Author: "Raitakari, O." / Publisher: nature publishing group - Searchworks@Jio Institute Digital Library Search Results

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1. Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson's disease

Author: Bryois J., Skene N. G., Hansen T. F., Kogelman L. J. A., Watson H. J., Liu Z., Adan R., Alfredsson L., Ando T., Andreassen O., Baker J., Bergen A., Berrettini W., Birgegard A., Boden J., Boehm I., Boni C., Boraska Perica V., Brandt H., Breen G., Buehren K., Bulik C., Burghardt R., Cassina M., Cichon S., Clementi M., Coleman J., Cone R., Courtet P., Crawford S., Crow S., Crowley J., Danner U., Davis O., de Zwaan M., Dedoussis G., Degortes D., DeSocio J., Dick D., Dikeos D., Dina C., Dmitrzak-Weglarz M., Docampo Martinez E., Duncan L., Egberts K., Ehrlich S., Escaramis G., Esko T., Estivill X., Farmer A., Favaro A., Fernandez-Aranda F., Fichter M., Fischer K., Focker M., Foretova L., Forstner A., Forzan M., Franklin C., Gallinger S., Gaspar H., Giegling I., Giuranna J., Giusti-Rodriquez P., Gonidakis F., Gordon S., Gorwood P., Gratacos Mayora M., Grove J., Guillaume S., Guo Y., Hakonarson H., Halmi K., Hanscombe K., Hatzikotoulas K., Hauser J., Hebebrand J., Helder S., Henders A., Herms S., Herpertz-Dahlmann B., Herzog W., Hinney A., Horwood L. J., Hubel C., Huckins L., Hudson J., Imgart H., Inoko H., Janout V., Jimenez-Murcia S., Johnson C., Jordan J., Julia A., Jureus A., Kalsi G., Kaminska D., Kaplan A., Kaprio J., Karhunen L., Karwautz A., Kas M., Kaye W., Kennedy J., Kennedy M., Keski-Rahkonen A., Kiezebrink K., Kim Y. -R., Kirk K., Klareskog L., Klump K., Knudsen G. P., La Via M., Landen M., Larsen J., Le Hellard S., Leppa V., Levitan R., Li D., Lichtenstein P., Lilenfeld L., Lin B. D., Lissowska J., Luykx J., Magistretti P., Maj M., Mannik K., Marsal S., Marshall C., Martin N., Mattheisen M., Mattingsdal M., McDevitt S., McGuffin P., Medland S., Metspalu A., Meulenbelt I., Micali N., Mitchell J., Mitchell K., Monteleone P., Monteleone A. M., Montgomery G., Mortensen P. B., Munn-Chernoff M., Nacmias B., Navratilova M., Norring C., Ntalla I., Olsen C., Ophoff R., O'Toole J., Padyukov L., Palotie A., Pantel J., Papezova H., Parker R., Pearson J., Pedersen N., Petersen L., Pinto D., Purves K., Rabionet R., Raevuori A., Ramoz N., Reichborn-Kjennerud T., Ricca V., Ripatti S., Ripke S., Ritschel F., Roberts M., Rotondo A., Rujescu D., Rybakowski F., Santonastaso P., Scherag A., Scherer S., Schmidt U., Schork N., Schosser A., Seitz J., Slachtova L., Slagboom P. E., Slof-Op 't Landt M., Slopien A., Sorbi S., Strober M., Stuber G., Sullivan P., Swiatkowska B., Szatkiewicz J., Tachmazidou I., Tenconi E., Thornton L., Tortorella A., Tozzi F., Treasure J., Tsitsika A., Tyszkiewicz-Nwafor M., Tziouvas K., van Elburg A., van Furth E., Wade T., Wagner G., Walton E., Watson H., Werge T., Whiteman D., Widen E., Woodside D. B., Yao S., Yilmaz Z., Zeggini E., Zerwas S., Zipfel S., Anttila V., Artto V., Belin A. C., de Boer I., Boomsma D. I., Borte S., Chasman D. I., Cherkas L., Christensen A. F., Cormand B., Cuenca-Leon E., Davey-Smith G., Dichgans M., van Duijn C., Esserlind A. L., Ferrari M., Frants R. R., Freilinger T., Furlotte N., Gormley P., Griffiths L., Hamalainen E., Hiekkala M., Ikram M. A., Ingason A., Jarvelin M. -R., Kajanne R., Kallela M., Kaunisto M., Kubisch C., Kurki M., Kurth T., Launer L., Lehtimaki T., Lessel D., Ligthart L., Litterman N., Maagdenberg A., Macaya A., Malik R., Mangino M., McMahon G., Muller-Myhsok B., Neale B. M., Northover C., Nyholt D. R., Olesen J., Palta P., Pedersen L., Posthuma D., Pozo-Rosich P., Pressman A., Raitakari O., Schurks M., Sintas C., Stefansson K., Stefansson H., Steinberg S., Strachan D., Terwindt G., Vila-Pueyo M., Wessman M., Winsvold B. S., Zhao H., Zwart J. A., Agee M., Alipanahi B., Auton A., Bell R., Bryc K., Elson S., Fontanillas P., Heilbron K., Hinds D., Huber K., Kleinman A., McCreight J., McIntyre M., Mountain J., Noblin E., Pitts S., Sathirapongsasuti J., Sazonova O., Shelton J., Shringarpure S., Tian C., Tung J., Vacic V., Wilson C., Brueggeman L., Bulik C. M., Arenas E., Hjerling-Leffler J., Sullivan P. F., Functional Genomics, APH - Methodology, APH - Mental Health, Biological Psychology, APH - Personalized Medicine, Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, Bryois, Julien, Hansen, Thomas Folkmann, Kogelman, Lisette J A, Watson, Hunna J, Breen, Gerome, Bulik, Cynthia M, Micali, Nadia, van Duijn, C, Kas lab, Bryois, J., Skene, N. G., Hansen, T. F., Kogelman, L. J. A., Watson, H. J., Liu, Z., Adan, R., Alfredsson, L., Ando, T., Andreassen, O., Baker, J., Bergen, A., Berrettini, W., Birgegard, A., Boden, J., Boehm, I., Boni, C., Boraska Perica, V., Brandt, H., Breen, G., Buehren, K., Bulik, C., Burghardt, R., Cassina, M., Cichon, S., Clementi, M., Coleman, J., Cone, R., Courtet, P., Crawford, S., Crow, S., Crowley, J., Danner, U., Davis, O., de Zwaan, M., Dedoussis, G., Degortes, D., Desocio, J., Dick, D., Dikeos, D., Dina, C., Dmitrzak-Weglarz, M., Docampo Martinez, E., Duncan, L., Egberts, K., Ehrlich, S., Escaramis, G., Esko, T., Estivill, X., Farmer, A., Favaro, A., Fernandez-Aranda, F., Fichter, M., Fischer, K., Focker, M., Foretova, L., Forstner, A., Forzan, M., Franklin, C., Gallinger, S., Gaspar, H., Giegling, I., Giuranna, J., Giusti-Rodriquez, P., Gonidakis, F., Gordon, S., Gorwood, P., Gratacos Mayora, M., Grove, J., Guillaume, S., Guo, Y., Hakonarson, H., Halmi, K., Hanscombe, K., Hatzikotoulas, K., Hauser, J., Hebebrand, J., Helder, S., Henders, A., Herms, S., Herpertz-Dahlmann, B., Herzog, W., Hinney, A., Horwood, L. J., Hubel, C., Huckins, L., Hudson, J., Imgart, H., Inoko, H., Janout, V., Jimenez-Murcia, S., Johnson, C., Jordan, J., Julia, A., Jureus, A., Kalsi, G., Kaminska, D., Kaplan, A., Kaprio, J., Karhunen, L., Karwautz, A., Kas, M., Kaye, W., Kennedy, J., Kennedy, M., Keski-Rahkonen, A., Kiezebrink, K., Kim, Y. -R., Kirk, K., Klareskog, L., Klump, K., Knudsen, G. P., La Via, M., Landen, M., Larsen, J., Le Hellard, S., Leppa, V., Levitan, R., Li, D., Lichtenstein, P., Lilenfeld, L., Lin, B. D., Lissowska, J., Luykx, J., Magistretti, P., Maj, M., Mannik, K., Marsal, S., Marshall, C., Martin, N., Mattheisen, M., Mattingsdal, M., Mcdevitt, S., Mcguffin, P., Medland, S., Metspalu, A., Meulenbelt, I., Micali, N., Mitchell, J., Mitchell, K., Monteleone, P., Monteleone, A. M., Montgomery, G., Mortensen, P. B., Munn-Chernoff, M., Nacmias, B., Navratilova, M., Norring, C., Ntalla, I., Olsen, C., Ophoff, R., O'Toole, J., Padyukov, L., Palotie, A., Pantel, J., Papezova, H., Parker, R., Pearson, J., Pedersen, N., Petersen, L., Pinto, D., Purves, K., Rabionet, R., Raevuori, A., Ramoz, N., Reichborn-Kjennerud, T., Ricca, V., Ripatti, S., Ripke, S., Ritschel, F., Roberts, M., Rotondo, A., Rujescu, D., Rybakowski, F., Santonastaso, P., Scherag, A., Scherer, S., Schmidt, U., Schork, N., Schosser, A., Seitz, J., Slachtova, L., Slagboom, P. E., Slof-Op 't Landt, M., Slopien, A., Sorbi, S., Strober, M., Stuber, G., Sullivan, P., Swiatkowska, B., Szatkiewicz, J., Tachmazidou, I., Tenconi, E., Thornton, L., Tortorella, A., Tozzi, F., Treasure, J., Tsitsika, A., Tyszkiewicz-Nwafor, M., Tziouvas, K., van Elburg, A., van Furth, E., Wade, T., Wagner, G., Walton, E., Watson, H., Werge, T., Whiteman, D., Widen, E., Woodside, D. B., Yao, S., Yilmaz, Z., Zeggini, E., Zerwas, S., Zipfel, S., Anttila, V., Artto, V., Belin, A. C., de Boer, I., Boomsma, D. I., Borte, S., Chasman, D. I., Cherkas, L., Christensen, A. F., Cormand, B., Cuenca-Leon, E., Davey-Smith, G., Dichgans, M., van Duijn, C., Esserlind, A. L., Ferrari, M., Frants, R. R., Freilinger, T., Furlotte, N., Gormley, P., Griffiths, L., Hamalainen, E., Hiekkala, M., Ikram, M. A., Ingason, A., Jarvelin, M. -R., Kajanne, R., Kallela, M., Kaunisto, M., Kubisch, C., Kurki, M., Kurth, T., Launer, L., Lehtimaki, T., Lessel, D., Ligthart, L., Litterman, N., Maagdenberg, A., Macaya, A., Malik, R., Mangino, M., Mcmahon, G., Muller-Myhsok, B., Neale, B. M., Northover, C., Nyholt, D. R., Olesen, J., Palta, P., Pedersen, L., Posthuma, D., Pozo-Rosich, P., Pressman, A., Raitakari, O., Schurks, M., Sintas, C., Stefansson, K., Stefansson, H., Steinberg, S., Strachan, D., Terwindt, G., Vila-Pueyo, M., Wessman, M., Winsvold, B. S., Zhao, H., Zwart, J. A., Agee, M., Alipanahi, B., Auton, A., Bell, R., Bryc, K., Elson, S., Fontanillas, P., Heilbron, K., Hinds, D., Huber, K., Kleinman, A., Mccreight, J., Mcintyre, M., Mountain, J., Noblin, E., Pitts, S., Sathirapongsasuti, J., Sazonova, O., Shelton, J., Shringarpure, S., Tian, C., Tung, J., Vacic, V., Wilson, C., Brueggeman, L., Bulik, C. M., Arenas, E., Hjerling-Leffler, J., and Sullivan, P. F.
Subjects: Nervous system, Netherlands Twin Register (NTR), Aging, Parkinson's disease, Medizin, Genome-wide association study, Disease, Neurodegenerative, Medical and Health Sciences, ddc:616.89, Mice, 0302 clinical medicine, Malaltia de Parkinson, Monoaminergic, Eating Disorders Working Group of the Psychiatric Genomics Consortium, 2.1 Biological and endogenous factors, Aetiology, Cervell, ALZHEIMERS, NEURONS, Animals, Brain, Genome-Wide Association Study, Humans, Neurons, Parkinson Disease, Transcriptome, 11 Medical and Health Sciences, Genetics & Heredity, 0303 health sciences, Parkinson Disease/etiology/genetics/pathology, HERITABILITY, International Headache Genetics Consortium, Biological Sciences, Transcriptome/genetics, medicine.anatomical_structure, Neurological, Genome-Wide Association Study/methods, Alzheimer's disease, Life Sciences & Biomedicine, Gens, Cell type, TISSUES, 1.1 Normal biological development and functioning, Biology, IMMUNITY, 23andMe Research Team, Article, 03 medical and health sciences, ENTERIC NERVOUS-SYSTEM, SDG 3 - Good Health and Well-being, Underpinning research, medicine, Genetics, Brain/pathology, GENOME-WIDE ASSOCIATION, NUCLEUS, METAANALYSIS, 030304 developmental biology, Science & Technology, Neurons/pathology, Human Genome, Neurosciences, 06 Biological Sciences, medicine.disease, RISK LOCI, Brain Disorders, Genes, Enteric nervous system, Neuroscience, 030217 neurology & neurosurgery, Developmental Biology
Abstract: Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson’s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson’s disease. Eating Disorders Working Group of the Psychiatric Genomics Consortium Roger Adan17,18,19, Lars Alfredsson20, Tetsuya Ando21, Ole Andreassen22, Jessica Baker9, Andrew Bergen23,24, Wade Berrettini25, Andreas Birgegård26,27, Joseph Boden28, Ilka Boehm29, Claudette Boni30, Vesna Boraska Perica31,32, Harry Brandt33, Gerome Breen13,14, Julien Bryois1, Katharina Buehren34, Cynthia Bulik1,9,15, Roland Burghardt35, Matteo Cassina36, Sven Cichon37, Maurizio Clementi36, Jonathan Coleman13,14, Roger Cone38, Philippe Courtet39, Steven Crawford33, Scott Crow40, James Crowley16,26, unna Danner18, Oliver Davis41,42, Martina de Zwaan43, George Dedoussis44, Daniela Degortes45, Janiece DeSocio46, Danielle Dick47, Dimitris Dikeos48, Christian Dina49,50, Monika Dmitrzak-Weglarz51, Elisa Docampo Martinez52,53,54, Laramie Duncan55, Karin Egberts56, Stefan Ehrlich29, Geòrgia Escaramís52,53,54, Tõnu Esko57,58, Xavier Estivill52,53,54,59, Anne Farmer13, Angela Favaro45, Fernando Fernández-Aranda60,61, Manfred Fichter62,63, Krista Fischer57, Manuel Föcker64, Lenka Foretova65, Andreas Forstner37,66,67,68,69, Monica Forzan36, Christopher Franklin31, Steven Gallinger70, Héléna Gaspar13,14, Ina Giegling71, Johanna Giuranna64, Paola Giusti-Rodríquez16, Fragiskos Gonidakis72, Scott Gordon73, Philip Gorwood30,74, Monica Gratacos Mayora52,53,54, Jakob Grove75,76,77,78, Sébastien Guillaume39, Yiran Guo79, Hakon Hakonarson79,80, Katherine Halmi81, Ken Hanscombe82, Konstantinos Hatzikotoulas31, Joanna Hauser83, Johannes Hebebrand64, Sietske Helder13,84, Anjali Henders85, Stefan Herms37,69, Beate Herpertz-Dahlmann34, Wolfgang Herzog86, Anke Hinney64, L. John Horwood28, Christopher Hübel1,13, Laura Huckins31,87, James Hudson88, Hartmut Imgart89, Hidetoshi Inoko90, Vladimir Janout91, Susana Jiménez-Murcia60,61, Craig Johnson92, Jennifer Jordan93,94, Antonio Julià95, Anders Juréus1, Gursharan Kalsi13, Deborah Kaminská96, Allan Kaplan97, Jaakko Kaprio98,99, Leila Karhunen100, Andreas Karwautz101, Martien Kas17,102, Walter Kaye103, James Kennedy97, Martin Kennedy104, Anna Keski-Rahkonen98, Kirsty Kiezebrink105, Youl-Ri Kim106, Katherine Kirk73, Lars Klareskog107, Kelly Klump108, Gun Peggy Knudsen109, Maria La Via9, Mikael Landén1,19, Janne Larsen76,110,111, Stephanie Le Hellard112,113,114, Virpi Leppä1, Robert Levitan115, Dong Li79, Paul Lichtenstein1, Lisa Lilenfeld116, Bochao Danae Lin17, Jolanta Lissowska117, Jurjen Luykx17, Pierre Magistretti118,119, Mario Maj120, Katrin Mannik57,121, Sara Marsal95, Christian Marshall122, Nicholas Martin73, Manuel Mattheisen26,27,75,123, Morten Mattingsdal22, Sara McDevitt124,125, Peter McGuffin13, Sarah Medland73, Andres Metspalu57,126, Ingrid Meulenbelt127, Nadia Micali128,129, James Mitchell130, Karen Mitchell131, Palmiero Monteleone132, Alessio Maria Monteleone120, Grant Montgomery73,85,133, Preben Bo Mortensen76,110,111, Melissa Munn-Chernoff9, Benedetta Nacmias134, Marie Navratilova65, Claes Norring26,27, Ioanna Ntalla44, Catherine Olsen73, Roel Ophoff17,135, Julie O’Toole136, Leonid Padyukov107, Aarno Palotie58,99,137, Jacques Pantel30, Hana Papezova96, Richard Parker73, John Pearson138, Nancy Pedersen1, Liselotte Petersen76,110,111, Dalila Pinto87, Kirstin Purves13, Raquel Rabionet139,140,141, Anu Raevuori98, Nicolas Ramoz30, Ted Reichborn-Kjennerud109,142, Valdo Ricca134,143, Samuli Ripatti144, Stephan Ripke145,146,147, Franziska Ritschel29,148, Marion Roberts13, Alessandro Rotondo149, Dan Rujescu62,71, Filip Rybakowski150, Paolo Santonastaso151, André Scherag152, Stephen Scherer153, ulrike Schmidt13, Nicholas Schork154, Alexandra Schosser155, Jochen Seitz34, Lenka Slachtova156, P. Eline Slagboom127, Margarita Slof-Op ‘t Landt157,158, Agnieszka Slopien159, Sandro Sorbi134,160, Michael Strober161,162, Garret Stuber9,163, Patrick Sullivan1,16, Beata Świątkowska164, Jin Szatkiewicz16, Ioanna Tachmazidou31, Elena Tenconi45, Laura Thornton9, Alfonso Tortorella165,166, Federica Tozzi167, Janet Treasure13, Artemis Tsitsika168, Marta Tyszkiewicz-Nwafor150, Konstantinos Tziouvas169, Annemarie van Elburg18,170, Eric van Furth157,158, Tracey Wade171, Gudrun Wagner101, Esther Walton29, Hunna Watson9,10,11, Thomas Werge172, David Whiteman73, Elisabeth Widen99, D. Blake Woodside173,174, Shuyang Yao1, Zeynep Yilmaz9,16, Eleftheria Zeggini31,175, Stephanie Zerwas9 and Stephan Zipfel176 17Brain Center Rudolf Magnus, Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands. 18Center for Eating Disorders Rintveld, Altrecht Mental Health Institute, Zeist, the Netherlands. 19Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 20Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. 21Department of Behavioral Medicine, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan. 22NORMENT KG Jebsen Centre, Division of Mental Health and Addiction, University of Oslo, Oslo University Hospital, Oslo, Norway. 23BioRealm, LLC, Walnut, CA, USA. 24Oregon Research Institute, Eugene, OR, USA. 25Department of Psychiatry, Center for Neurobiology and Behavior, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. 26Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. 27Center for Psychiatry Research, Stockholm Health Care Services, Stockholm City Council, Stockholm, Sweden. 28Christchurch Health and Development Study, University of Otago, Christchurch, New Zealand. 29Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany. 30INSERM U894, Centre of Psychiatry and Neuroscience, Paris, France. 31Wellcome Sanger Institute, Hinxton, Cambridge, UK. 32Department of Medical Biology, School of Medicine, University of Split, Split, Croatia. 33The Center for Eating Disorders at Sheppard Pratt, Baltimore, MD, USA. 34Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, RWTH Aachen University, Aachen, Germany. 35Klinikum Frankfurt/Oder, Frankfurt, Germany. 36Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Padua, Italy. 37Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland. 38Life Sciences Institute and Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA. 39Department of Emergency Psychiatry and Post-Acute Care, CHRU Montpellier, University of Montpellier, Montpellier, France. 40Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA. 41MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK. 42School of Social and Community Medicine, University of Bristol, Bristol, UK. 43Department of Psychosomatic Medicine and Psychotherapy, Hannover Medical School, Hannover, Germany. 44Department of Nutrition and Dietetics, Harokopio University, Athens, Greece. 45Department of Neurosciences, University of Padova, Padua, Italy. 46College of Nursing, Seattle University, Seattle, WA, USA. 47Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA. 48Department of Psychiatry, Athens University Medical School, Athens University, Athens, Greece. 49L’institut du thorax, INSERM, CNRS, UNIV Nantes, Nantes, France. 50L’institut du thorax, CHU Nantes, Nantes, France. 51Department of Psychiatric Genetics, Poznań University of Medical Sciences, Poznań, Poland. 52Barcelona Institute of Science and Technology, Barcelona, Spain. 53Universitat Pompeu Fabra, Barcelona, Spain. 54Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. 55Department of Psychiatry and Behavioral Sciences, Stanford University Stanford, CA, USA. 56Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Centre for Mental Health, Würzburg, Germany. 57Estonian Genome Center, University of Tartu, Tartu, Estonia. 58Program in Medical and Population Genetics, Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA. 59Genomics and Disease, Bioinformatics and Genomics Programme, Centre for Genomic Regulation, Barcelona, Spain. 60Department of Psychiatry, University Hospital of Bellvitge –IDIBELL and CIBERobn, Barcelona, Spain. 61Department of Clinical Sciences, School of Medicine, University of Barcelona, Barcelona, Spain. 62Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University (LMU), Munich, Germany. 63Schön Klinik Roseneck affiliated with the Medical Faculty of the University of Munich (LMU), Munich, Germany. 64Department of Child and Adolescent Psychiatry, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. 65Department of Cancer, Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic. 66Institute of Human Genetics, University of Bonn School of Medicine & University Hospital Bonn, Bonn, Germany. 67Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany. 68Department of Psychiatry (UPK), University of Basel, Basel, Switzerland. 69Department of Biomedicine, University of Basel, Basel, Switzerland. 70Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. 71Department of Psychiatry, Psychotherapy and Psychosomatics, Martin Luther University of Halle-Wittenberg, Halle, Germany. 721st Psychiatric Department, National and Kapodistrian University of Athens, Medical School, Eginition Hospital, Athens, Greece. 73QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. 74CMME (Groupe Hospitalier Sainte-Anne), Paris Descartes University, Paris, France. 75Department of Biomedicine, Aarhus University, Aarhus, Denmark. 76The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSyCH), Aarhus, Denmark. 77Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark. 78Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark. 79Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA. 80Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 81Department of Psychiatry, Weill Cornell Medical College, New york, Ny, USA. 82Department of Medical and Molecular Genetics, King’s College London, Guy’s Hospital, London, UK. 83Department of Adult Psychiatry, Poznań University of Medical Sciences, Poznań, Poland. 84Zorg op Orde, Leidschendam, the Netherlands. 85Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. 86Department of General Internal Medicine and Psychosomatics, Heidelberg University Hospital, Heidelberg University, Heidelberg, Germany. 87Department of Psychiatry, and Genetics and Genomics Sciences, Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New york, Ny, USA. 88Biological Psychiatry Laboratory, McLean Hospital/Harvard Medical School, Boston, MA, USA. 89Eating Disorders Unit, Parklandklinik, Bad Wildungen, Germany. 90Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, School of Medicine, Tokai University, Isehara, Japan. 91Faculty of Health Sciences, Palacky University, Olomouc, Czech Republic. 92Eating Recovery Center, Denver, CO, USA. 93Department of Psychological Medicine, University of Otago, Christchurch, New Zealand. 94Canterbury District Health Board, Christchurch, New Zealand. 95Rheumatology Research Group, Vall d’Hebron Research Institute, Barcelona, Spain. 96Department of Psychiatry, First Faculty of Medicine, Charles University, Prague, Czech Republic. 97Center for Addiction and Mental Health, Department of Psychiatry, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. 98Department of Public Health, University of Helsinki, Helsinki, Finland. 99Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland. 100Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland. 101Eating Disorders Unit, Department of Child and Adolescent Psychiatry, Medical University of Vienna, Vienna, Austria. 102Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, the Netherlands. 103Department of Psychiatry, University of California San Diego, San Diego, CA, USA. 104Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand. 105Health Services Research Unit, University of Aberdeen, Aberdeen, UK. 106Department of Psychiatry, Seoul Paik Hospital, Inje University, Seoul, Korea. 107Rheumatology Unit, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. 108Department of Psychology, Michigan State University, East Lansing, MI, USA. 109Department of Mental Disorders, Norwegian Institute of Public Health, Oslo, Norway. 110National Centre for Register-Based Research, Aarhus BSS, Aarhus University, Aarhus, Denmark. 111Centre for Integrated Register-based Research (CIRRAU), Aarhus University, Aarhus, Denmark. 112Department of Clinical Science, K.G. Jebsen Centre for Psychosis Research, Norwegian Centre for Mental Disorders Research (NORMENT), University of Bergen, Bergen, Norway. 113Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway. 114Department of Clinical Medicine, Laboratory Building, Haukeland University Hospital, Bergen, Norway. 115Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. 116American School of Professional Psychology, Argosy University, Northern Virginia, Arlington, VA, USA. 117Department of Cancer Epidemiology and Prevention, M Skłodowska-Curie Cancer Center - Oncology Center, Warsaw, Poland. 118BESE Division, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia. 119Department of Psychiatry, University of Lausanne-University Hospital of Lausanne (UNIL-CHUV), Lausanne, Switzerland. 120Department of Psychiatry, University of Campania ‘Luigi Vanvitelli’, Naples, Italy. 121Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland. 122Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada. 123Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany. 124Department of Psychiatry, University College Cork, Cork, Ireland. 125Eist Linn Adolescent Unit, Bessborough, Health Service Executive South, Cork, Ireland. 126Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia. 127Molecular Epidemiology Section (Department of Medical Statistics), Leiden University Medical Centre, Leiden, the Netherlands. 128Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 129Division of Child and Adolescent Psychiatry, Geneva University Hospital, Geneva, Switzerland. 130Department of Psychiatry and Behavioral Science, University of North Dakota School of Medicine and Health Sciences, Fargo, ND, USA. 131National Center for PTSD, VA Boston Healthcare System, Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA. 132Department of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of Salerno, Salerno, Italy. 133Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia. 134Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy. 135Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA. 136Kartini Clinic, Portland, OR, USA. 137Center for Human Genome Research at the Massachusetts General Hospital, Boston, MA, USA. 138Biostatistics and Computational Biology Unit, University of Otago, Christchurch, New Zealand. 139Saint Joan de Déu Research Institute, Saint Joan de Déu Barcelona Children’s Hospital, Barcelona, Spain. 140Institute of Biomedicine (IBUB), University of Barcelona, Barcelona, Spain. 141Department of Genetics, Microbiology and Statistics, University of Barcelona, Barcelona, Spain. 142Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 143Department of Health Science, University of Florence, Florence, Italy. 144Department of Biometry, University of Helsinki, Helsinki, Finland. 145Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA. 146Stanley Center for Psychiatric Research, Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA. 147Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin, Berlin, Germany. 148Eating Disorders Research and Treatment Center, Department of Child and Adolescent Psychiatry, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany. 149Department of Psychiatry, Neurobiology, Pharmacology, and Biotechnologies, University of Pisa, Pisa, Italy. 150Department of Psychiatry, Poznań University of Medical Sciences, Poznań, Poland. 151Department of Neurosciences, Padua Neuroscience Center, University of Padova, Padua, Italy. 152Institute of Medical Statistics, Computer and Data Sciences, Jena University Hospital, Jena, Germany. 153Department of Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario, Canada. 154J. Craig Venter Institute (JCVI), La Jolla, CA, USA. 155Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria. 156Department of Pediatrics and Center of Applied Genomics, First Faculty of Medicine, Charles University, Prague, Czech Republic. 157Center for Eating Disorders Ursula, Rivierduinen, Leiden, the Netherlands. 158Department of Psychiatry, Leiden University Medical Centre, Leiden, the Netherlands. 159Department of Child and Adolescent Psychiatry, Poznań University of Medical Sciences, Poznań, Poland. 160IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy. 161Department of Psychiatry and Biobehavioral Science, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA. 162David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. 163Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. 164Department of Environmental Epidemiology, Nofer Institute of Occupational Medicine, Lodz, Poland. 165Department of Psychiatry, University of Naples SUN, Naples, Italy. 166Department of Psychiatry, University of Perugia, Perugia, Italy. 167Brain Sciences Department, Stremble Ventures, Limassol, Cyprus. 168Adolescent Health Unit, Second Department of Pediatrics, ‘P. & A. Kyriakou’ Children’s Hospital, University of Athens, Athens, Greece. 169Pediatric Intensive Care Unit, ‘P. & A. Kyriakou’ Children’s Hospital, University of Athens, Athens, Greece. 170Faculty of Social and Behavioral Sciences, Utrecht University, Utrecht, the Netherlands. 171School of Psychology, Flinders University, Adelaide, South Australia, Australia. 172Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. 173Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. 174Toronto General Hospital, Toronto, Ontario, Canada. 175Institute of Translational Genomics, Helmholtz Zentrum München, Neuherberg, Germany. 176Department of Internal Medicine VI, Psychosomatic Medicine and Psychotherapy, University Medical Hospital Tübingen, Tübingen, Germany International Headache Genetics Consortium Verneri Anttila177, Ville Artto178, Andrea Carmine Belin179, Irene de Boer180, Dorret I. Boomsma181, Sigrid Børte182, Daniel I. Chasman183, Lynn Cherkas184, Anne Francke Christensen185, Bru Cormand186, Ester Cuenca-Leon177, George Davey-Smith187, Martin Dichgans188, Cornelia van Duijn189, Tonu Esko57, Ann Louise Esserlind190, Michel Ferrari180, Rune R. Frants180, Tobias Freilinger191, Nick Furlotte192, Padhraig Gormley177, Lyn Griffiths193, Eija Hamalainen194, Thomas Folkmann Hansen6, Marjo Hiekkala195, M. Arfan Ikram189, Andres Ingason196, Marjo-Riitta Järvelin197, Risto Kajanne194, Mikko Kallela178, Jaakko Kaprio98,99, Mari Kaunisto195, Lisette J. A. Kogelman6, Christian Kubisch198, Mitja Kurki177, Tobias Kurth199, Lenore Launer200, Terho Lehtimaki201, Davor Lessel198, Lannie Ligthart181, Nadia Litterman192, Arn van den Maagdenberg180, Alfons Macaya202, Rainer Malik188, Massimo Mangino184, George McMahon187, Bertram Muller-Myhsok203, Benjamin M. Neale177, Carrie Northover192, Dale R. Nyholt193, Jes Olesen190, Aarno Palotie58,99,137, Priit Palta194, Linda Pedersen182, Nancy Pedersen1, Danielle Posthuma181, Patricia Pozo-Rosich204, Alice Pressman205, Olli Raitakari206, Markus Schürks199, Celia Sintas186, Kari Stefansson196, Hreinn Stefansson196, Stacy Steinberg196, David Strachan207, Gisela Terwindt180, Marta Vila-Pueyo202, Maija Wessman195, Bendik S. Winsvold182, Huiying Zhao193 and John Anker Zwart182 177Broad Institute of MIT and Harvard, Cambridge, MA, USA. 178Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland. 179Karolinska Institutet, Stockholm, Sweden. 180Leiden University Medical Centre, Leiden, the Netherlands. 181VU University, Amsterdam, the Netherlands. 182Oslo University Hospital and University of Oslo, Oslo, Norway. 183Harvard Medical School, Cambridge, MA, USA. 184Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK. 185Danish Headache Center, Copenhagen University Hospital, Copenhagen, Denmark. 186University of Barcelona, Barcelona, Spain. 187Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK. 188Institute for Stroke and Dementia Research, Munich, Germany. 189Erasmus University Medical Centre, Rotterdam, the Netherlands. 190Danish Headache Center, Department of Neurology, Rigshospitalet, Glostrup, Denmark. 191University of Tübingen, Tübingen, Germany. 19223&Me Inc., Mountain View, CA, USA. 193Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia. 194Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. 195Folkhälsan Institute of Genetics, Helsinki, Finland. 196Decode genetics Inc., Reykjavik, Iceland. 197University of Oulu, Biocenter Oulu, Finland. 198University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 199Harvard Medical School, Boston, MA, USA. 200National Institute on Aging, Bethesda, MD, USA. 201School of Medicine, University of Tampere, Tampere, Finland. 202Vall d’Hebron Research Institute, Barcelona, Spain. 203Max Planck Institute of Psychiatry, Munich, Germany. 204Headache Research Group, Universitat Autònoma de Barcelona, Barcelona, Spain. 205Sutter Health, Sacramento, CA, USA. 206Department of Medicine, University of Turku, Turku, Finland. 207Population Health Research Institute, St George’s University of London, London, UK. 23andMe Research Team Michelle Agee208, Babak Alipanahi208, Adam Auton208, Robert Bell208, Katarzyna Bryc208, Sarah Elson208, Pierre Fontanillas208, Nicholas Furlotte208, Karl Heilbron208, David Hinds208, Karen Huber208, Aaron Kleinman208, Nadia Litterman208, Jennifer McCreight208, Matthew McIntyre208, Joanna Mountain208, Elizabeth Noblin208, Carrie Northover208, Steven Pitts208, J. Sathirapongsasuti208, Olga Sazonova208, Janie Shelton208, Suyash Shringarpure208, Chao Tian208, Joyce Tung208, Vladimir Vacic208 and Catherine Wilson208 20823andMe, Inc., Mountain View, CA, US
Published: 2020

2. GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

Author: Franceschini, N, Giambartolomei, C, de Vries, PS, Finan, C, Bis, JC, Huntley, RP, Lovering, RC, Tajuddin, SM, Winkler, TW, Graff, M, Kavousi, M, Dale, C, Smith, AV, Hofer, E, van Leeuwen, EM, Nolte, IM, Lu, L, Scholz, M, Sargurupremraj, M, Pitkanen, N, Franzen, O, Joshi, PK, Noordam, R, Marioni, RE, Hwang, S-J, Musani, SK, Schminke, U, Palmas, W, Isaacs, A, Correa, A, Zonderman, AB, Hofman, A, Teumer, A, Cox, AJ, Uitterlinden, AG, Wong, A, Smit, AJ, Newman, AB, Britton, A, Ruusalepp, A, Sennblad, B, Hedblad, B, Pasaniuc, B, Penninx, BW, Langefeld, CD, Wassel, CL, Tzourio, C, Fava, C, Baldassarre, D, O'Leary, DH, Teupser, D, Kuh, D, Tremoli, E, Mannarino, E, Grossi, E, Boerwinkle, E, Schadt, EE, Ingelsson, E, Veglia, F, Rivadeneira, F, Beutner, F, Chauhan, G, Heiss, G, Snieder, H, Campbell, H, Voelzke, H, Markus, HS, Deary, IJ, Jukema, JW, de Graaf, J, Price, J, Pott, J, Hopewell, JC, Liang, J, Thiery, J, Engmann, J, Gertow, K, Rice, K, Taylor, KD, Dhana, K, Kiemeney, LALM, Lind, L, Raffield, LM, Launer, LJ, Holdt, LM, Doer, M, Dichgans, M, Traylor, M, Sitzer, M, Kumari, M, Kivimaki, M, Nalls, MA, Melander, O, Raitakari, O, Franco, OH, Rueda-Ochoa, OL, Roussos, P, Whincup, PH, Amouyel, P, Giral, P, Anugu, P, Wong, Q, Malik, R, Rauramaa, R, Burkhardt, R, Hardy, R, Schmidt, R, de Mutsert, R, Morris, RW, Strawbridge, RJ, Wannamethee, SG, Hagg, S, Shah, S, McLachlan, S, Trompet, S, Seshadri, S, Kurl, S, Heckbert, SR, Ring, S, Harris, TB, Lehtimaki, T, Galesloot, TE, Shah, T, de Faire, U, Plagnol, V, Rosamond, WD, Post, W, Zhu, X, Zhang, X, Guo, X, Saba, Y, Dehghan, A, Seldenrijk, A, Morrison, AC, Hamsten, A, Psaty, BM, van Duijn, CM, Lawlor, DA, Mook-Kanamori, DO, Bowden, DW, Schmidt, H, Wilson, JF, Wilson, JG, Rotter, JI, Wardlaw, JM, Deanfield, J, Halcox, J, Lyytikainen, L-P, Loeffler, M, Evans, MK, Debette, S, Humphries, SE, Voelker, U, Gudnason, V, Hingorani, AD, Bjorkegren, JLM, Casas, JP, O'Donnell, CJ, Franceschini, N, Giambartolomei, C, de Vries, PS, Finan, C, Bis, JC, Huntley, RP, Lovering, RC, Tajuddin, SM, Winkler, TW, Graff, M, Kavousi, M, Dale, C, Smith, AV, Hofer, E, van Leeuwen, EM, Nolte, IM, Lu, L, Scholz, M, Sargurupremraj, M, Pitkanen, N, Franzen, O, Joshi, PK, Noordam, R, Marioni, RE, Hwang, S-J, Musani, SK, Schminke, U, Palmas, W, Isaacs, A, Correa, A, Zonderman, AB, Hofman, A, Teumer, A, Cox, AJ, Uitterlinden, AG, Wong, A, Smit, AJ, Newman, AB, Britton, A, Ruusalepp, A, Sennblad, B, Hedblad, B, Pasaniuc, B, Penninx, BW, Langefeld, CD, Wassel, CL, Tzourio, C, Fava, C, Baldassarre, D, O'Leary, DH, Teupser, D, Kuh, D, Tremoli, E, Mannarino, E, Grossi, E, Boerwinkle, E, Schadt, EE, Ingelsson, E, Veglia, F, Rivadeneira, F, Beutner, F, Chauhan, G, Heiss, G, Snieder, H, Campbell, H, Voelzke, H, Markus, HS, Deary, IJ, Jukema, JW, de Graaf, J, Price, J, Pott, J, Hopewell, JC, Liang, J, Thiery, J, Engmann, J, Gertow, K, Rice, K, Taylor, KD, Dhana, K, Kiemeney, LALM, Lind, L, Raffield, LM, Launer, LJ, Holdt, LM, Doer, M, Dichgans, M, Traylor, M, Sitzer, M, Kumari, M, Kivimaki, M, Nalls, MA, Melander, O, Raitakari, O, Franco, OH, Rueda-Ochoa, OL, Roussos, P, Whincup, PH, Amouyel, P, Giral, P, Anugu, P, Wong, Q, Malik, R, Rauramaa, R, Burkhardt, R, Hardy, R, Schmidt, R, de Mutsert, R, Morris, RW, Strawbridge, RJ, Wannamethee, SG, Hagg, S, Shah, S, McLachlan, S, Trompet, S, Seshadri, S, Kurl, S, Heckbert, SR, Ring, S, Harris, TB, Lehtimaki, T, Galesloot, TE, Shah, T, de Faire, U, Plagnol, V, Rosamond, WD, Post, W, Zhu, X, Zhang, X, Guo, X, Saba, Y, Dehghan, A, Seldenrijk, A, Morrison, AC, Hamsten, A, Psaty, BM, van Duijn, CM, Lawlor, DA, Mook-Kanamori, DO, Bowden, DW, Schmidt, H, Wilson, JF, Wilson, JG, Rotter, JI, Wardlaw, JM, Deanfield, J, Halcox, J, Lyytikainen, L-P, Loeffler, M, Evans, MK, Debette, S, Humphries, SE, Voelker, U, Gudnason, V, Hingorani, AD, Bjorkegren, JLM, Casas, JP, and O'Donnell, CJ
Abstract: Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
Published: 2018

3. Carotid artery compliance in users of plant stanol ester margarine

Author: Raitakari, O T, Salo, P, and Ahotupa, M
Subjects: Margarine -- Health aspects, Blood circulation disorders -- Risk factors, Blood circulation disorders -- Prevention
Abstract: Objective: To investigate the effects of stanol ester margarine use in healthy subjects on arterial compliance, endothelial function and intima-media thickness. Design: Case-control study comparing regular stanol ester margarine users to non-users. Setting: Occupational health service clinic. Subjects: We recruited 50 cases and 50 controls (mean age 51[plus or minus]8, range 26-65 years). All subjects were non-smokers and the study groups were matched for age and sex. As cases, we invited subjects who had been using regularly (daily) plant stanol ester margarine for a period of 2 years or longer. Non-invasive ultrasound was used to measure carotid artery compliance, carotid intima-media thickness and brachial artery flow-mediated endothelial dependent vasodilatation. Results: The carotid artery compliance was non-significantly higher in cases compared with controls, 1.84[plus or minus]1.02 vs 1.58[plus or minus]0.76 %/10 mm Hg (P=0.13). The difference in compliance became statistically significant (P=0.04) when the unbalance between the groups in family history of coronary artery disease and years of education were taken into account. There was also a significant dose-response relationship between stanol margarine use and carotid compliance, longer use being associated with higher compliance. Serum lipoproteins, blood pressure, flow-mediated dilation and intima-media thickness values did not differ between cases and controls. Conclusion: These data raise the possibility that regular stanol ester margarine use may be associated with beneficial changes in arterial compliance. Intervention studies are needed to test this hypothesis and to reveal possible mechanisms. European Journal of Clinical Nutrition (2008) 62, 218-224; doi: 10.1038/sj.ejcn.1602705; published online 14 March 2007 Keywords: stanol ester, ultrasound, vascular, endothelial, Author(s): O T Raitakari [1]; P Salo [2]; M Ahotupa [3] Introduction Plant stanols inhibit the absorption of both exogenous dietary and endogenous biliary cholesterol from the proximal small intestine. [...]
Published: 2008
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4. Longitudinal changes in diet from childhood into adulthood with respect to risk of cardiovascular diseases: The Cardiovascular Risk in Young Finns Study

Author: Mikkila, V, Rasanen, L, Raitakari, O T, Pietinen, P, and Viikari, J
Abstract: Objective:: To assess nutrient intakes relevant in the prevention of cardiovascular diseases (CVD) among young adults in Finland and to find past and present determinants of quality of diet. Design:: Prospective study, 21 years of follow-up. Setting:: The Cardiovascular Risk in Young Finns Study, Finland. Subjects:: At baseline in 1980: 3569 children aged 3-18 y participated (83% of those invited), and every second of them (1780) were selected to the dietary study. At follow-ups in 1986 and 2001: 1200 and 1037 of the original sample, respectively, participated. Methods:: Food consumption was assessed using 48-h dietary recall. Intakes in 2001 were compared with those obtained in 1980 and 1986. Nutrients selected for further examination were those implicated in the risk of CVD: saturated, monounsaturated, polyunsaturated and n-3 fatty acids, fibre and salt. An index describing the quality of adulthood diet was constructed. Multivariate logistic regression was used to identify independent childhood and adulthood determinants of the quality index. Results:: The average intakes showed substantial changes since 1980. Intakes of fat and saturated fat had decreased, while the consumption of vegetables and fruit had increased. However, a great disparity was present between the recommended levels and actual intakes for many of the nutrients, particularly salt, saturated fat and fibre. Intake of fat and consumption of vegetables in childhood and physical activity in adulthood were important health behavioural determinants of the cardiovascular quality of the adult diet. Socio-demographic factors, including education of the subject and their parents, had no significant associations with diet. Conclusions:: While intakes of energy and nutrients have changed favourably in Finnish young adults between 1980 and 2001 with regard to the risk of CVD, they are still far from recommended levels. Childhood diet is a significant determinant of adult diet even after 21 y. Sponsorship:: This study was supported by the Academy of Finland (grant 77841) and Juho Vainio Foundation. European Journal of Clinical Nutrition (2004) 58, 1038-1045. doi: 10.1038/sj.ejcn.1601929 Keywords: cardiovascular diseases, longitudinal studies, diet, Finland, health behaviour, Author(s): V Mikkila [1]; L Rasanen [1]; O T Raitakari [2]; P Pietinen [3]; J Viikari [4] Introduction The association between diet and cardiovascular diseases (CVD) has been indisputably shown [...]
Published: 2004
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5. Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error

