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8 results on '"Uzma Afzal"'

1. The genetic architecture of type 2 diabetes

Author

Clement Ma, Liisa Hakaste, Claes Ladenvall, Massimo Mangino, Lars Lind, Aaron G. Day-Williams, Ryan Poplin, Thomas Schwarzmayr, Annette Peters, Thomas Meitinger, Satish Kumar, Kyong Soo Park, Ching-Yu Cheng, Farook Thameem, Kyle J. Gaulton, Olov Rolandsson, Yossi Farjoun, Neil Robertson, Mauricio O. Carneiro, Mark A. DePristo, Pierre Fontanillas, Ruth J. F. Loos, Heather M. Highland, Vilmantas Giedraitis, Gemma Buck, Fredrik Karpe, Mohammad Kamran Ikram, Alex S. F. Doney, Hae Kyung Im, Eric S. Lander, Johanna Kuusisto, Dorothée Thuillier, Denis Rybin, Jacquelyn Murphy, Benjamin M. Neale, Martina Müller-Nurasyid, Eric R. Gamazon, Johanne Marie Justesen, Tin Aung, Vincent K. L. Lam, John Danesh, Donna M. Lehman, Goo Jun, Marit E. Jørgensen, Christian Herder, Edmund Chan, Pamela J. Hicks, Todd Green, Claudia Langenberg, Yoon Shin Cho, James G. Wilson, Daniel E. Hale, Rector Arya, Giriraj R. Chandak, Juan Fernandez Tajes, Jaakko Tuomilehto, Christopher P. Jenkinson, Anders Rosengren, Torsten Lauritzen, Michael Griswold, Karen L. Mohlke, Amy J. Swift, Alena Stančáková, Christian Fuchsberger, Iksoo Huh, Nikhil Tandon, João Fadista, Christa Meisinger, Gonçalo R. Abecasis, Pål R. Njølstad, Dwaipayan Bharadwaj, Richard M. Watanabe, Shaun Purcell, Veikko Salomaa, Tim D. Spector, Paul W. Franks, Adam E. Locke, Sharon P. Fowler, Panos Deloukas, Reedik Mägi, Solomon K. Musani, Kee Seng Chia, Barbara Thorand, Soo Heon Kwak, Annemari Käräjämäki, Evelin Mihailov, John Blangero, Thomas Wieland, Christian Gieger, E. Shyong Tai, Jianjun Liu, James B. Meigs, Teemu Kuulasmaa, Martin Hrabé de Angelis, Francis S. Collins, Tim M. Strom, Tibor V. Varga, Juyoung Lee, Mark I. McCarthy, Domenico Palli, Jong-Young Lee, Benjamin Glaser, Tasha E. Fingerlin, Stephen O'Rahilly, Andrew T. Hattersley, Gil Atzmon, Manuel A. Rivas, Noël P. Burtt, Ivan Brandslund, Young-Jin Kim, Dorairaj Prabhakaran, Xu Wang, Taylor J. Maxwell, Valeriya Lyssenko, Frank B. Hu, Adolfo Correa, Khalid Shakir, Kathleen A. Jablonski, Yingchang Lu, Wei-Yen Lim, Min Jin Go, William R. Scott, Hanna E. Abboud, Leena Kinnunen, Inês Barroso, Gabriela L. Surdulescu, Peng Chen, Robert Sladek, Marju Orho-Melander, Xueling Sim, Robert A. Scott, Joanna M. M. Howson, Markku Laakso, David Altshuler, Vidya S. Farook, Harald Grallert, Janina S. Ried, Vineeta Agarwala, Philippe Froguel, Nicholas J. Wareham, Tiinamaija Tuomi, Joon Yoon, Heikki A. Koistinen, Toni I. Pollin, Heiner Boeing, Marie Loh, Nicola L. Beer, Joanne E. Curran, Lars Lannfelt, Dorota Pasko, Taesung Park, David Buck, Nir Barzilai, Stephen C. J. Parker, Michael Roden, Bok-Ghee Han, David Aguilar, Timothy Fennell, Sian-Tsung Tan, Gregory P. Wilson, Momoko Horikoshi, Cramer Christensen, Craig L. Hanis, Gilean McVean, Benjamin F. Voight, Wolfgang Rathmann, Jared Maguire, Ashok Kumar, Donald W. Bowden, Michael L. Stitzel, Yongkang Kim, Christine Blancher, Jason Carey, Min-Seok Kwon, Nicholette D. Palmer, Oluf Pedersen, Niels Grarup, Peter S. Chines, Cornelia Huth, James Scott, Torben Hansen, Konstantin Strauch, Erwin P. Bottinger, Andrew D. Morris, Anette P. Gjesing, Erik Ingelsson, Colin N. A. Palmer, Claudia H. T. Tam, Stacey Gabriel, Pablo Cingolani, Beverley Balkau, Michael Boehnke, Peter