A1 cluster and TRIB1 loci were also associated with CAD risk (probability values, 1.1×10(-3) to 1.2×10(-9)). CONCLUSIONS: We have identified 4 novel loci associated with circulating lipids. We also show that in addition to those that are largely associated with LDL-C, genetic loci mainly associated with circulating triglycerides and HDL-C are also associated with risk of CAD. These findings potentially provide new insights into the biological mechanisms underlying lipid metabolism and CAD risk.

6 Article Biological, clinical and population relevance of 95 loci for blood lipids. 2010

Teslovich, Tanya M / Musunuru, Kiran / Smith, Albert V / Edmondson, Andrew C / Stylianou, Ioannis M / Koseki, Masahiro / Pirruccello, James P / Ripatti, Samuli / Chasman, Daniel I / Willer, Cristen J / Johansen, Christopher T / Fouchier, Sigrid W / Isaacs, Aaron / Peloso, Gina M / Barbalic, Maja / Ricketts, Sally L / Bis, Joshua C / Aulchenko, Yurii S / Thorleifsson, Gudmar / Feitosa, Mary F / Chambers, John / Orho-Melander, Marju / Melander, Olle / Johnson, Toby / Li, Xiaohui / Guo, Xiuqing / Li, Mingyao / Shin Cho, Yoon / Jin Go, Min / Jin Kim, Young / Lee, Jong-Young / Park, Taesung / Kim, Kyunga / Sim, Xueling / Twee-Hee Ong, Rick / Croteau-Chonka, Damien C / Lange, Leslie A / Smith, Joshua D / Song, Kijoung / Hua Zhao, Jing / Yuan, Xin / Luan, Jian'an / Lamina, Claudia / Ziegler, Andreas / Zhang, Weihua / Zee, Robert Y L / Wright, Alan F / Witteman, Jacqueline C M / Wilson, James F / Willemsen, Gonneke / Wichmann, H-Erich / Whitfield, John B / Waterworth, Dawn M / Wareham, Nicholas J / Waeber, Gérard / Vollenweider, Peter / Voight, Benjamin F / Vitart, Veronique / Uitterlinden, Andre G / Uda, Manuela / Tuomilehto, Jaakko / Thompson, John R / Tanaka, Toshiko / Surakka, Ida / Stringham, Heather M / Spector, Tim D / Soranzo, Nicole / Smit, Johannes H / Sinisalo, Juha / Silander, Kaisa / Sijbrands, Eric J G / Scuteri, Angelo / Scott, James / Schlessinger, David / Sanna, Serena / Salomaa, Veikko / Saharinen, Juha / Sabatti, Chiara / Ruokonen, Aimo / Rudan, Igor / Rose, Lynda M / Roberts, Robert / Rieder, Mark / Psaty, Bruce M / Pramstaller, Peter P / Pichler, Irene / Perola, Markus / Penninx, Brenda W J H / Pedersen, Nancy L / Pattaro, Cristian / Parker, Alex N / Pare, Guillaume / Oostra, Ben A / O'Donnell, Christopher J / Nieminen, Markku S / Nickerson, Deborah A / Montgomery, Grant W / Meitinger, Thomas / McPherson, Ruth / McCarthy, Mark I / McArdle, Wendy / Masson, David / Martin, Nicholas G / Marroni, Fabio / Mangino, Massimo / Magnusson, Patrik K E / Lucas, Gavin / Luben, Robert / Loos, Ruth J F / Lokki, Marja-Liisa / Lettre, Guillaume / Langenberg, Claudia / Launer, Lenore J / Lakatta, Edward G / Laaksonen, Reijo / Kyvik, Kirsten O / Kronenberg, Florian / König, Inke R / Khaw, Kay-Tee / Kaprio, Jaakko / Kaplan, Lee M / Johansson, Asa / Jarvelin, Marjo-Riitta / Janssens, A Cecile J W / Ingelsson, Erik / Igl, Wilmar / Kees Hovingh, G / Hottenga, Jouke-Jan / Hofman, Albert / Hicks, Andrew A / Hengstenberg, Christian / Heid, Iris M / Hayward, Caroline / Havulinna, Aki S / Hastie, Nicholas D / Harris, Tamara B / Haritunians, Talin / Hall, Alistair S / Gyllensten, Ulf / Guiducci, Candace / Groop, Leif C / Gonzalez, Elena / Gieger, Christian / Freimer, Nelson B / Ferrucci, Luigi / Erdmann, Jeanette / Elliott, Paul / Ejebe, Kenechi G / Döring, Angela / Dominiczak, Anna F / Demissie, Serkalem / Deloukas, Panagiotis / de Geus, Eco J C / de Faire, Ulf / Crawford, Gabriel / Collins, Francis S / Chen, Yii-der I / Caulfield, Mark J / Campbell, Harry / Burtt, Noel P / Bonnycastle, Lori L / Boomsma, Dorret I / Boekholdt, S Matthijs / Bergman, Richard N / Barroso, Inês / Bandinelli, Stefania / Ballantyne, Christie M / Assimes, Themistocles L / Quertermous, Thomas / Altshuler, David / Seielstad, Mark / Wong, Tien Y / Tai, E-Shyong / Feranil, Alan B / Kuzawa, Christopher W / Adair, Linda S / Taylor, Herman A / Borecki, Ingrid B / Gabriel, Stacey B / Wilson, James G / Holm, Hilma / Thorsteinsdottir, Unnur / Gudnason, Vilmundur / Krauss, Ronald M / Mohlke, Karen L / Ordovas, Jose M / Munroe, Patricia B / Kooner, Jaspal S / Tall, Alan R / Hegele, Robert A / Kastelein, John J P / Schadt, Eric E / Rotter, Jerome I / Boerwinkle, Eric / Strachan, David P / Mooser, Vincent / Stefansson, Kari / Reilly, Muredach P / Samani, Nilesh J / Schunkert, Heribert / Cupples, L Adrienne / Sandhu, Manjinder S / Ridker, Paul M / Rader, Daniel J / van Duijn, Cornelia M / Peltonen, Leena / Abecasis, Gonçalo R / Boehnke, Michael / Kathiresan, Sekar. ·Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA. ·Nature · Pubmed #20686565.