Author: Fan, Q, Verhoeven, VJM, Wojciechowski, R, Barathi, VA, Hysi, PG, Guggenheim, JA, Hoehn, R, Vitart, V, Khawaja, AP, Yamashiro, K, Hosseini, SM, Lehtimaki, T, Lu, Y, Haller, T, Xie, J, Delcourt, C, Pirastu, M, Wedenoja, J, Gharahkhani, P, Venturini, C, Miyake, M, Hewitt, AW, Guo, X, Mazur, J, Huffman, JE, Williams, KM, Polasek, O, Campbell, H, Rudan, I, Vatavuk, Z, Wilson, JF, Joshi, PK, McMahon, G, St Pourcain, B, Evans, DM, Simpson, CL, Schwantes-An, T-H, Igo, RP, Mirshahi, A, Cougnard-Gregoire, A, Bellenguez, C, Blettner, M, Raitakari, O, Kaehoenen, M, Seppala, I, Zeller, T, Meitinger, T, Ried, JS, Gieger, C, Portas, L, van Leeuwen, EM, Amin, N, Uitterlinden, AG, Rivadeneira, F, Hofman, A, Vingerling, JR, Wang, YX, Wang, X, Boh, ET-H, Ikram, MK, Sabanayagam, C, Gupta, P, Tan, V, Zhou, L, Ho, CEH, Lim, W, Beuerman, RW, Siantar, R, Tai, E-S, Vithana, E, Mihailov, E, Khor, C-C, Hayward, C, Luben, RN, Foster, PJ, Klein, BEK, Klein, R, Wong, H-S, Mitchell, P, Metspalu, A, Aung, T, Young, TL, He, M, Paerssinen, O, van Duijn, CM, Wang, JJ, Williams, C, Jonas, JB, Teo, Y-Y, David, AMM, Oexle, K, Yoshimura, N, Paterson, AD, Pfeiffer, N, Wong, T-Y, Baird, PN, Stambolian, D, Bailey-Wilson, JE, Cheng, C-Y, Hammond, CJ, Klaver, CCW, Saw, S-M, Rahi, JS, Korobelnik, J-F, Kemp, JP, Timpson, NJ, Smith, GD, Craig, JE, Burdon, KP, Fogarty, RD, Iyengar, SK, Chew, E, Janmahasatian, S, Martin, NG, MacGregor, S, Xu, L, Schache, M, Nangia, V, Panda-Jonas, S, Wright, AF, Fondran, JR, Lass, JH, Feng, S, Zhao, JH, Khaw, K-T, Wareham, NJ, Rantanen, T, Kaprio, J, Pang, CP, Chen, LJ, Tam, PO, Jhanji, V, Young, AL, Doering, A, Raffel, LJ, Cotch, M-F, Li, X, Yip, SP, Yap, MKH, Biino, G, Vaccargiu, S, Fossarello, M, Fleck, B, Yazar, S, Tideman, JWL, Tedja, M, Deangelis, MM, Morrison, M, Farrer, L, Zhou, X, Chen, W, Mizuki, N, Meguro, A, Makela, KM, Fan, Q, Verhoeven, VJM, Wojciechowski, R, Barathi, VA, Hysi, PG, Guggenheim, JA, Hoehn, R, Vitart, V, Khawaja, AP, Yamashiro, K, Hosseini, SM, Lehtimaki, T, Lu, Y, Haller, T, Xie, J, Delcourt, C, Pirastu, M, Wedenoja, J, Gharahkhani, P, Venturini, C, Miyake, M, Hewitt, AW, Guo, X, Mazur, J, Huffman, JE, Williams, KM, Polasek, O, Campbell, H, Rudan, I, Vatavuk, Z, Wilson, JF, Joshi, PK, McMahon, G, St Pourcain, B, Evans, DM, Simpson, CL, Schwantes-An, T-H, Igo, RP, Mirshahi, A, Cougnard-Gregoire, A, Bellenguez, C, Blettner, M, Raitakari, O, Kaehoenen, M, Seppala, I, Zeller, T, Meitinger, T, Ried, JS, Gieger, C, Portas, L, van Leeuwen, EM, Amin, N, Uitterlinden, AG, Rivadeneira, F, Hofman, A, Vingerling, JR, Wang, YX, Wang, X, Boh, ET-H, Ikram, MK, Sabanayagam, C, Gupta, P, Tan, V, Zhou, L, Ho, CEH, Lim, W, Beuerman, RW, Siantar, R, Tai, E-S, Vithana, E, Mihailov, E, Khor, C-C, Hayward, C, Luben, RN, Foster, PJ, Klein, BEK, Klein, R, Wong, H-S, Mitchell, P, Metspalu, A, Aung, T, Young, TL, He, M, Paerssinen, O, van Duijn, CM, Wang, JJ, Williams, C, Jonas, JB, Teo, Y-Y, David, AMM, Oexle, K, Yoshimura, N, Paterson, AD, Pfeiffer, N, Wong, T-Y, Baird, PN, Stambolian, D, Bailey-Wilson, JE, Cheng, C-Y, Hammond, CJ, Klaver, CCW, Saw, S-M, Rahi, JS, Korobelnik, J-F, Kemp, JP, Timpson, NJ, Smith, GD, Craig, JE, Burdon, KP, Fogarty, RD, Iyengar, SK, Chew, E, Janmahasatian, S, Martin, NG, MacGregor, S, Xu, L, Schache, M, Nangia, V, Panda-Jonas, S, Wright, AF, Fondran, JR, Lass, JH, Feng, S, Zhao, JH, Khaw, K-T, Wareham, NJ, Rantanen, T, Kaprio, J, Pang, CP, Chen, LJ, Tam, PO, Jhanji, V, Young, AL, Doering, A, Raffel, LJ, Cotch, M-F, Li, X, Yip, SP, Yap, MKH, Biino, G, Vaccargiu, S, Fossarello, M, Fleck, B, Yazar, S, Tideman, JWL, Tedja, M, Deangelis, MM, Morrison, M, Farrer, L, Zhou, X, Chen, W, Mizuki, N, Meguro, A, and Makela, KM
Abstract: Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10(-5)), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia.
Published: 2016

6. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

Author: Pattaro, C, Teumer, A, Gorski, M, Chu, AY, Li, M, Mijatovic, V, Garnaas, M, Tin, A, Sorice, R, Li, Y, Taliun, D, Olden, M, Foster, M, Yang, Q, Chen, M-H, Pers, TH, Johnson, AD, Ko, Y-A, Fuchsberger, C, Tayo, B, Nalls, M, Feitosa, MF, Isaacs, A, Dehghan, A, d'Adamo, P, Adeyemo, A, Dieffenbach, AK, Zonderman, AB, Nolte, IM, van der Most, PJ, Wright, AF, Shuldiner, AR, Morrison, AC, Hofman, A, Smith, AV, Dreisbach, AW, Franke, A, Uitterlinden, AG, Metspalu, A, Tonjes, A, Lupo, A, Robino, A, Johansson, A, Demirkan, A, Kollerits, B, Freedman, BI, Ponte, B, Oostra, BA, Paulweber, B, Kraemer, BK, Mitchell, BD, Buckley, BM, Peralta, CA, Hayward, C, Helmer, C, Rotimi, CN, Shaffer, CM, Mueller, C, Sala, C, van Duijn, CM, Saint-Pierre, A, Ackermann, D, Shriner, D, Ruggiero, D, Toniolo, D, Lu, Y, Cusi, D, Czamara, D, Ellinghaus, D, Siscovick, DS, Ruderfer, D, Gieger, C, Grallert, H, Rochtchina, E, Atkinson, EJ, Holliday, EG, Boerwinkle, E, Salvi, E, Bottinger, EP, Murgia, F, Rivadeneira, F, Ernst, F, Kronenberg, F, Hu, FB, Navis, GJ, Curhan, GC, Ehret, GB, Homuth, G, Coassin, S, Thun, G-A, Pistis, G, Gambaro, G, Malerba, G, Montgomery, GW, Eiriksdottir, G, Jacobs, G, Li, G, Wichmann, H-E, Campbell, H, Schmidt, H, Wallaschofski, H, Voelzke, H, Brenner, H, Kroemer, HK, Kramer, H, Lin, H, Leach, IM, Ford, I, Guessous, I, Rudan, I, Prokopenko, I, Borecki, I, Heid, IM, Kolcic, I, Persico, I, Jukema, JW, Wilson, JF, Felix, JF, Divers, J, Lambert, J-C, Stafford, JM, Gaspoz, J-M, Smith, JA, Faul, JD, Wang, JJ, Ding, J, Hirschhorn, JN, Attia, J, Whitfield, JB, Chalmers, J, Viikari, J, Coresh, J, Denny, JC, Karjalainen, J, Fernandes, JK, Endlich, K, Butterbach, K, Keene, KL, Lohman, K, Portas, L, Launer, LJ, Lyytikaeinen, L-P, Yengo, L, Franke, L, Ferrucci, L, Rose, LM, Kedenko, L, Rao, M, Struchalin, M, Kleber, ME, Cavalieri, M, Haun, M, Cornelis, MC, Ciullo, M, Pirastu, M, de Andrade, M, McEvoy, MA, Woodward, M, Adam, M, Cocca, M, Nauck, M, Imboden, M, Waldenberger, M, Pruijm, M, Metzger, M, Stumvoll, M, Evans, MK, Sale, MM, Kaehoenen, M, Boban, M, Bochud, M, Rheinberger, M, Verweij, N, Bouatia-Naji, N, Martin, NG, Hastie, N, Probst-Hensch, N, Soranzo, N, Devuyst, O, Raitakari, O, Gottesman, O, Franco, OH, Polasek, O, Gasparini, P, Munroe, PB, Ridker, PM, Mitchell, P, Muntner, P, Meisinger, C, Smit, JH, Kovacs, P, Wild, PS, Froguel, P, Rettig, R, Maegi, R, Biffar, R, Schmidt, R, Middelberg, RPS, Carroll, RJ, Penninx, BW, Scott, RJ, Katz, R, Sedaghat, S, Wild, SH, Kardia, SLR, Ulivi, S, Hwang, S-J, Enroth, S, Kloiber, S, Trompet, S, Stengel, B, Hancock, SJ, Turner, ST, Rosas, SE, Stracke, S, Harris, TB, Zeller, T, Zemunik, T, Lehtimaeki, T, Illig, T, Aspelund, T, Nikopensius, T, Esko, T, Tanaka, T, Gyllensten, U, Voelker, U, Emilsson, V, Vitart, V, Aalto, V, Gudnason, V, Chouraki, V, Chen, W-M, Igl, W, Maerz, W, Koenig, W, Lieb, W, Loos, RJF, Liu, Y, Snieder, H, Pramstaller, PP, Parsa, A, O'Connell, JR, Susztak, K, Hamet, P, Tremblay, J, de Boer, IH, Boeger, CA, Goessling, W, Chasman, DI, Koettgen, A, Kao, WHL, Fox, CS, Pattaro, C, Teumer, A, Gorski, M, Chu, AY, Li, M, Mijatovic, V, Garnaas, M, Tin, A, Sorice, R, Li, Y, Taliun, D, Olden, M, Foster, M, Yang, Q, Chen, M-H, Pers, TH, Johnson, AD, Ko, Y-A, Fuchsberger, C, Tayo, B, Nalls, M, Feitosa, MF, Isaacs, A, Dehghan, A, d'Adamo, P, Adeyemo, A, Dieffenbach, AK, Zonderman, AB, Nolte, IM, van der Most, PJ, Wright, AF, Shuldiner, AR, Morrison, AC, Hofman, A, Smith, AV, Dreisbach, AW, Franke, A, Uitterlinden, AG, Metspalu, A, Tonjes, A, Lupo, A, Robino, A, Johansson, A, Demirkan, A, Kollerits, B, Freedman, BI, Ponte, B, Oostra, BA, Paulweber, B, Kraemer, BK, Mitchell, BD, Buckley, BM, Peralta, CA, Hayward, C, Helmer, C, Rotimi, CN, Shaffer, CM, Mueller, C, Sala, C, van Duijn, CM, Saint-Pierre, A, Ackermann, D, Shriner, D, Ruggiero, D, Toniolo, D, Lu, Y, Cusi, D, Czamara, D, Ellinghaus, D, Siscovick, DS, Ruderfer, D, Gieger, C, Grallert, H, Rochtchina, E, Atkinson, EJ, Holliday, EG, Boerwinkle, E, Salvi, E, Bottinger, EP, Murgia, F, Rivadeneira, F, Ernst, F, Kronenberg, F, Hu, FB, Navis, GJ, Curhan, GC, Ehret, GB, Homuth, G, Coassin, S, Thun, G-A, Pistis, G, Gambaro, G, Malerba, G, Montgomery, GW, Eiriksdottir, G, Jacobs, G, Li, G, Wichmann, H-E, Campbell, H, Schmidt, H, Wallaschofski, H, Voelzke, H, Brenner, H, Kroemer, HK, Kramer, H, Lin, H, Leach, IM, Ford, I, Guessous, I, Rudan, I, Prokopenko, I, Borecki, I, Heid, IM, Kolcic, I, Persico, I, Jukema, JW, Wilson, JF, Felix, JF, Divers, J, Lambert, J-C, Stafford, JM, Gaspoz, J-M, Smith, JA, Faul, JD, Wang, JJ, Ding, J, Hirschhorn, JN, Attia, J, Whitfield, JB, Chalmers, J, Viikari, J, Coresh, J, Denny, JC, Karjalainen, J, Fernandes, JK, Endlich, K, Butterbach, K, Keene, KL, Lohman, K, Portas, L, Launer, LJ, Lyytikaeinen, L-P, Yengo, L, Franke, L, Ferrucci, L, Rose, LM, Kedenko, L, Rao, M, Struchalin, M, Kleber, ME, Cavalieri, M, Haun, M, Cornelis, MC, Ciullo, M, Pirastu, M, de Andrade, M, McEvoy, MA, Woodward, M, Adam, M, Cocca, M, Nauck, M, Imboden, M, Waldenberger, M, Pruijm, M, Metzger, M, Stumvoll, M, Evans, MK, Sale, MM, Kaehoenen, M, Boban, M, Bochud, M, Rheinberger, M, Verweij, N, Bouatia-Naji, N, Martin, NG, Hastie, N, Probst-Hensch, N, Soranzo, N, Devuyst, O, Raitakari, O, Gottesman, O, Franco, OH, Polasek, O, Gasparini, P, Munroe, PB, Ridker, PM, Mitchell, P, Muntner, P, Meisinger, C, Smit, JH, Kovacs, P, Wild, PS, Froguel, P, Rettig, R, Maegi, R, Biffar, R, Schmidt, R, Middelberg, RPS, Carroll, RJ, Penninx, BW, Scott, RJ, Katz, R, Sedaghat, S, Wild, SH, Kardia, SLR, Ulivi, S, Hwang, S-J, Enroth, S, Kloiber, S, Trompet, S, Stengel, B, Hancock, SJ, Turner, ST, Rosas, SE, Stracke, S, Harris, TB, Zeller, T, Zemunik, T, Lehtimaeki, T, Illig, T, Aspelund, T, Nikopensius, T, Esko, T, Tanaka, T, Gyllensten, U, Voelker, U, Emilsson, V, Vitart, V, Aalto, V, Gudnason, V, Chouraki, V, Chen, W-M, Igl, W, Maerz, W, Koenig, W, Lieb, W, Loos, RJF, Liu, Y, Snieder, H, Pramstaller, PP, Parsa, A, O'Connell, JR, Susztak, K, Hamet, P, Tremblay, J, de Boer, IH, Boeger, CA, Goessling, W, Chasman, DI, Koettgen, A, Kao, WHL, and Fox, CS
Abstract: Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
Published: 2016

7. Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Author: Bis, JC, Kavousi, M, Franceschini, N, Isaacs, A, Abecasis, GR, Schminke, U, Post, WS, Smith, AV, Cupples, LA, Markus, HS, Schmidt, R, Huffman, JE, Lehtimäki, T, Baumert, J, Münzel, T, Heckbert, SR, Dehghan, A, North, K, Oostra, B, Bevan, S, Stoegerer, EM, Hayward, C, Raitakari, O, Meisinger, C, Schillert, A, Sanna, S, Völzke, H, Cheng, YC, Thorsson, B, Fox, CS, Rice, K, Rivadeneira, F, Nambi, V, Halperin, E, Petrovic, KE, Peltonen, L, Wichmann, HE, Schnabel, RB, Dörr, M, Parsa, A, Aspelund, T, Demissie, S, Kathiresan, S, Reilly, MP, Taylor, K, Uitterlinden, A, Couper, DJ, Sitzer, M, Kähönen, M, Illig, T, Wild, PS, Orru, M, Lüdemann, J, Shuldiner, AR, Eiriksdottir, G, White, CC, Rotter, JI, Hofman, A, Seissler, J, Zeller, T, Usala, G, Ernst, F, Launer, LJ, D'Agostino, RB, O'Leary, DH, Ballantyne, C, Thiery, J, Ziegler, A, Lakatta, EG, Chilukoti, RK, Harris, TB, Wolf, PA, Psaty, BM, Polak, JF, Li, X, Rathmann, W, Uda, M, Boerwinkle, E, Klopp, N, Schmidt, H, Wilson, JF, Viikari, J, Koenig, W, Blankenberg, S, Newman, AB, Witteman, J, Heiss, G, Duijn, CV, Scuteri, A, Homuth, G, Mitchell, BD, Gudnason, V, O'Donnell, CJ, and CARDIoGRAM Consortium
Subjects: cardiovascular system, cardiovascular diseases
Published: 2011