M. Nilsson, Wing-Yee So, Andrew R. Wood, Lili Milani, Ravindranath Duggirala, Qibin Qi, Mark Walker, Weiping Jia, Mark Seielstad, Narisu Narisu, Tien Yin Wong, Martijn van de Bunt, Anubha Mahajan, Davis J. McCarthy, Ann-Christine Syvänen, Jennifer Kriebel, N. William Rayner, Han Chen, Jinyan Huang, Chiea Chuen Khor, Richard N. Bergman, Shah Ebrahim, Dylan Hodgkiss, Weihua Zhang, Manjinder S. Sandhu, Richard D. Pearson, Juliana C.N. Chan, Rainer Rauramaa, Ralph A. DeFronzo, Andrew Farmer, Yoshihiko Nagai, Allan Linneberg, Herman A. Taylor, Jose C. Florez, Jaspal S. Kooner, Lori L. Bonnycastle, Jeroen R. Huyghe, Leif Groop, Joseph Trakalo, Sobha Puppala, Bong-Jo Kim, Kathleen Stirrups, Kerrin S. Small, Cecilia M. Lindgren, Jennifer E. Below, Heung Man Lee, Inga Prokopenko, Liming Liang, Timothy M. Frayling, Uzma Afzal, Mark J. Daly, Yik Ying Teo, Andrew P. Morris, Phoenix Kwan, Yvonne T. van der Schouw, Cheng Hu, Katharine R. Owen, Alisa K. Manning, Christopher J. Groves, Josée Dupuis, Ryan P. Welch, Loukas Moutsianas, Joshua D. Smith, Tanya M. Teslovich, Robert C. Onofrio, Maggie C.Y. Ng, Peter Donnelly, Tõnu Esko, Matt Neville, Bo Isomaa, Anne U. Jackson, Jette Bork-Jensen, Barry I. Freedman, Yi Chen, Danish Saleheen, Lu Qi, Laura J. Scott, Jasmina Kravic, Paul Elliott, Mette Hollensted, Carmen Navarro, Selyeong Lee, Benjamin Lehne, Thomas Illig, Nancy J. Cox, Jonathan C. Levy, George B. Grant, John C. Chambers, Adam S. Butterworth, Ronald C.W. Ma, Teresa Ferreira, John R. B. Perry, Eleftheria Zeggini, Hyun Min Kang, Loic Yengo, Eric Banks, Jae-Hoon Lee, Anna L. Gloyn, Christopher Hartl, Wei Zhao, Andres Metspalu, Keng-Han Lin, Graeme I. Bell, Jason Flannick, Torben Jørgensen, Thomas W. Blackwell, Heather M. Stringham, Olle Melander, Omri Gottesman, Other departments, British Heart Foundation, Wellcome Trust, Medical Research Council (MRC), Massachusetts Institute of Technology. Department of Biology, Altshuler, David M, Internal Medicine, Perry, John [0000-0001-6483-3771], Butterworth, Adam [0000-0002-6915-9015], Howson, Joanna [0000-0001-7618-0050], Danesh, John [0000-0003-1158-6791], Johnson, Kathleen [0000-0002-6823-3252], O'Rahilly, Stephen [0000-0003-2199-4449], Langenberg, Claudia [0000-0002-5017-7344], Sandhu, Manjinder [0000-0002-2725-142X], Barroso, Ines [0000-0001-5800-4520], Wareham, Nicholas [0000-0003-1422-2993], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, PROTEIN INTERACTION NETWORKS, SUSCEPTIBILITY LOCI, Genotyping Techniques, General Science & Technology, DNA Mutational Analysis, SEQUENCING ASSOCIATION, 030209 endocrinology & metabolism, Genome-wide association study, Biology, Research Support, N.I.H, 03 medical and health sciences, 0302 clinical medicine, Research Support, N.I.H., Extramural, SDG 3 - Good Health and Well-being, MD Multidisciplinary, Genetic predisposition, Journal Article, Humans, Exome, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Non-U.S. Gov't, Exome sequencing, Alleles, Genetic association, Genetics, RISK, Multidisciplinary, HERITABILITY, Research Support, Non-U.S. Gov't, COMPLEX TRAITS, Extramural, Genetic Variation, Genetic architecture, HUMAN-DISEASE, Europe, 030104 developmental biology, Diabetes Mellitus, Type 2, RARE VARIANTS, Sample Size, LOW-FREQUENCY, Imputation (genetics), Common disease-common variant, Genome-Wide Association Study
Abstract