ABSTRACT: Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.

7 Article A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium. 2009

Soranzo, Nicole / Spector, Tim D / Mangino, Massimo / Kühnel, Brigitte / Rendon, Augusto / Teumer, Alexander / Willenborg, Christina / Wright, Benjamin / Chen, Li / Li, Mingyao / Salo, Perttu / Voight, Benjamin F / Burns, Philippa / Laskowski, Roman A / Xue, Yali / Menzel, Stephan / Altshuler, David / Bradley, John R / Bumpstead, Suzannah / Burnett, Mary-Susan / Devaney, Joseph / Döring, Angela / Elosua, Roberto / Epstein, Stephen E / Erber, Wendy / Falchi, Mario / Garner, Stephen F / Ghori, Mohammed J R / Goodall, Alison H / Gwilliam, Rhian / Hakonarson, Hakon H / Hall, Alistair S / Hammond, Naomi / Hengstenberg, Christian / Illig, Thomas / König, Inke R / Knouff, Christopher W / McPherson, Ruth / Melander, Olle / Mooser, Vincent / Nauck, Matthias / Nieminen, Markku S / O'Donnell, Christopher J / Peltonen, Leena / Potter, Simon C / Prokisch, Holger / Rader, Daniel J / Rice, Catherine M / Roberts, Robert / Salomaa, Veikko / Sambrook, Jennifer / Schreiber, Stefan / Schunkert, Heribert / Schwartz, Stephen M / Serbanovic-Canic, Jovana / Sinisalo, Juha / Siscovick, David S / Stark, Klaus / Surakka, Ida / Stephens, Jonathan / Thompson, John R / Völker, Uwe / Völzke, Henry / Watkins, Nicholas A / Wells, George A / Wichmann, H-Erich / Van Heel, David A / Tyler-Smith, Chris / Thein, Swee Lay / Kathiresan, Sekar / Perola, Markus / Reilly, Muredach P / Stewart, Alexandre F R / Erdmann, Jeanette / Samani, Nilesh J / Meisinger, Christa / Greinacher, Andreas / Deloukas, Panos / Ouwehand, Willem H / Gieger, Christian. ·Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK. ns6@sanger.ac.uk ·Nat Genet · Pubmed #19820697.

ABSTRACT: The number and volume of cells in the blood affect a wide range of disorders including cancer and cardiovascular, metabolic, infectious and immune conditions. We consider here the genetic variation in eight clinically relevant hematological parameters, including hemoglobin levels, red and white blood cell counts and platelet counts and volume. We describe common variants within 22 genetic loci reproducibly associated with these hematological parameters in 13,943 samples from six European population-based studies, including 6 associated with red blood cell parameters, 15 associated with platelet parameters and 1 associated with total white blood cell count. We further identified a long-range haplotype at 12q24 associated with coronary artery disease and myocardial infarction in 9,479 cases and 10,527 controls. We show that this haplotype demonstrates extensive disease pleiotropy, as it contains known risk loci for type 1 diabetes, hypertension and celiac disease and has been spread by a selective sweep specific to European and geographically nearby populations.