8. Defining the role of common variation in the genomic and biological architecture of adult human height

Author: Wood, A, Esko, T, Yang, J, Vedantam, S, Pers, T, Gustafsson, S, Chu, A, Estrada, K, Luan, J, Kutalik, Z, Amin, N, Buchkovich, M, Croteau Chonka, D, Day, F, Duan, Y, Fall, T, Fehrmann, R, Ferreira, T, Jackson, A, Karjalainen, J, Lo, K, Locke, A, Mägi, R, Mihailov, E, Porcu, E, Randall, J, Scherag, A, Vinkhuyzen, A, Westra, H, Winkler, T, Workalemahu, T, Zhao, J, Absher, D, Albrecht, E, Anderson, D, Baron, J, Beekman, M, Demirkan, A, Ehret, G, Feenstra, B, Feitosa, M, Fischer, K, Fraser, R, Goel, A, Gong, J, Justice, A, Kanoni, S, Kleber, M, Kristiansson, K, Lim, U, Lotay, V, Lui, J, Mangino, M, Leach, I, Medina Gomez, C, Nalls, M, Nyholt, D, Palmer, C, Pasko, D, Pechlivanis, S, Prokopenko, I, Ried, J, Ripke, S, Shungin, D, Stancáková, A, Strawbridge, R, Sung, Y, Tanaka, T, Teumer, A, Trompet, S, Van Der Laan, S, Van Setten, J, Van Vliet Ostaptchouk, J, Wang, Z, Yengo, L, Zhang, W, Afzal, U, Ärnlöv, J, Arscott, G, Bandinelli, S, Barrett, A, Bellis, C, Bennett, A, Berne, C, Blüher, M, Bolton, J, Böttcher, Y, Boyd, H, Bruinenberg, M, Buckley, B, Buyske, S, Caspersen, I, Chines, P, Clarke, R, Claudi Boehm, S, Cooper, M, Daw, E, De Jong, P, Deelen, J, Delgado, G, Denny, J, Dhonukshe Rutten, R, Dimitriou, M, Doney, A, Dörr, M, Eklund, N, Eury, E, Folkersen, L, Garcia, M, Geller, F, Giedraitis, V, Go, A, Grallert, H, Grammer, T, Gräßler, J, Grönberg, H, De Groot, L, Groves, C, Haessler, J, Hall, P, Haller, T, Hallmans, G, Hannemann, A, Hartman, C, Hassinen, M, Hayward, C, Heard Costa, N, Helmer, Q, Hemani, G, Henders, A, Hillege, H, Hlatky, M, Hoffmann, W, Hoffmann, P, Holmen, O, Houwing Duistermaat, J, Illig, T, Isaacs, A, James, A, Jeff, J, Johansen, B, Johansson, Å, Jolley, J, Juliusdottir, T, Junttila, J, Kho, A, Kinnunen, L, Klopp, N, Kocher, T, Kratzer, W, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Lu, Y, Lyssenko, V, Magnusson, P, Mahajan, A, Maillard, M, Mcardle, W, Mckenzie, C, Mclachlan, S, Mclaren, P, Menni, C, Merger, S, Milani, L, Moayyeri, A, Monda, K, Morken, M, Müller, G, Müller Nurasyid, M, Musk, A, Narisu, N, Nauck, M, Nolte, I, Nöthen, M, Oozageer, L, Pilz, S, Rayner, N, Renstrom, F, Robertson, N, Rose, L, Roussel, R, Sanna, S, Scharnagl, H, Scholtens, S, Schumacher, F, Schunkert, H, Scott, R, Sehmi, J, Seufferlein, T, Shi, J, Silventoinen, K, Smit, J, Smith, A, Smolonska, J, Stanton, A, Stirrups, K, Stott, D, Stringham, H, Sundström, J, Swertz, M, Syvänen, A, Tayo, B, Thorleifsson, G, Tyrer, J, Van Dijk, S, Van Schoor, N, Van Der Velde, N, Van Heemst, D, Van Oort, F, Vermeulen, S, Verweij, N, Vonk, J, Waite, L, Waldenberger, M, Wennauer, R, Wilkens, L, Willenborg, C, Wilsgaard, T, Wojczynski, M, Wong, A, Wright, A, Zhang, Q, Arveiler, D, Bakker, S, Beilby, J, Bergman, R, Bergmann, S, Biffar, R, Blangero, J, Boomsma, D, Bornstein, S, Bovet, P, Brambilla, P, Brown, M, Campbell, H, Caulfield, M, Chakravarti, A, Collins, R, Collins, F, Crawford, D, Cupples, L, Danesh, J, De Faire, U, Den Ruijter, H, Erbel, R, Erdmann, J, Eriksson, J, Farrall, M, Ferrannini, E, Ferrières, J, Ford, I, Forouhi, N, Forrester, T, Gansevoort, R, Gejman, P, Gieger, C, Golay, A, Gottesman, O, Gudnason, V, Gyllensten, U, Haas, D, Hall, A, Harris, T, Hattersley, A, Heath, A, Hengstenberg, C, Hicks, A, Hindorff, L, Hingorani, A, Hofman, A, Hovingh, G, Humphries, S, Hunt, S, Hypponen, E, Jacobs, K, Jarvelin, M, Jousilahti, P, Jula, A, Kaprio, J, Kastelein, J, Kayser, M, Kee, F, Keinanen Kiukaanniemi, S, Kiemeney, L, Kooner, J, Kooperberg, C, Koskinen, S, Kovacs, P, Kraja, A, Kumari, M, Kuusisto, J, Lakka, T, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lupoli, S, Madden, P, Männistö, S, Manunta, P, Marette, A, Matise, T, Mcknight, B, Meitinger, T, Moll, F, Montgomery, G, Morris, A, Murray, J, Nelis, M, Ohlsson, C, Oldehinkel, A, Ong, K, Ouwehand, W, Pasterkamp, G, Peters, A, Pramstaller, P, Price, J, Qi, L, Raitakari, O, Rankinen, T, Rao, D, Rice, T, Ritchie, M, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, M, Schwarz, P, Sebert, S, Sever, P, Shuldiner, A, Sinisalo, J, Steinthorsdottir, V, Stolk, R, Tardif, J, Tönjes, A, Tremblay, A, Tremoli, E, Virtamo, J, Vohl, M, Amouyel, P, Asselbergs, F, Assimes, T, Bochud, M, Boehm, B, Boerwinkle, E, Bottinger, E, Bouchard, C, Cauchi, S, Chambers, J, Chanock, S, Cooper, R, De Bakker, P, Dedoussis, G, Ferrucci, L, Franks, P, Froguel, P, Groop, L, Haiman, C, Hamsten, A, Hayes, M, Hui, J, Hunter, D, Hveem, K, Jukema, J, Kaplan, R, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, N, März, W, Melbye, M, Moebus, S, Munroe, P, Njølstad, I, Oostra, B, Pedersen, N, Perola, M, Pérusse, L, Peters, U, Powell, J, Power, C, Quertermous, T, Rauramaa, R, Reinmaa, E, Ridker, P, Rivadeneira, F, Rotter, J, Saaristo, T, Saleheen, D, Schlessinger, D, Slagboom, P, Snieder, H, Spector, T, Strauch, K, Stumvoll, M, Tuomilehto, J, Uusitupa, M, Van Der Harst, P, Völzke, H, Walker, M, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Zanen, P, Deloukas, P, Heid, I, Lindgren, C, Mohlke, K, Speliotes, E, Thorsteinsdottir, U, Barroso, I, Fox, C, North, K, Strachan, D, Beckmann, J, Berndt, S, Boehnke, M, Borecki, I, Mccarthy, M, Metspalu, A, Stefansson, K, Uitterlinden, A, Van Duijn, C, Franke, L, Willer, C, Price, A, Lettre, G, Loos, R, Weedon, M, Ingelsson, E, O'Connell, J, Abecasis, G, Chasman, D, Goddard, M, Visscher, P, Hirschhorn, J, Frayling, T, Frayling, T., BRAMBILLA, PAOLO, Wood, A, Esko, T, Yang, J, Vedantam, S, Pers, T, Gustafsson, S, Chu, A, Estrada, K, Luan, J, Kutalik, Z, Amin, N, Buchkovich, M, Croteau Chonka, D, Day, F, Duan, Y, Fall, T, Fehrmann, R, Ferreira, T, Jackson, A, Karjalainen, J, Lo, K, Locke, A, Mägi, R, Mihailov, E, Porcu, E, Randall, J, Scherag, A, Vinkhuyzen, A, Westra, H, Winkler, T, Workalemahu, T, Zhao, J, Absher, D, Albrecht, E, Anderson, D, Baron, J, Beekman, M, Demirkan, A, Ehret, G, Feenstra, B, Feitosa, M, Fischer, K, Fraser, R, Goel, A, Gong, J, Justice, A, Kanoni, S, Kleber, M, Kristiansson, K, Lim, U, Lotay, V, Lui, J, Mangino, M, Leach, I, Medina Gomez, C, Nalls, M, Nyholt, D, Palmer, C, Pasko, D, Pechlivanis, S, Prokopenko, I, Ried, J, Ripke, S, Shungin, D, Stancáková, A, Strawbridge, R, Sung, Y, Tanaka, T, Teumer, A, Trompet, S, Van Der Laan, S, Van Setten, J, Van Vliet Ostaptchouk, J, Wang, Z, Yengo, L, Zhang, W, Afzal, U, Ärnlöv, J, Arscott, G, Bandinelli, S, Barrett, A, Bellis, C, Bennett, A, Berne, C, Blüher, M, Bolton, J, Böttcher, Y, Boyd, H, Bruinenberg, M, Buckley, B, Buyske, S, Caspersen, I, Chines, P, Clarke, R, Claudi Boehm, S, Cooper, M, Daw, E, De Jong, P, Deelen, J, Delgado, G, Denny, J, Dhonukshe Rutten, R, Dimitriou, M, Doney, A, Dörr, M, Eklund, N, Eury, E, Folkersen, L, Garcia, M, Geller, F, Giedraitis, V, Go, A, Grallert, H, Grammer, T, Gräßler, J, Grönberg, H, De Groot, L, Groves, C, Haessler, J, Hall, P, Haller, T, Hallmans, G, Hannemann, A, Hartman, C, Hassinen, M, Hayward, C, Heard Costa, N, Helmer, Q, Hemani, G, Henders, A, Hillege, H, Hlatky, M, Hoffmann, W, Hoffmann, P, Holmen, O, Houwing Duistermaat, J, Illig, T, Isaacs, A, James, A, Jeff, J, Johansen, B, Johansson, Å, Jolley, J, Juliusdottir, T, Junttila, J, Kho, A, Kinnunen, L, Klopp, N, Kocher, T, Kratzer, W, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Lu, Y, Lyssenko, V, Magnusson, P, Mahajan, A, Maillard, M, Mcardle, W, Mckenzie, C, Mclachlan, S, Mclaren, P, Menni, C, Merger, S, Milani, L, Moayyeri, A, Monda, K, Morken, M, Müller, G, Müller Nurasyid, M, Musk, A, Narisu, N, Nauck, M, Nolte, I, Nöthen, M, Oozageer, L, Pilz, S, Rayner, N, Renstrom, F, Robertson, N, Rose, L, Roussel, R, Sanna, S, Scharnagl, H, Scholtens, S, Schumacher, F, Schunkert, H, Scott, R, Sehmi, J, Seufferlein, T, Shi, J, Silventoinen, K, Smit, J, Smith, A, Smolonska, J, Stanton, A, Stirrups, K, Stott, D, Stringham, H, Sundström, J, Swertz, M, Syvänen, A, Tayo, B, Thorleifsson, G, Tyrer, J, Van Dijk, S, Van Schoor, N, Van Der Velde, N, Van Heemst, D, Van Oort, F, Vermeulen, S, Verweij, N, Vonk, J, Waite, L, Waldenberger, M, Wennauer, R, Wilkens, L, Willenborg, C, Wilsgaard, T, Wojczynski, M, Wong, A, Wright, A, Zhang, Q, Arveiler, D, Bakker, S, Beilby, J, Bergman, R, Bergmann, S, Biffar, R, Blangero, J, Boomsma, D, Bornstein, S, Bovet, P, Brambilla, P, Brown, M, Campbell, H, Caulfield, M, Chakravarti, A, Collins, R, Collins, F, Crawford, D, Cupples, L, Danesh, J, De Faire, U, Den Ruijter, H, Erbel, R, Erdmann, J, Eriksson, J, Farrall, M, Ferrannini, E, Ferrières, J, Ford, I, Forouhi, N, Forrester, T, Gansevoort, R, Gejman, P, Gieger, C, Golay, A, Gottesman, O, Gudnason, V, Gyllensten, U, Haas, D, Hall, A, Harris, T, Hattersley, A, Heath, A, Hengstenberg, C, Hicks, A, Hindorff, L, Hingorani, A, Hofman, A, Hovingh, G, Humphries, S, Hunt, S, Hypponen, E, Jacobs, K, Jarvelin, M, Jousilahti, P, Jula, A, Kaprio, J, Kastelein, J, Kayser, M, Kee, F, Keinanen Kiukaanniemi, S, Kiemeney, L, Kooner, J, Kooperberg, C, Koskinen, S, Kovacs, P, Kraja, A, Kumari, M, Kuusisto, J, Lakka, T, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lupoli, S, Madden, P, Männistö, S, Manunta, P, Marette, A, Matise, T, Mcknight, B, Meitinger, T, Moll, F, Montgomery, G, Morris, A, Murray, J, Nelis, M, Ohlsson, C, Oldehinkel, A, Ong, K, Ouwehand, W, Pasterkamp, G, Peters, A, Pramstaller, P, Price, J, Qi, L, Raitakari, O, Rankinen, T, Rao, D, Rice, T, Ritchie, M, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, M, Schwarz, P, Sebert, S, Sever, P, Shuldiner, A, Sinisalo, J, Steinthorsdottir, V, Stolk, R, Tardif, J, Tönjes, A, Tremblay, A, Tremoli, E, Virtamo, J, Vohl, M, Amouyel, P, Asselbergs, F, Assimes, T, Bochud, M, Boehm, B, Boerwinkle, E, Bottinger, E, Bouchard, C, Cauchi, S, Chambers, J, Chanock, S, Cooper, R, De Bakker, P, Dedoussis, G, Ferrucci, L, Franks, P, Froguel, P, Groop, L, Haiman, C, Hamsten, A, Hayes, M, Hui, J, Hunter, D, Hveem, K, Jukema, J, Kaplan, R, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, N, März, W, Melbye, M, Moebus, S, Munroe, P, Njølstad, I, Oostra, B, Pedersen, N, Perola, M, Pérusse, L, Peters, U, Powell, J, Power, C, Quertermous, T, Rauramaa, R, Reinmaa, E, Ridker, P, Rivadeneira, F, Rotter, J, Saaristo, T, Saleheen, D, Schlessinger, D, Slagboom, P, Snieder, H, Spector, T, Strauch, K, Stumvoll, M, Tuomilehto, J, Uusitupa, M, Van Der Harst, P, Völzke, H, Walker, M, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Zanen, P, Deloukas, P, Heid, I, Lindgren, C, Mohlke, K, Speliotes, E, Thorsteinsdottir, U, Barroso, I, Fox, C, North, K, Strachan, D, Beckmann, J, Berndt, S, Boehnke, M, Borecki, I, Mccarthy, M, Metspalu, A, Stefansson, K, Uitterlinden, A, Van Duijn, C, Franke, L, Willer, C, Price, A, Lettre, G, Loos, R, Weedon, M, Ingelsson, E, O'Connell, J, Abecasis, G, Chasman, D, Goddard, M, Visscher, P, Hirschhorn, J, Frayling, T, Frayling, T., and BRAMBILLA, PAOLO
Abstract: Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated 1/42,000, 1/43,700 and 1/49,500 SNPs explained 1/421%, 1/424% and 1/429% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/I 2-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.
Published: 2014

9. Hostility in adolescents and adults

Author: University of Helsinki, Institute of Behavioural Sciences, University of Helsinki, Institute for Molecular Medicine Finland (FIMM), Merjonen, P., Keltikangas-Järvinen, L., Jokela, M., Seppälä, I., Lyytikäinen, L.-P., Pulkki-Råback, L., Kivimäki, M., Elovainio, M., Kettunen, J., Ripatti, S., Kähönen, M., Viikari, J., Palotie, A., Peltonen, L., Raitakari, O. T., Lehtimäki, T., University of Helsinki, Institute of Behavioural Sciences, University of Helsinki, Institute for Molecular Medicine Finland (FIMM), Merjonen, P., Keltikangas-Järvinen, L., Jokela, M., Seppälä, I., Lyytikäinen, L.-P., Pulkki-Råback, L., Kivimäki, M., Elovainio, M., Kettunen, J., Ripatti, S., Kähönen, M., Viikari, J., Palotie, A., Peltonen, L., Raitakari, O. T., and Lehtimäki, T.
Published: 2011

10. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Author: Ehret, GB, Munroe, PB, Rice, KM, Bochud, M, Johnson, AD, Chasman, DI, Smith, AV, Tobin, MD, Verwoert, GC, Hwang, S-J, Pihur, V, Vollenweider, P, O'Reilly, PF, Amin, N, Bragg-Gresham, JL, Teumer, A, Glazer, NL, Launer, L, Zhao, JH, Aulchenko, Y, Heath, S, Sober, S, Parsa, A, Luan, J, Arora, P, Dehghan, A, Zhang, F, Lucas, G, Hicks, AA, Jackson, AU, Peden, JF, Tanaka, T, Wild, SH, Rudan, I, Igl, W, Milaneschi, Y, Parker, AN, Fava, C, Chambers, JC, Fox, ER, Kumari, M, Go, MJ, van der Harst, P, Kao, WHL, Sjogren, M, Vinay, DG, Alexander, M, Tabara, Y, Shaw-Hawkins, S, Whincup, PH, Liu, Y, Shi, G, Kuusisto, J, Tayo, B, Seielstad, M, Sim, X, Khanh-Dung, HN, Lehtimaki, T, Matullo, G, Wu, Y, Gaunt, TR, Onland-Moret, NC, Cooper, MN, Platou, CGP, Org, E, Hardy, R, Dahgam, S, Palmen, J, Vitart, V, Braund, PS, Kuznetsova, T, Uiterwaal, CSPM, Adeyemo, A, Palmas, W, Campbell, H, Ludwig, B, Tomaszewski, M, Tzoulaki, I, Palmer, ND, Aspelund, T, Garcia, M, Chang, Y-PC, O'Connell, JR, Steinle, NI, Grobbee, DE, Arking, DE, Kardia, SL, Morrison, AC, Hernandez, D, Najjar, S, McArdle, WL, Hadley, D, Brown, MJ, Connell, JM, Hingorani, AD, Day, INM, Lawlor, DA, Beilby, JP, Lawrence, RW, Clarke, R, Hopewell, JC, Ongen, H, Dreisbach, AW, Li, Y, Young, JH, Bis, JC, Kahonen, M, Viikari, J, Adair, LS, Lee, NR, Chen, M-H, Olden, M, Pattaro, C, Bolton, JAH, Koettgen, A, Bergmann, S, Mooser, V, Chaturvedi, N, Frayling, TM, Islam, M, Jafar, TH, Erdmann, J, Kulkarni, SR, Bornstein, SR, Graessler, J, Groop, L, Voight, BF, Kettunen, J, Howard, P, Taylor, A, Guarrera, S, Ricceri, F, Emilsson, V, Plump, A, Barroso, IS, Khaw, K-T, Weder, AB, Hunt, SC, Sun, YV, Bergman, RN, Collins, FS, Bonnycastle, LL, Scott, LJ, Stringham, HM, Peltonen, L, Perola, M, Vartiainen, E, Brand, S-M, Staessen, JA, Wang, TJ, Burton, PR, Artigas, MS, Dong, Y, Snieder, H, Wang, X, Zhu, H, Lohman, KK, Rudock, ME, Heckbert, SR, Smith, NL, Wiggins, KL, Doumatey, A, Shriner, D, Veldre, G, Viigimaa, M, Kinra, S, Prabhakaran, D, Tripathy, V, Langefeld, CD, Rosengren, A, Thelle, DS, Corsi, AM, Singleton, A, Forrester, T, Hilton, G, McKenzie, CA, Salako, T, Iwai, N, Kita, Y, Ogihara, T, Ohkubo, T, Okamura, T, Ueshima, H, Umemura, S, Eyheramendy, S, Meitinger, T, Wichmann, H-E, Cho, YS, Kim, H-L, Lee, J-Y, Scott, J, Sehmi, JS, Zhang, W, Hedblad, B, Nilsson, P, Smith, GD, Wong, A, Narisu, N, Stancakova, A, Raffel, LJ, Yao, J, Kathiresan, S, O'Donnell, CJ, Schwartz, SM, Ikram, MA, Longstreth, WT, Mosley, TH, Seshadri, S, Shrine, NRG, Wain, LV, Morken, MA, Swift, AJ, Laitinen, J, Prokopenko, I, Zitting, P, Cooper, JA, Humphries, SE, Danesh, J, Rasheed, A, Goel, A, Hamsten, A, Watkins, H, Bakker, SJL, van Gilst, WH, Janipalli, CS, Mani, KR, Yajnik, CS, Hofman, A, Mattace-Raso, FUS, Oostra, BA, Demirkan, A, Isaacs, A, Rivadeneira, F, Lakatta, EG, Orru, M, Scuteri, A, Ala-Korpela, M, Kangas, AJ, Lyytikainen, L-P, Soininen, P, Tukiainen, T, Wurtz, P, Ong, RT-H, Doerr, M, Kroemer, HK, Voelker, U, Voelzke, H, Galan, P, Hercberg, S, Lathrop, M, Zelenika, D, Deloukas, P, Mangino, M, Spector, TD, Zhai, G, Meschia, JF, Nalls, MA, Sharma, P, Terzic, J, Kumar, MVK, Denniff, M, Zukowska-Szczechowska, E, Wagenknecht, LE, Fowkes, FGR, Charchar, FJ, Schwarz, PEH, Hayward, C, Guo, X, Rotimi, C, Bots, ML, Brand, E, Samani, NJ, Polasek, O, Talmud, PJ, Nyberg, F, Kuh, D, Laan, M, Hveem, K, Palmer, LJ, van der Schouw, YT, Casas, JP, Mohlke, KL, Vineis, P, Raitakari, O, Ganesh, SK, Wong, TY, Tai, ES, Cooper, RS, Laakso, M, Rao, DC, Harris, TB, Morris, RW, Dominiczak, AF, Kivimaki, M, Marmot, MG, Miki, T, Saleheen, D, Chandak, GR, Coresh, J, Navis, G, Salomaa, V, Han, B-G, Zhu, X, Kooner, JS, Melander, O, Ridker, PM, Bandinelli, S, Gyllensten, UB, Wright, AF, Wilson, JF, Ferrucci, L, Farrall, M, Tuomilehto, J, Pramstaller, PP, Elosua, R, Soranzo, N, Sijbrands, EJG, Altshuler, D, Loos, RJF, Shuldiner, AR, Gieger, C, Meneton, P, Uitterlinden, AG, Wareham, NJ, Gudnason, V, Rotter, JI, Rettig, R, Uda, M, Strachan, DP, Witteman, JCM, Hartikainen, A-L, Beckmann, JS, Boerwinkle, E, Vasan, RS, Boehnke, M, Larson, MG, Jarvelin, M-R, Psaty, BM, Abecasis, GR, Chakravarti, A, Elliott, P, van Duijn, CM, Newton-Cheh, C, Levy, D, Caulfield, MJ, Johnson, T, Ehret, GB, Munroe, PB, Rice, KM, Bochud, M, Johnson, AD, Chasman, DI, Smith, AV, Tobin, MD, Verwoert, GC, Hwang, S-J, Pihur, V, Vollenweider, P, O'Reilly, PF, Amin, N, Bragg-Gresham, JL, Teumer, A, Glazer, NL, Launer, L, Zhao, JH, Aulchenko, Y, Heath, S, Sober, S, Parsa, A, Luan, J, Arora, P, Dehghan, A, Zhang, F, Lucas, G, Hicks, AA, Jackson, AU, Peden, JF, Tanaka, T, Wild, SH, Rudan, I, Igl, W, Milaneschi, Y, Parker, AN, Fava, C, Chambers, JC, Fox, ER, Kumari, M, Go, MJ, van der Harst, P, Kao, WHL, Sjogren, M, Vinay, DG, Alexander, M, Tabara, Y, Shaw-Hawkins, S, Whincup, PH, Liu, Y, Shi, G, Kuusisto, J, Tayo, B, Seielstad, M, Sim, X, Khanh-Dung, HN, Lehtimaki, T, Matullo, G, Wu, Y, Gaunt, TR, Onland-Moret, NC, Cooper, MN, Platou, CGP, Org, E, Hardy, R, Dahgam, S, Palmen, J, Vitart, V, Braund, PS, Kuznetsova, T, Uiterwaal, CSPM, Adeyemo, A, Palmas, W, Campbell, H, Ludwig, B, Tomaszewski, M, Tzoulaki, I, Palmer, ND, Aspelund, T, Garcia, M, Chang, Y-PC, O'Connell, JR, Steinle, NI, Grobbee, DE, Arking, DE, Kardia, SL, Morrison, AC, Hernandez, D, Najjar, S, McArdle, WL, Hadley, D, Brown, MJ, Connell, JM, Hingorani, AD, Day, INM, Lawlor, DA, Beilby, JP, Lawrence, RW, Clarke, R, Hopewell, JC, Ongen, H, Dreisbach, AW, Li, Y, Young, JH, Bis, JC, Kahonen, M, Viikari, J, Adair, LS, Lee, NR, Chen, M-H, Olden, M, Pattaro, C, Bolton, JAH, Koettgen, A, Bergmann, S, Mooser, V, Chaturvedi, N, Frayling, TM, Islam, M, Jafar, TH, Erdmann, J, Kulkarni, SR, Bornstein, SR, Graessler, J, Groop, L, Voight, BF, Kettunen, J, Howard, P, Taylor, A, Guarrera, S, Ricceri, F, Emilsson, V, Plump, A, Barroso, IS, Khaw, K-T, Weder, AB, Hunt, SC, Sun, YV, Bergman, RN, Collins, FS, Bonnycastle, LL, Scott, LJ, Stringham, HM, Peltonen, L, Perola, M, Vartiainen, E, Brand, S-M, Staessen, JA, Wang, TJ, Burton, PR, Artigas, MS, Dong, Y, Snieder, H, Wang, X, Zhu, H, Lohman, KK, Rudock, ME, Heckbert, SR, Smith, NL, Wiggins, KL, Doumatey, A, Shriner, D, Veldre, G, Viigimaa, M, Kinra, S, Prabhakaran, D, Tripathy, V, Langefeld, CD, Rosengren, A, Thelle, DS, Corsi, AM, Singleton, A, Forrester, T, Hilton, G, McKenzie, CA, Salako, T, Iwai, N, Kita, Y, Ogihara, T, Ohkubo, T, Okamura, T, Ueshima, H, Umemura, S, Eyheramendy, S, Meitinger, T, Wichmann, H-E, Cho, YS, Kim, H-L, Lee, J-Y, Scott, J, Sehmi, JS, Zhang, W, Hedblad, B, Nilsson, P, Smith, GD, Wong, A, Narisu, N, Stancakova, A, Raffel, LJ, Yao, J, Kathiresan, S, O'Donnell, CJ, Schwartz, SM, Ikram, MA, Longstreth, WT, Mosley, TH, Seshadri, S, Shrine, NRG, Wain, LV, Morken, MA, Swift, AJ, Laitinen, J, Prokopenko, I, Zitting, P, Cooper, JA, Humphries, SE, Danesh, J, Rasheed, A, Goel, A, Hamsten, A, Watkins, H, Bakker, SJL, van Gilst, WH, Janipalli, CS, Mani, KR, Yajnik, CS, Hofman, A, Mattace-Raso, FUS, Oostra, BA, Demirkan, A, Isaacs, A, Rivadeneira, F, Lakatta, EG, Orru, M, Scuteri, A, Ala-Korpela, M, Kangas, AJ, Lyytikainen, L-P, Soininen, P, Tukiainen, T, Wurtz, P, Ong, RT-H, Doerr, M, Kroemer, HK, Voelker, U, Voelzke, H, Galan, P, Hercberg, S, Lathrop, M, Zelenika, D, Deloukas, P, Mangino, M, Spector, TD, Zhai, G, Meschia, JF, Nalls, MA, Sharma, P, Terzic, J, Kumar, MVK, Denniff, M, Zukowska-Szczechowska, E, Wagenknecht, LE, Fowkes, FGR, Charchar, FJ, Schwarz, PEH, Hayward, C, Guo, X, Rotimi, C, Bots, ML, Brand, E, Samani, NJ, Polasek, O, Talmud, PJ, Nyberg, F, Kuh, D, Laan, M, Hveem, K, Palmer, LJ, van der Schouw, YT, Casas, JP, Mohlke, KL, Vineis, P, Raitakari, O, Ganesh, SK, Wong, TY, Tai, ES, Cooper, RS, Laakso, M, Rao, DC, Harris, TB, Morris, RW, Dominiczak, AF, Kivimaki, M, Marmot, MG, Miki, T, Saleheen, D, Chandak, GR, Coresh, J, Navis, G, Salomaa, V, Han, B-G, Zhu, X, Kooner, JS, Melander, O, Ridker, PM, Bandinelli, S, Gyllensten, UB, Wright, AF, Wilson, JF, Ferrucci, L, Farrall, M, Tuomilehto, J, Pramstaller, PP, Elosua, R, Soranzo, N, Sijbrands, EJG, Altshuler, D, Loos, RJF, Shuldiner, AR, Gieger, C, Meneton, P, Uitterlinden, AG, Wareham, NJ, Gudnason, V, Rotter, JI, Rettig, R, Uda, M, Strachan, DP, Witteman, JCM, Hartikainen, A-L, Beckmann, JS, Boerwinkle, E, Vasan, RS, Boehnke, M, Larson, MG, Jarvelin, M-R, Psaty, BM, Abecasis, GR, Chakravarti, A, Elliott, P, van Duijn, CM, Newton-Cheh, C, Levy, D, Caulfield, MJ, and Johnson, T
Abstract: Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.
Published: 2011