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.

Published
2016

2. Epigenome-wide association of DNA methylation markers in peripheral blood from Indian Asians and Europeans with incident type 2 diabetes: a nested case-control study

Author

Christian Gieger, Timothy J. Aitman, John Danesh, Danish Saleheen, Anuradhani Kasturiratne, Soterios A. Kyrtopoulos, Antti J. Kangas, James Scott, Gianluca Campanella, Sujeet Jha, Jeremy B. M. Jowett, Hannah R Elliott, Paul Elliott, Loic Yengo, Ole Ammerpohl, Marjo-Riitta Järvelin, Pasi Soininen, Marc Chadeau-Hyam, Benjamin Lehne, Janne Pitkäniemi, Simon de Lusignan, Weihua Zhang, Barbara Thorand, Christian Herder, Mark I. McCarthy, Simone Wahl, James Abbott, Mika Ala-Korpela, Thomas Illig, Martyna Adamowicz-Brice, Stéphane Cauchi, Tom R. Gaunt, Alexander W. Drong, Norihiro Kato, Philippe Froguel, Ananda R. Wickremasinghe, Jochen Hampe, Harald Grallert, Sian-Tsung Tan, Jennifer Kriebel, Richie Soong, Paolo Vineis, Holger Prokisch, Navaratnam Kotea, Caroline L Relton, Michelle Ann Rozario, Simon Jones, Letizia Tarantini, John C. Chambers, Prakash P Punjabi, Hong Kiat Ng, Sudhir Kowlessur, Rebecca C Richmond, Valeria Motta, William R. Scott, R. Caiazzo, Benedetta Albetti, Valentina Bollati, Jaakko Tuomilehto, Zuan Yu Mok, Uzma Afzal, Kiymet Bozaoglu, Jaspal S. Kooner, Federica Rota, Clemens Schafmayer, Marie Loh, François Pattou, E-Shyong Tai, Pier Alberto Bertazzi, Christine Blancher, British Heart Foundation, Medical Research Council (MRC), Wellcome Trust, National Institute for Health Research, and Action on Hearing Loss

Subjects
Male, STRESS, Endocrinology, Diabetes and Metabolism, PROTEIN, Type 2 diabetes, GLUCOSE, Epigenesis, Genetic, MELLITUS, 0302 clinical medicine, Endocrinology, Risk Factors, Prospective Studies, media_common, 2. Zero hunger, INSULIN-RESISTANCE, 0303 health sciences, education.field_of_study, Incidence (epidemiology), Middle Aged, 3. Good health, CARBOHYDRATE RESPONSE ELEMENT, OBESITY, Female, Life Sciences & Biomedicine, EXPRESSION, Asian Continental Ancestry Group, Genetic Markers, SUSCEPTIBILITY LOCI, European Continental Ancestry Group, Population, 030209 endocrinology & metabolism, Article, White People, Endocrinology & Metabolism, 03 medical and health sciences, INFLAMMATION, Asian People, Diabetes mellitus, Internal Medicine, medicine, Humans, media_common.cataloged_instance, European union, education, 030304 developmental biology, Science & Technology, business.industry, Case-control study, DNA Methylation, medicine.disease, Obesity, Diabetes Mellitus, Type 2, Case-Control Studies, Nested case-control study, business, Genome-Wide Association Study, Demography
Abstract

Background Indian Asians, who make up a quarter of the world's population, are at high risk of developing type 2 diabetes. We investigated whether DNA methylation is associated with future type 2 diabetes incidence in Indian Asians and whether differences in methylation patterns between Indian Asians and Europeans are associated with, and could be used to predict, differences in the magnitude of risk of developing type 2 diabetes. Methods We did a nested case-control study of DNA methylation in Indian Asians and Europeans with incident type 2 diabetes who were identified from the 8-year follow-up of 25 372 participants in the London Life Sciences Prospective Population (LOLIPOP) study. Patients were recruited between May 1, 2002, and Sept 12, 2008. We did epigenome-wide association analysis using samples from Indian Asians with incident type 2 diabetes and age-matched and sex-matched Indian Asian controls, followed by replication testing of top-ranking signals in Europeans. For both discovery and replication, DNA methylation was measured in the baseline blood sample, which was collected before the onset of type 2 diabetes. Epigenome-wide significance was set at p

Published
2015

3. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Author

P. Eline Slagboom, Massimo Mangino, David J. Porteous, Karin Leander, Nancy L. Heard-Costa, Sharon L.R. Kardia, Jennifer Bragg, Ken K. Ong, Igor Rudan, Blair H. Smith, Mark A. Sarzynski, Torben Hansen, James F. Wilson, Weihua Zhang, Zoltán Kutalik, Karl Gertow, Yii-Der Ida Chen, Daniele Cusi, Lu Qi, Nicholas G. Martin, Peter Vollenweider, Thomas W. Winkler, Graciela E. Delgado, Thorkild I. A. Sørensen, André G. Uitterlinden, J. Wouter Jukema, Rajesh Rawal, Dena G. Hernandez, Amy J. Swift, Naveed Sattar, Ruth J. F. Loos, George Dedoussis, Ani Manichaikul, Henrik Vestergaard, Jian'an Luan, Luting Xue, Charles Kooperberg, Rona J. Strawbridge, John-Olov Jansson, Jian Gong, Martina Müller-Nurasyid, L. Adrienne Cupples, Frida Renström, Stephan J. L. Bakker, Ivana Kolcic, Mathias Gorski, Tamara B. Harris, Sandosh Padmanabhan, Stephanie A. Bien, Arthur W. Musk, Cristina Menni, Steve Buyske, Anubha Mahajan, Claudia Schurmann, John Blangero, Natalia Pervjakova, Inês Barroso, Kristin L. Young, Momoko Horikoshi, Robert A. Scott, Ozren Polasek, Shafqat Ahmad, Jeremiah Perez, Stella Trompet, Claude Bouchard, Claudia Langenberg, Paul M. Ridker, Tuomas O. Kilpeläinen, Oddgeir L. Holmen, Tarunveer S. Ahluwalia, Alan F. Wright, Ulf de Faire, Cecilia M. Lindgren, Misa Graff, Jie Huang, Liesbeth Vandenput, Marcel Bruinenberg, Luigi Ferrucci, Johanne Marie Justesen, Audrey Y. Chu, Melanie Waldenberger, Karen L. Mohlke, Ching-Ti Liu, Barbara Thorand, Joseph Hung, Pim van der Harst, Colin A. McKenzie, Sailaja Vedantam, Gitta H. Lubke, Bruna Gigante, Göran Hallmans, Sara Lupoli, Anja Ludolph-Donislawski, Michael Boehnke, Treva Rice, Lori L. Bonnycastle, Daniele Braga, Mika Kähönen, Joel Eriksson, Gonçalo R. Abecasis, Joseph M. Wu, Niels Grarup, Ilja M. Nolte, Jonathan Marchini, Georg Homuth, Pamela A. F. Madden, John Beilby, Andrew D. Johnson, Nanette R. Lee, Caroline Hayward, Unhee Lim, Bamidele O. Tayo, Peter S. Chines, Lynda M. Rose, Amélie Bonnefond, Elena Tremoli, Serena Sanna, David P. Strachan, Barbara McKnight, Narisu Narisu, Anton J. M. de Craen, David R. Weir, Albertine J. Oldehinkel, Jessica Tyrrell, Beverley Balkau, Kirsti Kvaløy, Marie-Claude Vohl, Jennifer A. Smith, Rainer Rauramaa, Andrew C. Heath, Erwin P. Bottinger, Andrew Wong, Günther Silbernagel, Mattias Lorentzon, Philippe Froguel, Uzma Afzal, Tanja B. Grammer, Dabeeru C. Rao, Charlotta Pisinger, Nicola Glorioso, Najaf Amin, Andrew P. Morris, Tanguy Corre, Alan James, Julius S. Ngwa, Jennifer E. Huffman, Gudny Eiriksdottir, Maija Hassinen, Lenore J. Launer, Marit E. Jørgensen, Dorret