11. Hundreds of variants clustered in genomic loci and biological pathways affect human height

Author: Allen, HL, Estrada, K, Lettre, G, Berndt, SI, Weedon, MN, Rivadeneira, F, Willer, CJ, Jackson, AU, Vedantam, S, Raychaudhuri, S, Ferreira, T, Wood, AR, Weyant, RJ, Segre, AV, Speliotes, EK, Wheeler, E, Soranzo, N, Park, J-H, Yang, J, Gudbjartsson, D, Heard-Costa, NL, Randall, JC, Qi, L, Smith, AV, Maegi, R, Pastinen, T, Liang, L, Heid, IM, Luan, J, Thorleifsson, G, Winkler, TW, Goddard, ME, Lo, KS, Palmer, C, Workalemahu, T, Aulchenko, YS, Johansson, A, Zillikens, MC, Feitosa, MF, Esko, T, Johnson, T, Ketkar, S, Kraft, P, Mangino, M, Prokopenko, I, Absher, D, Albrecht, E, Ernst, F, Glazer, NL, Hayward, C, Hottenga, J-J, Jacobs, KB, Knowles, JW, Kutalik, Z, Monda, KL, Polasek, O, Preuss, M, Rayner, NW, Robertson, NR, Steinthorsdottir, V, Tyrer, JP, Voight, BF, Wiklund, F, Xu, J, Zhao, JH, Nyholt, DR, Pellikka, N, Perola, M, Perry, JRB, Surakka, I, Tammesoo, M-L, Altmaier, EL, Amin, N, Aspelund, T, Bhangale, T, Boucher, G, Chasman, DI, Chen, C, Coin, L, Cooper, MN, Dixon, AL, Gibson, Q, Grundberg, E, Hao, K, Junttila, MJ, Kaplan, LM, Kettunen, J, Koenig, IR, Kwan, T, Lawrence, RW, Levinson, DF, Lorentzon, M, McKnight, B, Morris, AP, Mueller, M, Ngwa, JS, Purcell, S, Rafelt, S, Salem, RM, Salvi, E, Sanna, S, Shi, J, Sovio, U, Thompson, JR, Turchin, MC, Vandenput, L, Verlaan, DJ, Vitart, V, White, CC, Ziegler, A, Almgren, P, Balmforth, AJ, Campbell, H, Citterio, L, De Grandi, A, Dominiczak, A, Duan, J, Elliott, P, Elosua, R, Eriksson, JG, Freimer, NB, Geus, EJC, Glorioso, N, Haiqing, S, Hartikainen, A-L, Havulinna, AS, Hicks, AA, Hui, J, Igl, W, Illig, T, Jula, A, Kajantie, E, Kilpelaeinen, TO, Koiranen, M, Kolcic, I, Koskinen, S, Kovacs, P, Laitinen, J, Liu, J, Lokki, M-L, Marusic, A, Maschio, A, Meitinger, T, Mulas, A, Pare, G, Parker, AN, Peden, JF, Petersmann, A, Pichler, I, Pietilainen, KH, Pouta, A, Riddertrale, M, Rotter, JI, Sambrook, JG, Sanders, AR, Schmidt, CO, Sinisalo, J, Smit, JH, Stringham, HM, Walters, GB, Widen, E, Wild, SH, Willemsen, G, Zagato, L, Zgaga, L, Zitting, P, Alavere, H, Farrall, M, McArdle, WL, Nelis, M, Peters, MJ, Ripatti, S, vVan Meurs, JBJ, Aben, KK, Ardlie, KG, Beckmann, JS, Beilby, JP, Bergman, RN, Bergmann, S, Collins, FS, Cusi, D, den Heijer, M, Eiriksdottir, G, Gejman, PV, Hall, AS, Hamsten, A, Huikuri, HV, Iribarren, C, Kahonen, M, Kaprio, J, Kathiresan, S, Kiemeney, L, Kocher, T, Launer, LJ, Lehtimaki, T, Melander, O, Mosley, TH, Musk, AW, Nieminen, MS, O'Donnell, CJ, Ohlsson, C, Oostra, B, Palmer, LJ, Raitakari, O, Ridker, PM, Rioux, JD, Rissanen, A, Rivolta, C, Schunkert, H, Shuldiner, AR, Siscovick, DS, Stumvoll, M, Toenjes, A, Tuomilehto, J, van Ommen, G-J, Viikari, J, Heath, AC, Martin, NG, Montgomery, GW, Province, MA, Kayser, M, Arnold, AM, Atwood, LD, Boerwinkle, E, Chanock, SJ, Deloukas, P, Gieger, C, Gronberg, H, Hall, P, Hattersley, AT, Hengstenberg, C, Hoffman, W, Lathrop, GM, Salomaa, V, Schreiber, S, Uda, M, Waterworth, D, Wright, AF, Assimes, TL, Barroso, I, Hofman, A, Mohlke, KL, Boomsma, DI, Caulfield, MJ, Cupples, LA, Erdmann, J, Fox, CS, Gudnason, V, Gyllensten, U, Harris, TB, Hayes, RB, Jarvelin, M-R, Mooser, V, Munroe, PB, Ouwehand, WH, Penninx, BW, Pramstaller, PP, Quertermous, T, Rudan, I, Samani, NJ, Spector, TD, Voelzke, H, Watkins, H, Wilson, JF, Groop, LC, Haritunians, T, Hu, FB, Kaplan, RC, Metspalu, A, North, KE, Schlessinger, D, Wareham, NJ, Hunter, DJ, O'Connell, JR, Strachan, DP, Schadt, H-E, Thorsteinsdottir, U, Peltonen, L, Uitterlinden, AG, Visscher, PM, Chatterjee, N, Loos, RJF, Boehnke, M, McCarthy, MI, Ingelsson, E, Lindgren, CM, Abecasis, GR, Stefansson, K, Frayling, TM, Hirschhorn, JN, Allen, HL, Estrada, K, Lettre, G, Berndt, SI, Weedon, MN, Rivadeneira, F, Willer, CJ, Jackson, AU, Vedantam, S, Raychaudhuri, S, Ferreira, T, Wood, AR, Weyant, RJ, Segre, AV, Speliotes, EK, Wheeler, E, Soranzo, N, Park, J-H, Yang, J, Gudbjartsson, D, Heard-Costa, NL, Randall, JC, Qi, L, Smith, AV, Maegi, R, Pastinen, T, Liang, L, Heid, IM, Luan, J, Thorleifsson, G, Winkler, TW, Goddard, ME, Lo, KS, Palmer, C, Workalemahu, T, Aulchenko, YS, Johansson, A, Zillikens, MC, Feitosa, MF, Esko, T, Johnson, T, Ketkar, S, Kraft, P, Mangino, M, Prokopenko, I, Absher, D, Albrecht, E, Ernst, F, Glazer, NL, Hayward, C, Hottenga, J-J, Jacobs, KB, Knowles, JW, Kutalik, Z, Monda, KL, Polasek, O, Preuss, M, Rayner, NW, Robertson, NR, Steinthorsdottir, V, Tyrer, JP, Voight, BF, Wiklund, F, Xu, J, Zhao, JH, Nyholt, DR, Pellikka, N, Perola, M, Perry, JRB, Surakka, I, Tammesoo, M-L, Altmaier, EL, Amin, N, Aspelund, T, Bhangale, T, Boucher, G, Chasman, DI, Chen, C, Coin, L, Cooper, MN, Dixon, AL, Gibson, Q, Grundberg, E, Hao, K, Junttila, MJ, Kaplan, LM, Kettunen, J, Koenig, IR, Kwan, T, Lawrence, RW, Levinson, DF, Lorentzon, M, McKnight, B, Morris, AP, Mueller, M, Ngwa, JS, Purcell, S, Rafelt, S, Salem, RM, Salvi, E, Sanna, S, Shi, J, Sovio, U, Thompson, JR, Turchin, MC, Vandenput, L, Verlaan, DJ, Vitart, V, White, CC, Ziegler, A, Almgren, P, Balmforth, AJ, Campbell, H, Citterio, L, De Grandi, A, Dominiczak, A, Duan, J, Elliott, P, Elosua, R, Eriksson, JG, Freimer, NB, Geus, EJC, Glorioso, N, Haiqing, S, Hartikainen, A-L, Havulinna, AS, Hicks, AA, Hui, J, Igl, W, Illig, T, Jula, A, Kajantie, E, Kilpelaeinen, TO, Koiranen, M, Kolcic, I, Koskinen, S, Kovacs, P, Laitinen, J, Liu, J, Lokki, M-L, Marusic, A, Maschio, A, Meitinger, T, Mulas, A, Pare, G, Parker, AN, Peden, JF, Petersmann, A, Pichler, I, Pietilainen, KH, Pouta, A, Riddertrale, M, Rotter, JI, Sambrook, JG, Sanders, AR, Schmidt, CO, Sinisalo, J, Smit, JH, Stringham, HM, Walters, GB, Widen, E, Wild, SH, Willemsen, G, Zagato, L, Zgaga, L, Zitting, P, Alavere, H, Farrall, M, McArdle, WL, Nelis, M, Peters, MJ, Ripatti, S, vVan Meurs, JBJ, Aben, KK, Ardlie, KG, Beckmann, JS, Beilby, JP, Bergman, RN, Bergmann, S, Collins, FS, Cusi, D, den Heijer, M, Eiriksdottir, G, Gejman, PV, Hall, AS, Hamsten, A, Huikuri, HV, Iribarren, C, Kahonen, M, Kaprio, J, Kathiresan, S, Kiemeney, L, Kocher, T, Launer, LJ, Lehtimaki, T, Melander, O, Mosley, TH, Musk, AW, Nieminen, MS, O'Donnell, CJ, Ohlsson, C, Oostra, B, Palmer, LJ, Raitakari, O, Ridker, PM, Rioux, JD, Rissanen, A, Rivolta, C, Schunkert, H, Shuldiner, AR, Siscovick, DS, Stumvoll, M, Toenjes, A, Tuomilehto, J, van Ommen, G-J, Viikari, J, Heath, AC, Martin, NG, Montgomery, GW, Province, MA, Kayser, M, Arnold, AM, Atwood, LD, Boerwinkle, E, Chanock, SJ, Deloukas, P, Gieger, C, Gronberg, H, Hall, P, Hattersley, AT, Hengstenberg, C, Hoffman, W, Lathrop, GM, Salomaa, V, Schreiber, S, Uda, M, Waterworth, D, Wright, AF, Assimes, TL, Barroso, I, Hofman, A, Mohlke, KL, Boomsma, DI, Caulfield, MJ, Cupples, LA, Erdmann, J, Fox, CS, Gudnason, V, Gyllensten, U, Harris, TB, Hayes, RB, Jarvelin, M-R, Mooser, V, Munroe, PB, Ouwehand, WH, Penninx, BW, Pramstaller, PP, Quertermous, T, Rudan, I, Samani, NJ, Spector, TD, Voelzke, H, Watkins, H, Wilson, JF, Groop, LC, Haritunians, T, Hu, FB, Kaplan, RC, Metspalu, A, North, KE, Schlessinger, D, Wareham, NJ, Hunter, DJ, O'Connell, JR, Strachan, DP, Schadt, H-E, Thorsteinsdottir, U, Peltonen, L, Uitterlinden, AG, Visscher, PM, Chatterjee, N, Loos, RJF, Boehnke, M, McCarthy, MI, Ingelsson, E, Lindgren, CM, Abecasis, GR, Stefansson, K, Frayling, TM, and Hirschhorn, JN
Abstract: Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can ide
Published: 2010

12. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

Author: Speliotes, EK, Willer, CJ, Berndt, SI, Monda, KL, Thorleifsson, G, Jackson, AU, Allen, HL, Lindgren, CM, Luan, J, Maegi, R, Randall, JC, Vedantam, S, Winkler, TW, Qi, L, Workalemahu, T, Heid, IM, Steinthorsdottir, V, Stringham, HM, Weedon, MN, Wheeler, E, Wood, AR, Ferreira, T, Weyant, RJ, Segre, AV, Estrada, K, Liang, L, Nemesh, J, Park, J-H, Gustafsson, S, Kilpelaenen, TO, Yang, J, Bouatia-Naji, N, Esko, T, Feitosa, MF, Kutalik, Z, Mangino, M, Raychaudhuri, S, Scherag, A, Smith, AV, Welch, R, Zhao, JH, Aben, KK, Absher, DM, Amin, N, Dixon, AL, Fisher, E, Glazer, NL, Goddard, ME, Heard-Costa, NL, Hoesel, V, Hottenga, J-J, Johansson, A, Johnson, T, Ketkar, S, Lamina, C, Li, S, Moffatt, MF, Myers, RH, Narisu, N, Perry, JRB, Peters, MJ, Preuss, M, Ripatti, S, Rivadeneira, F, Sandholt, C, Scott, LJ, Timpson, NJ, Tyrer, JP, van Wingerden, S, Watanabe, RM, White, CC, Wiklund, F, Barlassina, C, Chasman, DI, Cooper, MN, Jansson, J-O, Lawrence, RW, Pellikka, N, Prokopenko, I, Shi, J, Thiering, E, Alavere, H, Alibrandi, MTS, Almgren, P, Arnold, AM, Aspelund, T, Atwood, LD, Balkau, B, Balmforth, AJ, Bennett, AJ, Ben-Shlomo, Y, Bergman, RN, Bergmann, S, Biebermann, H, Blakemore, AIF, Boes, T, Bonnycastle, LL, Bornstein, SR, Brown, MJ, Buchanan, TA, Busonero, F, Campbell, H, Cappuccio, FP, Cavalcanti-Proenca, C, Chen, Y-DI, Chen, C-M, Chines, PS, Clarke, R, Coin, L, Connell, J, Day, INM, den Heijer, M, Duan, J, Ebrahim, S, Elliott, P, Elosua, R, Eiriksdottir, G, Erdos, MR, Eriksson, JG, Facheris, MF, Felix, SB, Fischer-Posovszky, P, Folsom, AR, Friedrich, N, Freimer, NB, Fu, M, Gaget, S, Gejman, PV, Geus, EJC, Gieger, C, Gjesing, AP, Goel, A, Goyette, P, Grallert, H, Graessler, J, Greenawalt, DM, Groves, CJ, Gudnason, V, Guiducci, C, Hartikainen, A-L, Hassanali, N, Hall, AS, Havulinna, AS, Hayward, C, Heath, AC, Hengstenberg, C, Hicks, AA, Hinney, A, Hofman, A, Homuth, G, Hui, J, Igl, W, Iribarren, C, Isomaa, B, Jacobs, KB, Jarick, I, Jewell, E, John, U, Jorgensen, T, Jousilahti, P, Jula, A, Kaakinen, M, Kajantie, E, Kaplan, LM, Kathiresan, S, Kettunen, J, Kinnunen, L, Knowles, JW, Kolcic, I, Koenig, IR, Koskinen, S, Kovacs, P, Kuusisto, J, Kraft, P, Kvaloy, K, Laitinen, J, Lantieri, O, Lanzani, C, Launer, LJ, Lecoeur, C, Lehtimaeki, T, Lettre, G, Liu, J, Lokki, M-L, Lorentzon, M, Luben, RN, Ludwig, B, Manunta, P, Marek, D, Marre, M, Martin, NG, McArdle, WL, McCarthy, A, McKnight, B, Meitinger, T, Melander, O, Meyre, D, Midthjell, K, Montgomery, GW, Morken, MA, Morris, AP, Mulic, R, Ngwa, JS, Nelis, M, Neville, MJ, Nyholt, DR, O'Donnell, CJ, O'Rahilly, S, Ong, KK, Oostra, B, Pare, G, Parker, AN, Perola, M, Pichler, I, Pietilaeinen, KH, Platou, CGP, Polasek, O, Pouta, A, Rafelt, S, Raitakari, O, Rayner, NW, Ridderstrale, M, Rief, W, Ruokonen, A, Robertson, NR, Rzehak, P, Salomaa, V, Sanders, AR, Sandhu, MS, Sanna, S, Saramies, J, Savolainen, MJ, Scherag, S, Schipf, S, Schreiber, S, Schunkert, H, Silander, K, Sinisalo, J, Siscovick, DS, Smit, JH, Soranzo, N, Sovio, U, Stephens, J, Surakka, I, Swift, AJ, Tammesoo, M-L, Tardif, J-C, Teder-Laving, M, Teslovich, TM, Thompson, JR, Thomson, B, Toenjes, A, Tuomi, T, van Meurs, JBJ, van Ommen, G-J, Vatin, V, Viikari, J, Visvikis-Siest, S, Vitart, V, Vogel, CIG, Voight, BF, Waite, LL, Wallaschofski, H, Walters, GB, Widen, E, Wiegand, S, Wild, SH, Willemsen, G, Witte, DR, Witteman, JC, Xu, J, Zhang, Q, Zgaga, L, Ziegler, A, Zitting, P, Beilby, JP, Farooqi, IS, Hebebrand, J, Huikuri, HV, James, AL, Kaehoenen, M, Levinson, DF, Macciardi, F, Nieminen, MS, Ohlsson, C, Palmer, LJ, Ridker, PM, Stumvoll, M, Beckmann, JS, Boeing, H, Boerwinkle, E, Boomsma, DI, Caulfield, MJ, Chanock, SJ, Collins, FS, Cupples, LA, Smith, GD, Erdmann, J, Froguel, P, Greonberg, H, Gyllensten, U, Hall, P, Hansen, T, Harris, TB, Hattersley, AT, Hayes, RB, Heinrich, J, Hu, FB, Hveem, K, Illig, T, Jarvelin, M-R, Kaprio, J, Karpe, F, Khaw, K-T, Kiemeney, LA, Krude, H, Laakso, M, Lawlor, DA, Metspalu, A, Munroe, PB, Ouwehand, WH, Pedersen, O, Penninx, BW, Peters, A, Pramstaller, PP, Quertermous, T, Reinehr, T, Rissanen, A, Rudan, I, Samani, NJ, Schwarz, PEH, Shuldiner, AR, Spector, TD, Tuomilehto, J, Uda, M, Uitterlinden, A, Valle, TT, Wabitsch, M, Waeber, G, Wareham, NJ, Watkins, H, Wilson, JF, Wright, AF, Zillikens, MC, Chatterjee, N, McCarroll, SA, Purcell, S, Schadt, EE, Visscher, PM, Assimes, TL, Borecki, IB, Deloukas, P, Fox, CS, Groop, LC, Haritunians, T, Hunter, DJ, Kaplan, RC, Mohlke, KL, O'Connell, JR, Peltonen, L, Schlessinger, D, Strachan, DP, van Duijn, CM, Wichmann, H-E, Frayling, TM, Thorsteinsdottir, U, Abecasis, GR, Barroso, I, Boehnke, M, Stefansson, K, North, KE, McCarthy, MI, Hirschhorn, JN, Ingelsson, E, Loos, RJF, Speliotes, EK, Willer, CJ, Berndt, SI, Monda, KL, Thorleifsson, G, Jackson, AU, Allen, HL, Lindgren, CM, Luan, J, Maegi, R, Randall, JC, Vedantam, S, Winkler, TW, Qi, L, Workalemahu, T, Heid, IM, Steinthorsdottir, V, Stringham, HM, Weedon, MN, Wheeler, E, Wood, AR, Ferreira, T, Weyant, RJ, Segre, AV, Estrada, K, Liang, L, Nemesh, J, Park, J-H, Gustafsson, S, Kilpelaenen, TO, Yang, J, Bouatia-Naji, N, Esko, T, Feitosa, MF, Kutalik, Z, Mangino, M, Raychaudhuri, S, Scherag, A, Smith, AV, Welch, R, Zhao, JH, Aben, KK, Absher, DM, Amin, N, Dixon, AL, Fisher, E, Glazer, NL, Goddard, ME, Heard-Costa, NL, Hoesel, V, Hottenga, J-J, Johansson, A, Johnson, T, Ketkar, S, Lamina, C, Li, S, Moffatt, MF, Myers, RH, Narisu, N, Perry, JRB, Peters, MJ, Preuss, M, Ripatti, S, Rivadeneira, F, Sandholt, C, Scott, LJ, Timpson, NJ, Tyrer, JP, van Wingerden, S, Watanabe, RM, White, CC, Wiklund, F, Barlassina, C, Chasman, DI, Cooper, MN, Jansson, J-O, Lawrence, RW, Pellikka, N, Prokopenko, I, Shi, J, Thiering, E, Alavere, H, Alibrandi, MTS, Almgren, P, Arnold, AM, Aspelund, T, Atwood, LD, Balkau, B, Balmforth, AJ, Bennett, AJ, Ben-Shlomo, Y, Bergman, RN, Bergmann, S, Biebermann, H, Blakemore, AIF, Boes, T, Bonnycastle, LL, Bornstein, SR, Brown, MJ, Buchanan, TA, Busonero, F, Campbell, H, Cappuccio, FP, Cavalcanti-Proenca, C, Chen, Y-DI, Chen, C-M, Chines, PS, Clarke, R, Coin, L, Connell, J, Day, INM, den Heijer, M, Duan, J, Ebrahim, S, Elliott, P, Elosua, R, Eiriksdottir, G, Erdos, MR, Eriksson, JG, Facheris, MF, Felix, SB, Fischer-Posovszky, P, Folsom, AR, Friedrich, N, Freimer, NB, Fu, M, Gaget, S, Gejman, PV, Geus, EJC, Gieger, C, Gjesing, AP, Goel, A, Goyette, P, Grallert, H, Graessler, J, Greenawalt, DM, Groves, CJ, Gudnason, V, Guiducci, C, Hartikainen, A-L, Hassanali, N, Hall, AS, Havulinna, AS, Hayward, C, Heath, AC, Hengstenberg, C, Hicks, AA, Hinney, A, Hofman, A, Homuth, G, Hui, J, Igl, W, Iribarren, C, Isomaa, B, Jacobs, KB, Jarick, I, Jewell, E, John, U, Jorgensen, T, Jousilahti, P, Jula, A, Kaakinen, M, Kajantie, E, Kaplan, LM, Kathiresan, S, Kettunen, J, Kinnunen, L, Knowles, JW, Kolcic, I, Koenig, IR, Koskinen, S, Kovacs, P, Kuusisto, J, Kraft, P, Kvaloy, K, Laitinen, J, Lantieri, O, Lanzani, C, Launer, LJ, Lecoeur, C, Lehtimaeki, T, Lettre, G, Liu, J, Lokki, M-L, Lorentzon, M, Luben, RN, Ludwig, B, Manunta, P, Marek, D, Marre, M, Martin, NG, McArdle, WL, McCarthy, A, McKnight, B, Meitinger, T, Melander, O, Meyre, D, Midthjell, K, Montgomery, GW, Morken, MA, Morris, AP, Mulic, R, Ngwa, JS, Nelis, M, Neville, MJ, Nyholt, DR, O'Donnell, CJ, O'Rahilly, S, Ong, KK, Oostra, B, Pare, G, Parker, AN, Perola, M, Pichler, I, Pietilaeinen, KH, Platou, CGP, Polasek, O, Pouta, A, Rafelt, S, Raitakari, O, Rayner, NW, Ridderstrale, M, Rief, W, Ruokonen, A, Robertson, NR, Rzehak, P, Salomaa, V, Sanders, AR, Sandhu, MS, Sanna, S, Saramies, J, Savolainen, MJ, Scherag, S, Schipf, S, Schreiber, S, Schunkert, H, Silander, K, Sinisalo, J, Siscovick, DS, Smit, JH, Soranzo, N, Sovio, U, Stephens, J, Surakka, I, Swift, AJ, Tammesoo, M-L, Tardif, J-C, Teder-Laving, M, Teslovich, TM, Thompson, JR, Thomson, B, Toenjes, A, Tuomi, T, van Meurs, JBJ, van Ommen, G-J, Vatin, V, Viikari, J, Visvikis-Siest, S, Vitart, V, Vogel, CIG, Voight, BF, Waite, LL, Wallaschofski, H, Walters, GB, Widen, E, Wiegand, S, Wild, SH, Willemsen, G, Witte, DR, Witteman, JC, Xu, J, Zhang, Q, Zgaga, L, Ziegler, A, Zitting, P, Beilby, JP, Farooqi, IS, Hebebrand, J, Huikuri, HV, James, AL, Kaehoenen, M, Levinson, DF, Macciardi, F, Nieminen, MS, Ohlsson, C, Palmer, LJ, Ridker, PM, Stumvoll, M, Beckmann, JS, Boeing, H, Boerwinkle, E, Boomsma, DI, Caulfield, MJ, Chanock, SJ, Collins, FS, Cupples, LA, Smith, GD, Erdmann, J, Froguel, P, Greonberg, H, Gyllensten, U, Hall, P, Hansen, T, Harris, TB, Hattersley, AT, Hayes, RB, Heinrich, J, Hu, FB, Hveem, K, Illig, T, Jarvelin, M-R, Kaprio, J, Karpe, F, Khaw, K-T, Kiemeney, LA, Krude, H, Laakso, M, Lawlor, DA, Metspalu, A, Munroe, PB, Ouwehand, WH, Pedersen, O, Penninx, BW, Peters, A, Pramstaller, PP, Quertermous, T, Reinehr, T, Rissanen, A, Rudan, I, Samani, NJ, Schwarz, PEH, Shuldiner, AR, Spector, TD, Tuomilehto, J, Uda, M, Uitterlinden, A, Valle, TT, Wabitsch, M, Waeber, G, Wareham, NJ, Watkins, H, Wilson, JF, Wright, AF, Zillikens, MC, Chatterjee, N, McCarroll, SA, Purcell, S, Schadt, EE, Visscher, PM, Assimes, TL, Borecki, IB, Deloukas, P, Fox, CS, Groop, LC, Haritunians, T, Hunter, DJ, Kaplan, RC, Mohlke, KL, O'Connell, JR, Peltonen, L, Schlessinger, D, Strachan, DP, van Duijn, CM, Wichmann, H-E, Frayling, TM, Thorsteinsdottir, U, Abecasis, GR, Barroso, I, Boehnke, M, Stefansson, K, North, KE, McCarthy, MI, Hirschhorn, JN, Ingelsson, E, and Loos, RJF
Abstract: Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10⁻⁸), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
Published: 2010