I. Boomsma, Harry Campbell, Scott Coggeshall, Timothy M. Frayling, Konstantin Strauch, Johanna Kuusisto, David Hadley, Penny Gordon-Larsen, Xuan Deng, Dorothée Thuillier, Albert V. Smith, Jaakko Tuomilehto, Harald Grallert, Lynne J. Hocking, Dan Mellström, M. Carola Zillikens, Lars Lind, Hester M. den Ruijter, Gemma Cadby, Joanne E. Curran, Richard N. Bergman, David J. Stott, Matthias Olden, Veronique Vitart, Robert Luben, Cinzia Sarti, Gert J. de Borst, Lyle J. Palmer, Sven Bergmann, Alexander Teumer, John D. Eicher, Marcus E. Kleber, Marie Loh, Genovefa Kolovou, Iris M. Heid, Gonneke Willemsen, Marie Neergaard Harder, David J. Hunter, Stefania Bandinelli, Francis S. Collins, Hans J. Grabe, Virginia Fisher, John Whitfield, Leo-Pekka Lyytikäinen, Salome Scholtens, Tamuno Alfred, Richard S. Cooper, Jouke-Jan Hottenga, Martina Chittani, Jan A. Staessen, Bernhard K. Krämer, Markku Laakso, Min A. Jhun, Marjo-Riitta Järvelin, Saima Afaq, Rita P. S. Middelberg, Jing Hua Zhao, Toshiko Tanaka, Kent D. Taylor, Rudi G. J. Westendorp, Panagiotis Deloukas, Nina Hutri-Kähönen, Reiner Biffar, Krista Fischer, Leena Kinnunen, Diana Kuh, Jaspal S. Kooner, Caroline S. Fox, Harold Snieder, Pau Navarro, Stéphane Lobbens, Tao Huang, Vilmundur Gudnason, Jacqueline M. Vink, Terrence Forrester, Kari E. North, Annette Peters, Mika Kivimäki, David Schlessinger, Ian Ford, Kristian Hveem, Christopher A. Haiman, Lucia A. Hindorff, Oluf Pedersen, Ingrid B. Borecki, Bruce H. R. Wolffenbuttel, Nicholas J. Wareham, Cornelia M. van Duijn, Lawrence F. Bielak, Loic Le Marchand, Linda S. Adair, Tõnu Esko, Anne U. Jackson, Ying Wu, Eco J. C. de Geus, Jana V. van Vliet-Ostaptchouk, Louis Pérusse, Peter J. van der Most, Ulrike Peters, Magnus Karlsson, Anders Hamsten, Anne E. Justice, Alena Stančáková, Henning Tiemeier, Eric Boerwinkle, Catharina A. Hartman, Claes Ohlsson, Grant W. Montgomery, Elise Lim, Traci M. Bartz, Erik Ingelsson, Martina E. Zimmermann, Laura J. Rasmussen-Torvik, Terho Lehtimäki, Heikki A. Koistinen, Pirjo Komulainen, Damiano Baldassarre, Marten A. Siemelink, Niek Verweij, Gerard Pasterkamp, Markus Juonala, Wei Zhao, Andres Metspalu, Sander W. van der Laan, Tuomo Rankinen, Timo A. Lakka, Yun Ju Sung, Heather M. Stringham, Bruce M. Psaty, Niha Zubair, Stavroula Kanoni, Saskia Haitjema, Bengt Sennblad, Llilda Barata, Morris A. Swertz, Mary F. Feitosa, Tim D. Spector, Paul W. Franks, Qibin Qi, Francesco Cucca, Allan Linneberg, Reija Männikkö, Jonathan Marten, Olli T. Raitakari, Mark I. McCarthy, Joel N. Hirschhorn, Winfried März, Sarah H. Wild, Meena Kumari, Nese Direk, Patricia A. Peyser, Jessica D. Faul, John C. Chambers, Nicholas D. Hastie, Mette Hollensted, Jacek Czajkowski, Daniel I. Chasman, Matthias Nauck, Gérard Waeber, Brendan M. Buckley, Kai Savonen, Judith M. Vonk, Carsten A. Böger, Loic Yengo, Anna Eriksson, Henry Völzke, Pedro Marques-Vidal, Center for Liver, Digestive and Metabolic Diseases (CLDM), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Research Institute for Asthma and COPD (GRIAC), Cardiovascular Centre (CVC), Clinicum, Department of Medicine, University of Helsinki, Endokrinologian yksikkö, HUS Internal Medicine and Rehabilitation, Luan, Jian'an [0000-0003-3137-6337], Marten, Jonathan [0000-0001-6916-2014], Langenberg, Claudia [0000-0002-5017-7344], Luben, Robert [0000-0002-5088-6343], Ong, Kenneth [0000-0003-4689-7530], Wareham, Nicholas [0000-0003-1422-2993], Barroso, Ines [0000-0001-5800-4520], Apollo - University of Cambridge Repository, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Biological Psychology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, APH - Methodology, APH - Personalized Medicine, Epidemiology, Erasmus MC other, Medical Microbiology & Infectious Diseases, Internal Medicine, Child and Adolescent Psychiatry / Psychology, and Psychiatry

Subjects
0301 basic medicine, Netherlands Twin Register (NTR), Medicin och hälsovetenskap, Offita, Chemistry(all), Epidemiology, General Physics and Astronomy, Genome-wide association study, methods [Genome-Wide Association Study], Biochemistry, Genome-wide association studies, Medical and Health Sciences, Body Mass Index, genetics [Obesity], Genetics research, IMPUTATION, Body Fat Distribution, genetics [Genetic Predisposition to Disease], OXIDATIVE STRESS, POPULATION, Adiposity, METABOLIC SYNDROME, Genetics, education.field_of_study, Multidisciplinary, Smoking, Public Health, Global Health, Social Medicine and Epidemiology, genetics [Smoking], ASSOCIATION, 3142 Public health care science, environmental and occupational health, 3. Good health, Multidisciplinary Sciences, DEFICIENCY, Phenotype, ADDICTION, Science & Technology - Other Topics, Medical genetics, ddc:500, Waist Circumference, Reykingar, genetics [Adiposity], Adult, medicine.medical_specialty, Science, Quantitative Trait Loci, Population, genetics [Waist Circumference], Accounting, Biology, Quantitative trait locus, Physics and Astronomy(all), Polymorphism, Single Nucleotide, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, SDG 3 - Good Health and Well-being, GWAS, obesity, smoking, MD Multidisciplinary, Genetic predisposition, medicine, Journal Article, Erfðafræði, Humans, Genetic Predisposition to Disease, Obesity, education, Genetic association, Science & Technology, VITAMIN-C, genetics [Quantitative Trait Loci], Waist-Hip Ratio, business.industry, Biochemistry, Genetics and Molecular Biology(all), Epistasis, Genetic, Rannsóknir, General Chemistry, ta3121, R1, GENE, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, MICE, 030104 developmental biology, 3121 General medicine, internal medicine and other clinical medicine, business, Body mass index, Developmental Psychopathology, Imputation (genetics), Genetics and Molecular Biology(all), Genome-Wide Association Study
Abstract