13. Associations of active commuting to school in childhood and physical activity in adulthood.

Author: Kaseva K, Lounassalo I, Yang X, Kukko T, Hakonen H, Kulmala J, Pahkala K, Rovio S, Hirvensalo M, Raitakari O, Tammelin TH, and Salin K
Subjects: Adolescent, Humans, Schools, Surveys and Questionnaires, Transportation, Exercise, Motor Activity
Abstract: This study examined whether active commuting to school in childhood and adolescence predicted active commuting to work and overall physical activity (PA) in adulthood. Participants from the Young Finns Study (N = 2436) were aged 9-18 years in 1980 and followed up until 2018/2020. Their commuting modes to school were assessed with a self-reported questionnaire in 1980. Adulthood PA was assessed through self-reports regarding commuting modes to work (2001-2018), leisure-time physical activity (LTPA) (2001-2018), and objectively measured daily steps (2007-2018/2020). Associations between childhood commuting and adulthood PA were evaluated using regression analyses and multilevel models. Demographic, socioeconomic and environmental covariates were adjusted for in the analyses. Active commuting to school in childhood contributed favourably to LTPA in 2001 (B = .38, p < .001), in 2007 (B = .35, p < .001), and in 2018 (B = .28, p < .01). Active commuting in childhood was associated with higher number of daily aerobic steps (B = 299.00, p = .03) and daily aerobic steps during weekdays in 2011 (B = 312.15, p = .03). In 2018, active commuting associated favourably with daily aerobic steps (B = 370.42, p < .01), daily aerobic steps during weekdays (B = 347.65, p = .01), daily steps during weekends (B = 628.49, p = .02), and daily aerobic steps during weekends (B = 402.69, p = .03). Covariate adjustments attenuated the associations excluding the one between active commuting and LTPA in 2007 (B = .36, p = .01) and daily steps during weekends in 2018 (B = 782.25, p = .04). Active commuting to school in childhood might be one of the PA modes that contribute to PA in adulthood and is therefore encouraged to be promoted from an early age., (© 2023. The Author(s).)
Published: 2023
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14. A new blood based epigenetic age predictor for adolescents and young adults.

Author: Aanes H, Bleka Ø, Dahlberg PS, Carm KT, Lehtimäki T, Raitakari O, Kähönen M, Hurme M, and Rolseth V
Subjects: Child, Humans, Young Adult, Adolescent, CpG Islands genetics, DNA Methylation, Biomarkers, Epigenomics methods, Epigenesis, Genetic, Aging genetics
Abstract: Children have special rights for protection compared to adults in our society. However, more than 1/4 of children globally have no documentation of their date of birth. Hence, there is a pressing need to develop biological methods for chronological age prediction, robust to differences in genetics, psychosocial events and physical living conditions. At present, DNA methylation is the most promising biological biomarker applied for age assessment. The human genome contains around 28 million DNA methylation sites, many of which change with age. Several epigenetic clocks accurately predict chronological age using methylation levels at age associated GpG-sites. However, variation in DNA methylation increases with age, and there is no epigenetic clock specifically designed for adolescents and young adults. Here we present a novel age Predictor for Adolescents and Young Adults (PAYA), using 267 CpG methylation sites to assess the chronological age of adolescents and young adults. We compared different preprocessing approaches and investigated the effect on prediction performance of the epigenetic clock. We evaluated performance using an independent validation data set consisting of 18-year-old individuals, where we obtained a median absolute deviation of just below 0.7 years. This tool may be helpful in age assessment of adolescents and young adults. However, there is a need to investigate the robustness of the age predictor across geographical and disease populations as well as environmental effects., (© 2023. The Author(s).)
Published: 2023
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15. Long-term residential sunlight exposure associated with cognitive function among adults residing in Finland.

Author: Komulainen K, Hakulinen C, Lipsanen J, Partonen T, Pulkki-Råback L, Kähönen M, Virtanen M, Ruuhela R, Raitakari O, Rovio S, and Elovainio M
Subjects: Adult, Humans, Finland epidemiology, Executive Function, Memory, Sunlight, Cognition
Abstract: While sunlight may influence cognitive function through several pathways, associations of residential sunlight exposure with cognitive function are not well known. We evaluated associations of long-term residential sunlight exposure with cognitive function among a representative cohort of 1838 Finnish adults residing in Finland who underwent comprehensive cognitive assessment in midlife. We linked daily recordings of global solar radiation to study participants using residential information and calculated the average daily residential exposure to sunlight for four exposure time intervals: 2 months, 1 year, 2 years and 5 years prior to the date of the cognition assessment. Associations of the residential sunlight exposure with cognitive function were assessed using linear regression analyses adjusting for season, sex, age, and individual- and neighborhood-level socioeconomic characteristics. Greater average residential sunlight exposure over 2 and 5 years prior to the cognitive function assessment was associated with better global cognitive function (b = 0.13, 95% CI = 0.01, 0.25; b = 0.17, 95% CI = 0.05, 0.29, per 1 MJ/m 2 difference in sunlight exposure), while no associations with global cognitive function were observed at shorter exposure time intervals. In domain-specific analyses, greater residential exposure to sunlight over 1, 2 and 5 years prior to the cognitive function assessment was associated with better performance on new learning and visual memory (b = 0.10, 95% CI = 0.00, 0.20; b = 0.16, 95% CI = 0.04, 0.28; b = 0.19, 95% CI = 0.08, 0.31) and sustained attention (b = 0.15, 95% CI = 0.05, 0.25; b = 0.18, 95% CI = 0.06, 0.30; b = 0.17, 95% CI = 0.05, 0.29), but worse performance on reaction time (b = - 0.12, 95% CI = - 0.22, - 0.02; b = -0.15, 95% CI = - 0.28, - 0.02; b = - 0.18, 95% CI = - 0.30, - 0.05). Residential sunlight exposure was not associated with executive function. These findings suggest long-term residential sunlight exposure may be an environmental factor influencing cognitive function among a cognitively healthy cohort residing in Northern Europe. Further studies in populations residing in different geographical locations are needed., (© 2022. The Author(s).)
Published: 2022
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16. Adulthood blood levels of hsa-miR-29b-3p associate with preterm birth and adult metabolic and cognitive health.

Author: Marttila S, Rovio S, Mishra PP, Seppälä I, Lyytikäinen LP, Juonala M, Waldenberger M, Oksala N, Ala-Korpela M, Harville E, Hutri-Kähönen N, Kähönen M, Raitakari O, Lehtimäki T, and Raitoharju E
Subjects: Adolescent, Adult, Child, Child, Preschool, Cognitive Dysfunction blood, Cognitive Dysfunction genetics, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 genetics, Female, Finland epidemiology, Follow-Up Studies, Gene Expression Profiling, Humans, Infant, Newborn, Male, Metabolic Diseases blood, Metabolic Diseases genetics, Middle Aged, Pregnancy, Prognosis, Signal Transduction, Biomarkers blood, Cognitive Dysfunction epidemiology, Diabetes Mellitus, Type 2 epidemiology, Metabolic Diseases epidemiology, MicroRNAs genetics, Premature Birth physiopathology
Abstract: Preterm birth (PTB) is associated with increased risk of type 2 diabetes and neurocognitive impairment later in life. We analyzed for the first time the associations of PTB with blood miRNA levels in adulthood. We also investigated the relationship of PTB associated miRNAs and adulthood phenotypes previously linked with premature birth. Blood MicroRNA profiling, genome-wide gene expression analysis, computer-based cognitive testing battery (CANTAB) and serum NMR metabolomics were performed for Young Finns Study subjects (aged 34-49 years, full-term n = 682, preterm n = 84). Preterm birth (vs. full-term) was associated with adulthood levels of hsa-miR-29b-3p in a fully adjusted regression model (p = 1.90 × 10 -4 , FDR = 0.046). The levels of hsa-miR-29b-3p were down-regulated in subjects with PTB with appropriate birthweight for gestational age (p = 0.002, fold change [FC] = - 1.20) and specifically in PTB subjects with small birthweight for gestational age (p = 0.095, FC = - 1.39) in comparison to individuals born full term. Hsa-miR-29b-3p levels correlated with the expressions of its target-mRNAs BCL11A and CS and the gene set analysis results indicated a target-mRNA driven association between hsa-miR-29b-3p levels and Alzheimer's disease, Parkinson's disease, Insulin signaling and Regulation of Actin Cytoskeleton pathway expression. The level of hsa-miR-29b-3p was directly associated with visual processing and sustained attention in CANTAB test and inversely associated with serum levels of VLDL subclass component and triglyceride levels. In conlcusion, adult blood levels of hsa-miR-29b-3p were lower in subjects born preterm. Hsa-miR-29b-3p associated with cognitive function and may be linked with adulthood morbidities in subjects born preterm, possibly through regulation of gene sets related to neurodegenerative diseases and insulin signaling as well as VLDL and triglyceride metabolism.
Published: 2021
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17. Examining the effect of mitochondrial DNA variants on blood pressure in two Finnish cohorts.

Author: Laaksonen J, Mishra PP, Seppälä I, Lyytikäinen LP, Raitoharju E, Mononen N, Lepistö M, Almusa H, Ellonen P, Hutri-Kähönen N, Juonala M, Raitakari O, Kähönen M, Salonen JT, and Lehtimäki T
Subjects: Adult, Blood Pressure, Cohort Studies, DNA, Mitochondrial analysis, Female, Finland epidemiology, Genome-Wide Association Study, Genotype, Humans, Hypertension genetics, Male, Middle Aged, Phenotype, Risk Factors, DNA, Mitochondrial genetics, Genome, Mitochondrial, Hypertension epidemiology, Mitochondria genetics, Polymorphism, Single Nucleotide
Abstract: High blood pressure (BP) is a major risk factor for many noncommunicable diseases. The effect of mitochondrial DNA single-nucleotide polymorphisms (mtSNPs) on BP is less known than that of nuclear SNPs. We investigated the mitochondrial genetic determinants of systolic, diastolic, and mean arterial BP. MtSNPs were determined from peripheral blood by sequencing or with genome-wide association study SNP arrays in two independent Finnish cohorts, the Young Finns Study and the Finnish Cardiovascular Study, respectively. In total, over 4200 individuals were included. The effects of individual common mtSNPs, with an additional focus on sex-specificity, and aggregates of rare mtSNPs grouped by mitochondrial genes were evaluated by meta-analysis of linear regression and a sequence kernel association test, respectively. We accounted for the predicted pathogenicity of the rare variants within protein-encoding and the tRNA regions. In the meta-analysis of 87 common mtSNPs, we did not observe significant associations with any of the BP traits. Sex-specific and rare-variant analyses did not pinpoint any significant associations either. Our results are in agreement with several previous studies suggesting that mtDNA variation does not have a significant role in the regulation of BP. Future studies might need to reconsider the mechanisms thought to link mtDNA with hypertension.
Published: 2021
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18. HDL cholesterol efflux capacity is inversely associated with subclinical cardiovascular risk markers in young adults: The cardiovascular risk in Young Finns study.

Author: Hunjadi M, Lamina C, Kahler P, Bernscherer T, Viikari J, Lehtimäki T, Kähönen M, Hurme M, Juonala M, Taittonen L, Laitinen T, Jokinen E, Tossavainen P, Hutri-Kähönen N, Raitakari O, and Ritsch A
Subjects: Adult, Atherosclerosis blood, Atherosclerosis diagnostic imaging, Biomarkers blood, Cardiovascular Diseases blood, Cardiovascular Diseases diagnostic imaging, Carotid Arteries diagnostic imaging, Carotid Intima-Media Thickness, Elastic Modulus, Female, Finland, Follow-Up Studies, Humans, Incidence, Male, Risk Assessment, Ultrasonography, Young Adult, Atherosclerosis epidemiology, Cardiovascular Diseases epidemiology, Cholesterol, HDL blood, Heart Disease Risk Factors
Abstract: The atherogenic process begins already in childhood and progresses to symptomatic condition with age. We investigated the association of cholesterol efflux capacity (CEC) and vascular markers of subclinical atherosclerosis in healthy, young adults. CEC was determined in 2282 participants of the Young Finns study using cAMP treated 3 H-cholesterol-labeled J774 cells. The CEC was correlated to baseline and 6-year follow-up data of cardiovascular risk factors and ultrasound measurements of arterial structure and function. CEC was higher in women, correlated with total cholesterol, HDL-C, and apolipoprotein A-I, but not with LDL-C or apolipoprotein B. Compared to the lowest CEC quartile, the highest CEC quartile was significantly associated with high CRP levels and inversely associated with adiponectin. At baseline, high CEC was associated with decreased flow-mediated dilation (FMD) and carotid artery distensibility, as well as an increased Young's modulus of elasticity, indicating adverse changes in arterial structure, and function. The association reversed with follow-up FMD data, indicating the interaction of preclinical parameters over time. A higher CEC was directly associated with a lower risk of subclinical atherosclerosis at follow-up. In young and healthy subjects, CEC was associated with important lipid risk parameters at baseline, as in older patients and CAD patients, but inversely with early risk markers for subclinical atherosclerosis.
Published: 2020
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19. Whole blood microRNA levels associate with glycemic status and correlate with target mRNAs in pathways important to type 2 diabetes.

Author: Mononen N, Lyytikäinen LP, Seppälä I, Mishra PP, Juonala M, Waldenberger M, Klopp N, Illig T, Leiviskä J, Loo BM, Laaksonen R, Oksala N, Kähönen M, Hutri-Kähönen N, Raitakari O, Lehtimäki T, and Raitoharju E
Subjects: Humans, Blood Glucose metabolism, Diabetes Mellitus, Type 2 blood, MicroRNAs blood, RNA, Messenger blood
Abstract: We analyzed the associations between whole blood microRNA profiles and the indices of glucose metabolism and impaired fasting glucose and examined whether the discovered microRNAs correlate with the expression of their mRNA targets. MicroRNA and gene expression profiling were performed for the Young Finns Study participants (n = 871). Glucose, insulin, and glycated hemoglobin (HbA1c) levels were measured, the insulin resistance index (HOMA2-IR) was calculated, and the glycemic status (normoglycemic [n = 534]/impaired fasting glucose [IFG] [n = 252]/type 2 diabetes [T2D] [n = 24]) determined. Levels of hsa-miR-144-5p, -122-5p, -148a-3p, -589-5p, and hsa-let-7a-5p associated with glycemic status. hsa-miR-144-5p and -148a-3p associated with glucose levels, while hsa-miR-144-5p, -122-5p, -184, and -339-3p associated with insulin levels and HOMA2-IR, and hsa-miR-148a-3p, -15b-3p, -93-3p, -146b-5p, -221-3p, -18a-3p, -642a-5p, and -181-2-3p associated with HbA1c levels. The targets of hsa-miR-146b-5p that correlated with its levels were enriched in inflammatory pathways, and the targets of hsa-miR-221-3p were enriched in insulin signaling and T2D pathways. These pathways showed indications of co-regulation by HbA1c-associated miRNAs. There were significant differences in the microRNA profiles associated with glucose, insulin, or HOMA-IR compared to those associated with HbA1c. The HbA1c-associated miRNAs also correlated with the expression of target mRNAs in pathways important to the development of T2D.
Published: 2019
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20. The effect of apolipoprotein E polymorphism on serum metabolome - a population-based 10-year follow-up study.

Author: Karjalainen JP, Mononen N, Hutri-Kähönen N, Lehtimäki M, Juonala M, Ala-Korpela M, Kähönen M, Raitakari O, and Lehtimäki T
Subjects: Adult, Alleles, Cross-Sectional Studies, Disease Susceptibility, Female, Gene Frequency, Genotype, Humans, Longitudinal Studies, Male, Young Adult, Apolipoproteins E genetics, Biomarkers blood, Metabolome, Metabolomics methods, Polymorphism, Genetic
Abstract: Apolipoprotein E (apoE) is the key regulator of plasma lipids, mediating altered functionalities in lipoprotein metabolism - affecting the risk of coronary artery (CAD) and Alzheimer's diseases, as well as longevity. Searching pathways influenced by apoE prior to adverse manifestations, we utilized a metabolome dataset of 228 nuclear-magnetic-resonance-measured serum parameters with a 10-year follow-up from the population-based Young Finns Study cohort of 2,234 apoE-genotyped (rs7412, rs429358) adults, aged 24-39 at baseline. At the end of our follow-up, by limiting FDR-corrected p < 0.05, regression analyses revealed 180/228 apoE-polymorphism-related associations with the studied metabolites, in all subjects - without indications of apoE x sex interactions. Across all measured apoE- and apoB-containing lipoproteins, ε4 allele had consistently atherogenic and ε2 protective effect on particle concentrations of free/esterified cholesterol, triglycerides, phospholipids and total lipids. As novel findings, ε4 associated with glycoprotein acetyls, LDL-diameter and isoleucine - all reported biomarkers of CAD-risk, inflammation, diabetes and total mortality. ApoE-subgroup differences persisted through our 10-year follow-up, although some variation of individual metabolite levels was noticed. In conclusion, apoE polymorphism associate with a complex metabolic change, including aberrations in multiple novel biomarkers related to elevated cardiometabolic and all-cause mortality risk, extending our understanding about the role of apoE in health and disease.
Published: 2019
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21. Circulating metabolic biomarkers of renal function in diabetic and non-diabetic populations.

Author: Barrios C, Zierer J, Würtz P, Haller T, Metspalu A, Gieger C, Thorand B, Meisinger C, Waldenberger M, Raitakari O, Lehtimäki T, Otero S, Rodríguez E, Pedro-Botet J, Kähönen M, Ala-Korpela M, Kastenmüller G, Spector TD, Pascual J, and Menni C
Subjects: Aged, Aged, 80 and over, Case-Control Studies, Cohort Studies, Cross-Sectional Studies, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 diagnosis, Diabetes Mellitus, Type 2 physiopathology, Diabetic Nephropathies blood, Diabetic Nephropathies diagnosis, Female, Glomerular Filtration Rate, Humans, Male, Middle Aged, Renal Insufficiency, Chronic blood, Renal Insufficiency, Chronic complications, Renal Insufficiency, Chronic diagnosis, Biomarkers blood, Diabetes Mellitus, Type 2 blood, Kidney physiology, Kidney Function Tests methods
Abstract: Using targeted NMR spectroscopy of 227 fasting serum metabolic traits, we searched for novel metabolic signatures of renal function in 926 type 2 diabetics (T2D) and 4838 non-diabetic individuals from four independent cohorts. We furthermore investigated longitudinal changes of metabolic measures and renal function and associations with other T2D microvascular complications. 142 traits correlated with glomerular filtration rate (eGFR) after adjusting for confounders and multiple testing: 59 in diabetics, 109 in non-diabetics with 26 overlapping. The amino acids glycine and phenylalanine and the energy metabolites citrate and glycerol were negatively associated with eGFR in all the cohorts, while alanine, valine and pyruvate depicted opposite association in diabetics (positive) and non-diabetics (negative). Moreover, in all cohorts, the triglyceride content of different lipoprotein subclasses showed a negative association with eGFR, while cholesterol, cholesterol esters (CE), and phospholipids in HDL were associated with better renal function. In contrast, phospholipids and CEs in LDL showed positive associations with eGFR only in T2D, while phospholipid content in HDL was positively associated with eGFR both cross-sectionally and longitudinally only in non-diabetics. In conclusion, we provide a wide list of kidney function-associated metabolic traits and identified novel metabolic differences between diabetic and non-diabetic kidney disease.
Published: 2018
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22. Fatty liver is associated with blood pathways of inflammatory response, immune system activation and prothrombotic state in Young Finns Study.

Author: Taipale T, Seppälä I, Raitoharju E, Mononen N, Lyytikäinen LP, Illig T, Waldenberger M, Juonala M, Hutri-Kähönen N, Oksala N, Kähönen M, Raitakari O, and Lehtimäki T
Subjects: Adult, Biomarkers blood, Biomarkers metabolism, CD40 Antigens genetics, CD40 Antigens metabolism, CD40 Ligand genetics, CD40 Ligand metabolism, Case-Control Studies, Extracellular Matrix metabolism, Fatty Liver genetics, Fatty Liver pathology, Female, Finland, Gene Expression Regulation, Humans, Integrin alpha4beta1 genetics, Integrin alpha4beta1 metabolism, Leukocytes cytology, Leukocytes physiology, Liver diagnostic imaging, Liver metabolism, Male, Middle Aged, Netrin-1 genetics, Netrin-1 metabolism, Risk Factors, Fatty Liver blood, Immune System metabolism, Signal Transduction genetics
Abstract: Fatty liver (FL) disease is the most common type of chronic liver disease. We hypothesized that liver's response to the process where large droplets of triglyceride fat accumulate in liver cells is reflected also in gene pathway expression in blood. Peripheral blood genome wide gene expression analysis and ultrasonic imaging of liver were performed for 1,650 participants (316 individuals with FL and 1,334 controls) of the Young Finns Study. Gene set enrichment analysis (GSEA) was performed for the expression data. Fourteen gene sets were upregulated (false discovery rate, FDR < 0.05) in subjects with FL. These pathways related to extracellular matrix (ECM) turnover, immune response regulation, prothrombotic state and neural tissues. After adjustment for known risk factors and biomarkers of FL, we found i) integrin A4B1 signaling, ii) leukocyte transendothelial migration, iii) CD40/CD40L and iv) netrin-1 signaling pathways to be upregulated in individuals with FL (nominal p < 0.05). From these all but not ii) remained significantly upregulated when analyzing only subjects without history of heavy alcohol use. In conclusion, FL was associated with blood gene sets of ECM turnover, inflammatory response, immune system activation and prothrombotic state. These may form a systemic link between FL and the development of cardiovascular diseases.
Published: 2018
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23. Association of circulating metabolites with healthy diet and risk of cardiovascular disease: analysis of two cohort studies.

Author: Akbaraly T, Würtz P, Singh-Manoux A, Shipley MJ, Haapakoski R, Lehto M, Desrumaux C, Kähönen M, Lehtimäki T, Mikkilä V, Hingorani A, Humphries SE, Kangas AJ, Soininen P, Raitakari O, Ala-Korpela M, and Kivimäki M
Subjects: Adult, Cohort Studies, Female, Humans, Magnetic Resonance Spectroscopy, Male, Metabolomics, Middle Aged, Risk Assessment, Biological Factors blood, Cardiovascular Diseases diagnosis, Cardiovascular Diseases physiopathology, Diet, Healthy, Metabolome
Abstract: Diet may modify metabolomic profiles towards higher or lower cardiovascular disease (CVD) risk. We aimed to identify metabolite profiles associated with high adherence to dietary recommendations - the Alternative Healthy Eating Index (AHEI) - and the extent to which metabolites associated with AHEI also predict incident CVD. Relations between AHEI score and 80 circulating lipids and metabolites, quantified by nuclear magnetic resonance metabolomics, were examined using linear regression models in the Whitehall II study (n = 4824, 55.9 ± 6.1 years, 28.0% women) and were replicated in the Cardiovascular Risk in Young Finns Study (n = 1716, 37.7 ± 5.0 years, 56.3% women). We used Cox models to study associations between metabolites and incident CVD over the 15.8-year follow-up in the Whitehall II study. After adjustment for confounders, higher AHEI score (indicating healthier diet) was associated with higher degree of unsaturation of fatty acids (FA) and higher ratios of polyunsaturated FA, omega-3 and docosahexaenoic acid relative to total FA in both Whitehall II and Young Finns studies. A concordance of associations of metabolites with higher AHEI score and lower CVD risk was observed in Whitehall II. Adherence to healthy diet seems to be associated with specific FA that reduce risk of CVD.
Published: 2018
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24. Effects of childhood and adolescence physical activity patterns on psychosis risk-a general population cohort study.

Author: Sormunen E, Saarinen MM, Salokangas RKR, Telama R, Hutri-Kähönen N, Tammelin T, Viikari J, Raitakari O, and Hietala J
Abstract: Schizophrenia spectrum disorders are associated with high morbidity and mortality in somatic diseases. The risk factors of this excess mortality include, e.g., obesity, dietary factors, and physical inactivity, especially after the onset of psychosis, but there are limited early developmental data on these factors in individuals who later develop psychosis. A population-based cohort study "Cardiovascular Risk of Young Finns" started in 1980 with 3596 children and adolescents from six different age groups (3, 6, 9, 12, 15, and 18 years). Cardiovascular health parameters, including questionnaire of physical activity before first hospitalization (≤18 years), were studied in 1980, 1983, and 1986. All psychiatric diagnoses of the participants were derived from the Finnish Hospital Discharge Register up to the year 2012. We identified diagnostic groups of non-affective psychosis ( n = 68, including a schizophrenia subgroup, n = 41), personality disorders ( n = 43), affective disorders ( n = 111), and substance-related disorders ( n = 49), based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Groups were compared with controls with no psychiatric diagnoses ( n = 3325). Sex, age, body mass index, birth weight, non-preterm birth, and mother's mental disorders were included in the statistical model. Low physical activity in childhood and adolescence (9-18 years) independently predicted later development of non-affective psychosis. Lower physical activity index (relative risk 1.26 [1.1-1.5]), lower level of common activity during leisure time (relative risk 1.71 [1.2-2.5]), and non-participation in sports competitions (relative risk 2.58 [1.3-5.3]) were associated with a higher risk for later non-affective psychosis (expressed as increase in relative risk per physical activity unit). The findings were even stronger for schizophrenia, but no such link was observed for other diagnoses. The cause of low physical activity in premorbid/prodromal phase is likely to be multifactorial, including deviant motor and cognitive development. The results provide a rationale for including exercise and physical activity interventions as a part of psychosis prevention programs.
Published: 2017
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25. Blood hsa-miR-122-5p and hsa-miR-885-5p levels associate with fatty liver and related lipoprotein metabolism-The Young Finns Study.

Author: Raitoharju E, Seppälä I, Lyytikäinen LP, Viikari J, Ala-Korpela M, Soininen P, Kangas AJ, Waldenberger M, Klopp N, Illig T, Leiviskä J, Loo BM, Oksala N, Kähönen M, Hutri-Kähönen N, Laaksonen R, Raitakari O, and Lehtimäki T
Subjects: Adolescent, Adult, Child, Child, Preschool, Fatty Liver diagnostic imaging, Fatty Liver epidemiology, Female, Finland epidemiology, Follow-Up Studies, Genome-Wide Association Study, Humans, Male, Middle Aged, Ultrasonography, Fatty Liver blood, Lipoproteins blood, MicroRNAs blood
Abstract: MicroRNAs are involved in disease development and may be utilized as biomarkers. We investigated the association of blood miRNA levels and a) fatty liver (FL), b) lipoprotein and lipid pathways involved in liver lipid accumulation and c) levels of predicted mRNA targets in general population based cohort. Blood microRNA profiling (TaqMan OpenArray), genome-wide gene expression arrays and nuclear magnetic resonance metabolomics were performed for Young Finns Study participants aged 34-49 years (n = 871). Liver fat status was assessed ultrasonographically. Levels of hsa-miR-122-5p and -885-5p were up-regulated in individuals with FL (fold change (FC) = 1.55, p = 1.36 * 10 -14 and FC = 1.25, p = 4.86 * 10 -4 , respectively). In regression model adjusted with age, sex and BMI, hsa-miR-122-5p and -885-5p predicted FL (OR = 2.07, p = 1.29 * 10 -8 and OR = 1.41, p = 0.002, respectively). Together hsa-miR-122-5p and -885-5p slightly improved the detection of FL beyond established risk factors. These miRNAs may be associated with FL formation through the regulation of lipoprotein metabolism as hsa-miR-122-5p levels associated with small VLDL, IDL, and large LDL lipoprotein subclass components, while hsa-miR-885-5p levels associated inversely with XL HDL cholesterol levels. Hsa-miR-885-5p levels correlated inversely with oxysterol-binding protein 2 (OSBPL2) expression (r = -0.143, p = 1.00 * 10 -4 ) and suppressing the expression of this lipid receptor and sterol transporter could link hsa-miR-885-5p with HDL cholesterol levels., Competing Interests: MAK, PS, and AJK are shareholders in Brainshake Ltd., a company offering NMR-based metabolite profiling.
Published: 2016
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26. Genome-wide association study identifies 74 loci associated with educational attainment.

Author: Okbay A, Beauchamp JP, Fontana MA, Lee JJ, Pers TH, Rietveld CA, Turley P, Chen GB, Emilsson V, Meddens SF, Oskarsson S, Pickrell JK, Thom K, Timshel P, de Vlaming R, Abdellaoui A, Ahluwalia TS, Bacelis J, Baumbach C, Bjornsdottir G, Brandsma JH, Pina Concas M, Derringer J, Furlotte NA, Galesloot TE, Girotto G, Gupta R, Hall LM, Harris SE, Hofer E, Horikoshi M, Huffman JE, Kaasik K, Kalafati IP, Karlsson R, Kong A, Lahti J, van der Lee SJ, deLeeuw C, Lind PA, Lindgren KO, Liu T, Mangino M, Marten J, Mihailov E, Miller MB, van der Most PJ, Oldmeadow C, Payton A, Pervjakova N, Peyrot WJ, Qian Y, Raitakari O, Rueedi R, Salvi E, Schmidt B, Schraut KE, Shi J, Smith AV, Poot RA, St Pourcain B, Teumer A, Thorleifsson G, Verweij N, Vuckovic D, Wellmann J, Westra HJ, Yang J, Zhao W, Zhu Z, Alizadeh BZ, Amin N, Bakshi A, Baumeister SE, Biino G, Bønnelykke K, Boyle PA, Campbell H, Cappuccio FP, Davies G, De Neve JE, Deloukas P, Demuth I, Ding J, Eibich P, Eisele L, Eklund N, Evans DM, Faul JD, Feitosa MF, Forstner AJ, Gandin I, Gunnarsson B, Halldórsson BV, Harris TB, Heath AC, Hocking LJ, Holliday EG, Homuth G, Horan MA, Hottenga JJ, de Jager PL, Joshi PK, Jugessur A, Kaakinen MA, Kähönen M, Kanoni S, Keltigangas-Järvinen L, Kiemeney LA, Kolcic I, Koskinen S, Kraja AT, Kroh M, Kutalik Z, Latvala A, Launer LJ, Lebreton MP, Levinson DF, Lichtenstein P, Lichtner P, Liewald DC, Loukola A, Madden PA, Mägi R, Mäki-Opas T, Marioni RE, Marques-Vidal P, Meddens GA, McMahon G, Meisinger C, Meitinger T, Milaneschi Y, Milani L, Montgomery GW, Myhre R, Nelson CP, Nyholt DR, Ollier WE, Palotie A, Paternoster L, Pedersen NL, Petrovic KE, Porteous DJ, Räikkönen K, Ring SM, Robino A, Rostapshova O, Rudan I, Rustichini A, Salomaa V, Sanders AR, Sarin AP, Schmidt H, Scott RJ, Smith BH, Smith JA, Staessen JA, Steinhagen-Thiessen E, Strauch K, Terracciano A, Tobin MD, Ulivi S, Vaccargiu S, Quaye L, van Rooij FJ, Venturini C, Vinkhuyzen AA, Völker U, Völzke H, Vonk JM, Vozzi D, Waage J, Ware EB, Willemsen G, Attia JR, Bennett DA, Berger K, Bertram L, Bisgaard H, Boomsma DI, Borecki IB, Bültmann U, Chabris CF, Cucca F, Cusi D, Deary IJ, Dedoussis GV, van Duijn CM, Eriksson JG, Franke B, Franke L, Gasparini P, Gejman PV, Gieger C, Grabe HJ, Gratten J, Groenen PJ, Gudnason V, van der Harst P, Hayward C, Hinds DA, Hoffmann W, Hyppönen E, Iacono WG, Jacobsson B, Järvelin MR, Jöckel KH, Kaprio J, Kardia SL, Lehtimäki T, Lehrer SF, Magnusson PK, Martin NG, McGue M, Metspalu A, Pendleton N, Penninx BW, Perola M, Pirastu N, Pirastu M, Polasek O, Posthuma D, Power C, Province MA, Samani NJ, Schlessinger D, Schmidt R, Sørensen TI, Spector TD, Stefansson K, Thorsteinsdottir U, Thurik AR, Timpson NJ, Tiemeier H, Tung JY, Uitterlinden AG, Vitart V, Vollenweider P, Weir DR, Wilson JF, Wright AF, Conley DC, Krueger RF, Davey Smith G, Hofman A, Laibson DI, Medland SE, Meyer MN, Yang J, Johannesson M, Visscher PM, Esko T, Koellinger PD, Cesarini D, and Benjamin DJ
Subjects: Alzheimer Disease genetics, Bipolar Disorder genetics, Cognition, Computational Biology, Gene-Environment Interaction, Humans, Molecular Sequence Annotation, Schizophrenia genetics, United Kingdom, Brain metabolism, Educational Status, Fetus metabolism, Gene Expression Regulation genetics, Genome-Wide Association Study, Polymorphism, Single Nucleotide genetics
Abstract: Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
Published: 2016
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27. Directional dominance on stature and cognition in diverse human populations.

Author: Joshi PK, Esko T, Mattsson H, Eklund N, Gandin I, Nutile T, Jackson AU, Schurmann C, Smith AV, Zhang W, Okada Y, Stančáková A, Faul JD, Zhao W, Bartz TM, Concas MP, Franceschini N, Enroth S, Vitart V, Trompet S, Guo X, Chasman DI, O'Connel JR, Corre T, Nongmaithem SS, Chen Y, Mangino M, Ruggiero D, Traglia M, Farmaki AE, Kacprowski T, Bjonnes A, van der Spek A, Wu Y, Giri AK, Yanek LR, Wang L, Hofer E, Rietveld CA, McLeod O, Cornelis MC, Pattaro C, Verweij N, Baumbach C, Abdellaoui A, Warren HR, Vuckovic D, Mei H, Bouchard C, Perry JRB, Cappellani S, Mirza SS, Benton MC, Broeckel U, Medland SE, Lind PA, Malerba G, Drong A, Yengo L, Bielak LF, Zhi D, van der Most PJ, Shriner D, Mägi R, Hemani G, Karaderi T, Wang Z, Liu T, Demuth I, Zhao JH, Meng W, Lataniotis L, van der Laan SW, Bradfield JP, Wood AR, Bonnefond A, Ahluwalia TS, Hall LM, Salvi E, Yazar S, Carstensen L, de Haan HG, Abney M, Afzal U, Allison MA, Amin N, Asselbergs FW, Bakker SJL, Barr RG, Baumeister SE, Benjamin DJ, Bergmann S, Boerwinkle E, Bottinger EP, Campbell A, Chakravarti A, Chan Y, Chanock SJ, Chen C, Chen YI, Collins FS, Connell J, Correa A, Cupples LA, Smith GD, Davies G, Dörr M, Ehret G, Ellis SB, Feenstra B, Feitosa MF, Ford I, Fox CS, Frayling TM, Friedrich N, Geller F, Scotland G, Gillham-Nasenya I, Gottesman O, Graff M, Grodstein F, Gu C, Haley C, Hammond CJ, Harris SE, Harris TB, Hastie ND, Heard-Costa NL, Heikkilä K, Hocking LJ, Homuth G, Hottenga JJ, Huang J, Huffman JE, Hysi PG, Ikram MA, Ingelsson E, Joensuu A, Johansson Å, Jousilahti P, Jukema JW, Kähönen M, Kamatani Y, Kanoni S, Kerr SM, Khan NM, Koellinger P, Koistinen HA, Kooner MK, Kubo M, Kuusisto J, Lahti J, Launer LJ, Lea RA, Lehne B, Lehtimäki T, Liewald DCM, Lind L, Loh M, Lokki ML, London SJ, Loomis SJ, Loukola A, Lu Y, Lumley T, Lundqvist A, Männistö S, Marques-Vidal P, Masciullo C, Matchan A, Mathias RA, Matsuda K, Meigs JB, Meisinger C, Meitinger T, Menni C, Mentch FD, Mihailov E, Milani L, Montasser ME, Montgomery GW, Morrison A, Myers RH, Nadukuru R, Navarro P, Nelis M, Nieminen MS, Nolte IM, O'Connor GT, Ogunniyi A, Padmanabhan S, Palmas WR, Pankow JS, Patarcic I, Pavani F, Peyser PA, Pietilainen K, Poulter N, Prokopenko I, Ralhan S, Redmond P, Rich SS, Rissanen H, Robino A, Rose LM, Rose R, Sala C, Salako B, Salomaa V, Sarin AP, Saxena R, Schmidt H, Scott LJ, Scott WR, Sennblad B, Seshadri S, Sever P, Shrestha S, Smith BH, Smith JA, Soranzo N, Sotoodehnia N, Southam L, Stanton AV, Stathopoulou MG, Strauch K, Strawbridge RJ, Suderman MJ, Tandon N, Tang ST, Taylor KD, Tayo BO, Töglhofer AM, Tomaszewski M, Tšernikova N, Tuomilehto J, Uitterlinden AG, Vaidya D, van Hylckama Vlieg A, van Setten J, Vasankari T, Vedantam S, Vlachopoulou E, Vozzi D, Vuoksimaa E, Waldenberger M, Ware EB, Wentworth-Shields W, Whitfield JB, Wild S, Willemsen G, Yajnik CS, Yao J, Zaza G, Zhu X, Project TBJ, Salem RM, Melbye M, Bisgaard H, Samani NJ, Cusi D, Mackey DA, Cooper RS, Froguel P, Pasterkamp G, Grant SFA, Hakonarson H, Ferrucci L, Scott RA, Morris AD, Palmer CNA, Dedoussis G, Deloukas P, Bertram L, Lindenberger U, Berndt SI, Lindgren CM, Timpson NJ, Tönjes A, Munroe PB, Sørensen TIA, Rotimi CN, Arnett DK, Oldehinkel AJ, Kardia SLR, Balkau B, Gambaro G, Morris AP, Eriksson JG, Wright MJ, Martin NG, Hunt SC, Starr JM, Deary IJ, Griffiths LR, Tiemeier H, Pirastu N, Kaprio J, Wareham NJ, Pérusse L, Wilson JG, Girotto G, Caulfield MJ, Raitakari O, Boomsma DI, Gieger C, van der Harst P, Hicks AA, Kraft P, Sinisalo J, Knekt P, Johannesson M, Magnusson PKE, Hamsten A, Schmidt R, Borecki IB, Vartiainen E, Becker DM, Bharadwaj D, Mohlke KL, Boehnke M, van Duijn CM, Sanghera DK, Teumer A, Zeggini E, Metspalu A, Gasparini P, Ulivi S, Ober C, Toniolo D, Rudan I, Porteous DJ, Ciullo M, Spector TD, Hayward C, Dupuis J, Loos RJF, Wright AF, Chandak GR, Vollenweider P, Shuldiner A, Ridker PM, Rotter JI, Sattar N, Gyllensten U, North KE, Pirastu M, Psaty BM, Weir DR, Laakso M, Gudnason V, Takahashi A, Chambers JC, Kooner JS, Strachan DP, Campbell H, Hirschhorn JN, Perola M, Polašek O, and Wilson JF
Subjects: Biological Evolution, Blood Pressure genetics, Cholesterol, LDL genetics, Cohort Studies, Educational Status, Female, Forced Expiratory Volume genetics, Genome, Human genetics, Humans, Lung Volume Measurements, Male, Phenotype, Body Height genetics, Cognition, Homozygote
Abstract: Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
Published: 2015
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28. Vigorous physical activity and carotid distensibility in young and mid-aged adults.

Author: Huynh QL, Blizzard CL, Raitakari O, Sharman JE, Magnussen CG, Dwyer T, Juonala M, Kähönen M, and Venn AJ
Subjects: Adult, Australia, Blood Pressure physiology, Elasticity physiology, Female, Finland, Heart Rate physiology, Humans, Male, Middle Aged, Carotid Arteries physiology, Exercise physiology, Motor Activity physiology, Physical Fitness physiology
Abstract: Although physical activity (PA) improves arterial distensibility, it is unclear which type of activity is most beneficial. We aimed to examine the association of different types of PA with carotid distensibility (CD) and the mechanisms involved. Data included 4503 Australians and Finns aged 26-45 years. Physical activity was measured by pedometers and was self-reported. CD was measured using ultrasound. Other measurements included resting heart rate (RHR), cardiorespiratory fitness (CRF), blood pressure, biomarkers and anthropometry. Steps/day were correlated with RHR (Australian men r = -0.10, women r = - 0.14; Finnish men r = -0.15, women r = -0.11; P<0.01), CRF and biochemical markers, but not with CD. Self-reported vigorous leisure-time activity was more strongly correlated with RHR (Australian men r = -0.23, women r = -0.19; Finnish men r = -0.20, women r = -0.13; P < 0.001) and CRF, and was correlated with CD (Australian men r = 0.07; Finnish men r = 0.07, women r = 0.08; P < 0.05). This relationship of vigorous leisure-time activity with CD was mediated by RHR independently of potential confounders. In summary, vigorous leisure-time PA but not total or less intensive PA was associated with arterial distensibility in young to mid-aged adults. Promotion of vigorous PA is therefore recommended among this population. RHR was a key intermediary factor explaining the relationship between vigorous PA and arterial distensibility.
Published: 2015
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29. Seventy-five genetic loci influencing the human red blood cell.

Author: van der Harst P, Zhang W, Mateo Leach I, Rendon A, Verweij N, Sehmi J, Paul DS, Elling U, Allayee H, Li X, Radhakrishnan A, Tan ST, Voss K, Weichenberger CX, Albers CA, Al-Hussani A, Asselbergs FW, Ciullo M, Danjou F, Dina C, Esko T, Evans DM, Franke L, Gögele M, Hartiala J, Hersch M, Holm H, Hottenga JJ, Kanoni S, Kleber ME, Lagou V, Langenberg C, Lopez LM, Lyytikäinen LP, Melander O, Murgia F, Nolte IM, O'Reilly PF, Padmanabhan S, Parsa A, Pirastu N, Porcu E, Portas L, Prokopenko I, Ried JS, Shin SY, Tang CS, Teumer A, Traglia M, Ulivi S, Westra HJ, Yang J, Zhao JH, Anni F, Abdellaoui A, Attwood A, Balkau B, Bandinelli S, Bastardot F, Benyamin B, Boehm BO, Cookson WO, Das D, de Bakker PI, de Boer RA, de Geus EJ, de Moor MH, Dimitriou M, Domingues FS, Döring A, Engström G, Eyjolfsson GI, Ferrucci L, Fischer K, Galanello R, Garner SF, Genser B, Gibson QD, Girotto G, Gudbjartsson DF, Harris SE, Hartikainen AL, Hastie CE, Hedblad B, Illig T, Jolley J, Kähönen M, Kema IP, Kemp JP, Liang L, Lloyd-Jones H, Loos RJ, Meacham S, Medland SE, Meisinger C, Memari Y, Mihailov E, Miller K, Moffatt MF, Nauck M, Novatchkova M, Nutile T, Olafsson I, Onundarson PT, Parracciani D, Penninx BW, Perseu L, Piga A, Pistis G, Pouta A, Puc U, Raitakari O, Ring SM, Robino A, Ruggiero D, Ruokonen A, Saint-Pierre A, Sala C, Salumets A, Sambrook J, Schepers H, Schmidt CO, Silljé HH, Sladek R, Smit JH, Starr JM, Stephens J, Sulem P, Tanaka T, Thorsteinsdottir U, Tragante V, van Gilst WH, van Pelt LJ, van Veldhuisen DJ, Völker U, Whitfield JB, Willemsen G, Winkelmann BR, Wirnsberger G, Algra A, Cucca F, d'Adamo AP, Danesh J, Deary IJ, Dominiczak AF, Elliott P, Fortina P, Froguel P, Gasparini P, Greinacher A, Hazen SL, Jarvelin MR, Khaw KT, Lehtimäki T, Maerz W, Martin NG, Metspalu A, Mitchell BD, Montgomery GW, Moore C, Navis G, Pirastu M, Pramstaller PP, Ramirez-Solis R, Schadt E, Scott J, Shuldiner AR, Smith GD, Smith JG, Snieder H, Sorice R, Spector TD, Stefansson K, Stumvoll M, Tang WH, Toniolo D, Tönjes A, Visscher PM, Vollenweider P, Wareham NJ, Wolffenbuttel BH, Boomsma DI, Beckmann JS, Dedoussis GV, Deloukas P, Ferreira MA, Sanna S, Uda M, Hicks AA, Penninger JM, Gieger C, Kooner JS, Ouwehand WH, Soranzo N, and Chambers JC
Subjects: Animals, Cell Cycle genetics, Cytokines metabolism, Drosophila melanogaster genetics, Erythrocytes cytology, Female, Gene Expression Regulation genetics, Hematopoiesis genetics, Hemoglobins genetics, Humans, Male, Mice, Organ Specificity, Polymorphism, Single Nucleotide genetics, RNA Interference, Signal Transduction genetics, Erythrocytes metabolism, Genetic Loci, Genome-Wide Association Study, Phenotype
Abstract: Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
Published: 2012
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30. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Author: Ehret GB, Munroe PB, Rice KM, Bochud M, Johnson AD, Chasman DI, Smith AV, Tobin MD, Verwoert GC, Hwang SJ, Pihur V, Vollenweider P, O'Reilly PF, Amin N, Bragg-Gresham JL, Teumer A, Glazer NL, Launer L, Zhao JH, Aulchenko Y, Heath S, Sõber S, Parsa A, Luan J, Arora P, Dehghan A, Zhang F, Lucas G, Hicks AA, Jackson AU, Peden JF, Tanaka T, Wild SH, Rudan I, Igl W, Milaneschi Y, Parker AN, Fava C, Chambers JC, Fox ER, Kumari M, Go MJ, van der Harst P, Kao WH, Sjögren M, Vinay DG, Alexander M, Tabara Y, Shaw-Hawkins S, Whincup PH, Liu Y, Shi G, Kuusisto J, Tayo B, Seielstad M, Sim X, Nguyen KD, Lehtimäki T, Matullo G, Wu Y, Gaunt TR, Onland-Moret NC, Cooper MN, Platou CG, Org E, Hardy R, Dahgam S, Palmen J, Vitart V, Braund PS, Kuznetsova T, Uiterwaal CS, Adeyemo A, Palmas W, Campbell H, Ludwig B, Tomaszewski M, Tzoulaki I, Palmer ND, Aspelund T, Garcia M, Chang YP, O'Connell JR, Steinle NI, Grobbee DE, Arking DE, Kardia SL, Morrison AC, Hernandez D, Najjar S, McArdle WL, Hadley D, Brown MJ, Connell JM, Hingorani AD, Day IN, Lawlor DA, Beilby JP, Lawrence RW, Clarke R, Hopewell JC, Ongen H, Dreisbach AW, Li Y, Young JH, Bis JC, Kähönen M, Viikari J, Adair LS, Lee NR, Chen MH, Olden M, Pattaro C, Bolton JA, Köttgen A, Bergmann S, Mooser V, Chaturvedi N, Frayling TM, Islam M, Jafar TH, Erdmann J, Kulkarni SR, Bornstein SR, Grässler J, Groop L, Voight BF, Kettunen J, Howard P, Taylor A, Guarrera S, Ricceri F, Emilsson V, Plump A, Barroso I, Khaw KT, Weder AB, Hunt SC, Sun YV, Bergman RN, Collins FS, Bonnycastle LL, Scott LJ, Stringham HM, Peltonen L, Perola M, Vartiainen E, Brand SM, Staessen JA, Wang TJ, Burton PR, Soler Artigas M, Dong Y, Snieder H, Wang X, Zhu H, Lohman KK, Rudock ME, Heckbert SR, Smith NL, Wiggins KL, Doumatey A, Shriner D, Veldre G, Viigimaa M, Kinra S, Prabhakaran D, Tripathy V, Langefeld CD, Rosengren A, Thelle DS, Corsi AM, Singleton A, Forrester T, Hilton G, McKenzie CA, Salako T, Iwai N, Kita Y, Ogihara T, Ohkubo T, Okamura T, Ueshima H, Umemura S, Eyheramendy S, Meitinger T, Wichmann HE, Cho YS, Kim HL, Lee JY, Scott J, Sehmi JS, Zhang W, Hedblad B, Nilsson P, Smith GD, Wong A, Narisu N, Stančáková A, Raffel LJ, Yao J, Kathiresan S, O'Donnell CJ, Schwartz SM, Ikram MA, Longstreth WT Jr, Mosley TH, Seshadri S, Shrine NR, Wain LV, Morken MA, Swift AJ, Laitinen J, Prokopenko I, Zitting P, Cooper JA, Humphries SE, Danesh J, Rasheed A, Goel A, Hamsten A, Watkins H, Bakker SJ, van Gilst WH, Janipalli CS, Mani KR, Yajnik CS, Hofman A, Mattace-Raso FU, Oostra BA, Demirkan A, Isaacs A, Rivadeneira F, Lakatta EG, Orru M, Scuteri A, Ala-Korpela M, Kangas AJ, Lyytikäinen LP, Soininen P, Tukiainen T, Würtz P, Ong RT, Dörr M, Kroemer HK, Völker U, Völzke H, Galan P, Hercberg S, Lathrop M, Zelenika D, Deloukas P, Mangino M, Spector TD, Zhai G, Meschia JF, Nalls MA, Sharma P, Terzic J, Kumar MV, Denniff M, Zukowska-Szczechowska E, Wagenknecht LE, Fowkes FG, Charchar FJ, Schwarz PE, Hayward C, Guo X, Rotimi C, Bots ML, Brand E, Samani NJ, Polasek O, Talmud PJ, Nyberg F, Kuh D, Laan M, Hveem K, Palmer LJ, van der Schouw YT, Casas JP, Mohlke KL, Vineis P, Raitakari O, Ganesh SK, Wong TY, Tai ES, Cooper RS, Laakso M, Rao DC, Harris TB, Morris RW, Dominiczak AF, Kivimaki M, Marmot MG, Miki T, Saleheen D, Chandak GR, Coresh J, Navis G, Salomaa V, Han BG, Zhu X, Kooner JS, Melander O, Ridker PM, Bandinelli S, Gyllensten UB, Wright AF, Wilson JF, Ferrucci L, Farrall M, Tuomilehto J, Pramstaller PP, Elosua R, Soranzo N, Sijbrands EJ, Altshuler D, Loos RJ, Shuldiner AR, Gieger C, Meneton P, Uitterlinden AG, Wareham NJ, Gudnason V, Rotter JI, Rettig R, Uda M, Strachan DP, Witteman JC, Hartikainen AL, Beckmann JS, Boerwinkle E, Vasan RS, Boehnke M, Larson MG, Järvelin MR, Psaty BM, Abecasis GR, Chakravarti A, Elliott P, van Duijn CM, Newton-Cheh C, Levy D, Caulfield MJ, and Johnson T
Subjects: Africa ethnology, Asia ethnology, Blood Pressure physiology, Coronary Artery Disease genetics, Europe ethnology, Genome-Wide Association Study, Humans, Hypertension genetics, Kidney Diseases genetics, Stroke genetics, Blood Pressure genetics, Cardiovascular Diseases genetics, Genetic Predisposition to Disease genetics, Polymorphism, Single Nucleotide genetics
Abstract: Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.
Published: 2011
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31. Hundreds of variants clustered in genomic loci and biological pathways affect human height.

Author: Lango Allen H, Estrada K, Lettre G, Berndt SI, Weedon MN, Rivadeneira F, Willer CJ, Jackson AU, Vedantam S, Raychaudhuri S, Ferreira T, Wood AR, Weyant RJ, Segrè AV, Speliotes EK, Wheeler E, Soranzo N, Park JH, Yang J, Gudbjartsson D, Heard-Costa NL, Randall JC, Qi L, Vernon Smith A, Mägi R, Pastinen T, Liang L, Heid IM, Luan J, Thorleifsson G, Winkler TW, Goddard ME, Sin Lo K, Palmer C, Workalemahu T, Aulchenko YS, Johansson A, Zillikens MC, Feitosa MF, Esko T, Johnson T, Ketkar S, Kraft P, Mangino M, Prokopenko I, Absher D, Albrecht E, Ernst F, Glazer NL, Hayward C, Hottenga JJ, Jacobs KB, Knowles JW, Kutalik Z, Monda KL, Polasek O, Preuss M, Rayner NW, Robertson NR, Steinthorsdottir V, Tyrer JP, Voight BF, Wiklund F, Xu J, Zhao JH, Nyholt DR, Pellikka N, Perola M, Perry JR, Surakka I, Tammesoo ML, Altmaier EL, Amin N, Aspelund T, Bhangale T, Boucher G, Chasman DI, Chen C, Coin L, Cooper MN, Dixon AL, Gibson Q, Grundberg E, Hao K, Juhani Junttila M, Kaplan LM, Kettunen J, König IR, Kwan T, Lawrence RW, Levinson DF, Lorentzon M, McKnight B, Morris AP, Müller M, Suh Ngwa J, Purcell S, Rafelt S, Salem RM, Salvi E, Sanna S, Shi J, Sovio U, Thompson JR, Turchin MC, Vandenput L, Verlaan DJ, Vitart V, White CC, Ziegler A, Almgren P, Balmforth AJ, Campbell H, Citterio L, De Grandi A, Dominiczak A, Duan J, Elliott P, Elosua R, Eriksson JG, Freimer NB, Geus EJ, Glorioso N, Haiqing S, Hartikainen AL, Havulinna AS, Hicks AA, Hui J, Igl W, Illig T, Jula A, Kajantie E, Kilpeläinen TO, Koiranen M, Kolcic I, Koskinen S, Kovacs P, Laitinen J, Liu J, Lokki ML, Marusic A, Maschio A, Meitinger T, Mulas A, Paré G, Parker AN, Peden JF, Petersmann A, Pichler I, Pietiläinen KH, Pouta A, Ridderstråle M, Rotter JI, Sambrook JG, Sanders AR, Schmidt CO, Sinisalo J, Smit JH, Stringham HM, Bragi Walters G, Widen E, Wild SH, Willemsen G, Zagato L, Zgaga L, Zitting P, Alavere H, Farrall M, McArdle WL, Nelis M, Peters MJ, Ripatti S, van Meurs JB, Aben KK, Ardlie KG, Beckmann JS, Beilby JP, Bergman RN, Bergmann S, Collins FS, Cusi D, den Heijer M, Eiriksdottir G, Gejman PV, Hall AS, Hamsten A, Huikuri HV, Iribarren C, Kähönen M, Kaprio J, Kathiresan S, Kiemeney L, Kocher T, Launer LJ, Lehtimäki T, Melander O, Mosley TH Jr, Musk AW, Nieminen MS, O'Donnell CJ, Ohlsson C, Oostra B, Palmer LJ, Raitakari O, Ridker PM, Rioux JD, Rissanen A, Rivolta C, Schunkert H, Shuldiner AR, Siscovick DS, Stumvoll M, Tönjes A, Tuomilehto J, van Ommen GJ, Viikari J, Heath AC, Martin NG, Montgomery GW, Province MA, Kayser M, Arnold AM, Atwood LD, Boerwinkle E, Chanock SJ, Deloukas P, Gieger C, Grönberg H, Hall P, Hattersley AT, Hengstenberg C, Hoffman W, Lathrop GM, Salomaa V, Schreiber S, Uda M, Waterworth D, Wright AF, Assimes TL, Barroso I, Hofman A, Mohlke KL, Boomsma DI, Caulfield MJ, Cupples LA, Erdmann J, Fox CS, Gudnason V, Gyllensten U, Harris TB, Hayes RB, Jarvelin MR, Mooser V, Munroe PB, Ouwehand WH, Penninx BW, Pramstaller PP, Quertermous T, Rudan I, Samani NJ, Spector TD, Völzke H, Watkins H, Wilson JF, Groop LC, Haritunians T, Hu FB, Kaplan RC, Metspalu A, North KE, Schlessinger D, Wareham NJ, Hunter DJ, O'Connell JR, Strachan DP, Wichmann HE, Borecki IB, van Duijn CM, Schadt EE, Thorsteinsdottir U, Peltonen L, Uitterlinden AG, Visscher PM, Chatterjee N, Loos RJ, Boehnke M, McCarthy MI, Ingelsson E, Lindgren CM, Abecasis GR, Stefansson K, Frayling TM, and Hirschhorn JN
Subjects: Chromosomes, Human, Pair 3 genetics, Genetic Predisposition to Disease genetics, Genome-Wide Association Study, Humans, Multifactorial Inheritance genetics, Phenotype, Body Height genetics, Genetic Loci genetics, Genome, Human genetics, Metabolic Networks and Pathways genetics, Polymorphism, Single Nucleotide genetics
Abstract: Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
Published: 2010
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32. Breast feeding in infancy and arterial endothelial function later in life. The Cardiovascular Risk in Young Finns Study.

Author: Järvisalo MJ, Hutri-Kähönen N, Juonala M, Mikkilä V, Räsänen L, Lehtimäki T, Viikari J, and Raitakari OT
Subjects: Adult, Age Factors, Birth Weight, Blood Pressure, Brachial Artery diagnostic imaging, Carotid Arteries diagnostic imaging, Cholesterol, Endothelium, Vascular diagnostic imaging, Female, Finland, Humans, Infant, Infant, Newborn, Male, Premature Birth, Regional Blood Flow physiology, Risk Factors, Sex Factors, Smoking, Tunica Intima diagnostic imaging, Tunica Intima physiopathology, Tunica Media diagnostic imaging, Tunica Media physiopathology, Ultrasonography, Vascular Diseases diagnostic imaging, Vasodilation physiology, Waist Circumference, Brachial Artery physiopathology, Breast Feeding, Carotid Arteries physiopathology, Endothelium, Vascular physiopathology, Vascular Diseases physiopathology
Abstract: Background/objectives: Breast feeding in infancy may be associated with reduced cardiovascular morbidity in adulthood. We examined the association between breast feeding in infancy and arterial function and structure in adulthood in a population-based cohort of Finnish adults., Subjects/methods: Noninvasive ultrasound was used to measure brachial artery flow-mediated dilatation (FMD), carotid artery intima-media thickness (IMT) and carotid artery compliance (CAC) in 1667 young adults participating in the Cardiovascular Risk in Young Finns Study with data on early nutrition., Results: Maximal FMD was higher in breast-fed men compared to formula-fed men (7.2+/-4.0 vs 5.9+/-3.4%, P=0.029) while no differences were seen between breast-fed and formula-fed women (8.9+/-4.5 vs 8.8+/-5.0%, P=0.84). In men, the multivariable correlates of FMD included the group variable for breast feeding (P=0.014), birth weight (P=0.043), waist circumference (P<0.001) and baseline brachial artery diameter (P<0.001). In women, the multivariable correlates of FMD were birth weight (P=0.02), waist circumference (P<0.001) and brachial artery baseline diameter (P<0.001). Breast feeding was not significantly associated with IMT or CAC in multivariable models., Conclusions: Adult men who have been breast fed have better brachial endothelial function compared to men who have been formula fed.
Published: 2009
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32 results on '"Raitakari, O."'

1. Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson's disease

2. GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

3. Carotid artery compliance in users of plant stanol ester margarine

4. Longitudinal changes in diet from childhood into adulthood with respect to risk of cardiovascular diseases: The Cardiovascular Risk in Young Finns Study

5. Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error

6. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

7. Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

8. Defining the role of common variation in the genomic and biological architecture of adult human height

9. Hostility in adolescents and adults

10. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

11. Hundreds of variants clustered in genomic loci and biological pathways affect human height

12. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

13. Associations of active commuting to school in childhood and physical activity in adulthood.

14. A new blood based epigenetic age predictor for adolescents and young adults.

15. Long-term residential sunlight exposure associated with cognitive function among adults residing in Finland.

16. Adulthood blood levels of hsa-miR-29b-3p associate with preterm birth and adult metabolic and cognitive health.

17. Examining the effect of mitochondrial DNA variants on blood pressure in two Finnish cohorts.

18. HDL cholesterol efflux capacity is inversely associated with subclinical cardiovascular risk markers in young adults: The cardiovascular risk in Young Finns study.

19. Whole blood microRNA levels associate with glycemic status and correlate with target mRNAs in pathways important to type 2 diabetes.

20. The effect of apolipoprotein E polymorphism on serum metabolome - a population-based 10-year follow-up study.

21. Circulating metabolic biomarkers of renal function in diabetic and non-diabetic populations.

22. Fatty liver is associated with blood pathways of inflammatory response, immune system activation and prothrombotic state in Young Finns Study.

23. Association of circulating metabolites with healthy diet and risk of cardiovascular disease: analysis of two cohort studies.

24. Effects of childhood and adolescence physical activity patterns on psychosis risk-a general population cohort study.

25. Blood hsa-miR-122-5p and hsa-miR-885-5p levels associate with fatty liver and related lipoprotein metabolism-The Young Finns Study.

26. Genome-wide association study identifies 74 loci associated with educational attainment.

27. Directional dominance on stature and cognition in diverse human populations.

28. Vigorous physical activity and carotid distensibility in young and mid-aged adults.

29. Seventy-five genetic loci influencing the human red blood cell.

30. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

31. Hundreds of variants clustered in genomic loci and biological pathways affect human height.

32. Breast feeding in infancy and arterial endothelial function later in life. The Cardiovascular Risk in Young Finns Study.

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32 results on '"Raitakari, O."'

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