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution., A full list of acknowledgments appears in the Supplementary Note 4. Co-author A.J.M.d.C. recently passed away while this work was in process. This work was performed under the auspices of the Genetic Investigation of ANthropometric Traits (GIANT) consortium. We acknowledge the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium for encouraging CHARGE studies to participate in this effort and for the contributions of CHARGE members to the analyses conducted for this research. Funding for this study was provided by the Aase and Ejner Danielsens Foundation; Academy of Finland (41071, 77299, 102318, 110413, 117787, 121584, 123885, 124243, 124282, 126925, 129378, 134309, 286284); Accare Center for Child and Adolescent Psychiatry; Action on Hearing Loss (G51); Agence Nationale de la 359 Recherche; Agency for Health Care Policy Research (HS06516); ALF/LUA research grant in Gothenburg; ALFEDIAM; ALK-Abelló A/S; Althingi; American Heart Association (13POST16500011); Amgen; Andrea and Charles Bronfman Philanthropies; Ardix Medical; Arthritis Research UK; Association Diabète Risque Vasculaire; Australian National Health and Medical Research Council (241944, 339462, 389875, 389891, 389892, 389927, 389938, 442915, 442981, 496739, 552485, 552498); Avera Institute; Bayer Diagnostics; Becton Dickinson; BHF (RG/14/5/30893); Boston Obesity Nutrition Research Center (DK46200), Bristol-Myers Squibb; British Heart Foundation (RG/10/12/28456, RG2008/08, RG2008/014, SP/04/002); Medical Research Council of Canada; Canadian Institutes for Health Research (FRCN-CCT-83028); Cancer Research UK; Cardionics; Cavadis B.V., Center for Medical Systems Biology; Center of Excellence in Genomics; CFI; CIHR; City of Kuopio; CNAMTS; Cohortes Santé TGIR; Contrat de Projets État-Région; Croatian Science Foundation (8875); Danish Agency for Science, Technology and Innovation; Danish Council for Independent Research (DFF-1333-00124, DFF-1331-00730B); County Council of Dalarna; Dalarna University; Danish Council for Strategic Research; Danish Diabetes Academy; Danish Medical Research Council; Department of Health, UK; Development Fund from the University of Tartu (SP1GVARENG); Diabetes Hilfs- und Forschungsfonds Deutschland; Diabetes UK; Diabetes Research and Wellness Foundation Fellowship; Donald W. Reynolds Foundation; Dr Robert Pfleger-Stiftung; Dutch Brain Foundation; Dutch Diabetes Research Foundation; Dutch Inter University Cardiology Institute; Dutch Kidney Foundation (E033); Dutch Ministry of Justice; the DynaHEALTH action No. 633595, Economic Structure Enhancing Fund of the Dutch Government; Else Kröner-Fresenius-Stiftung (2012_A147, P48/08//A11/08); Emil Aaltonen Foundation; Erasmus University Medical Center Rotterdam; Erasmus MC and Erasmus University Rotterdam; the Municipality of Rotterdam; Estonian Government (IUT20-60, IUT24-6); Estonian Research Roadmap through the Estonian Ministry of Education and Research (3.2.0304.11-0312); European Research Council (ERC Starting Grant and 323195:SZ-245 50371-GLUCOSEGENES-FP7-IDEAS-ERC); European Regional Development Fund; European Science Foundation (EU/QLRT-2001-01254); European Commission (018947, 018996, 201668, 223004, 230374, 279143, 284167, 305739, BBMRI-LPC-313010, HEALTH-2011.2.4.2-2-EU-MASCARA, HEALTH-2011-278913, HEALTH-2011-294713-EPLORE, HEALTH-F2-2008-201865-GEFOS, HEALTH-F2-2013-601456, HEALTH-F4-2007-201413, HEALTH-F4-2007-201550-HYPERGENES, HEALTH-F7-305507 HOMAGE, IMI/115006, LSHG-CT-2006-018947, LSHG-CT-2006-01947, LSHM-CT-2004-005272, LSHM-CT-2006-037697, LSHM-CT-2007-037273, QLG1-CT-2002-00896, QLG2-CT-2002-01254); Faculty of Biology and Medicine of Lausanne; Federal Ministry of Education and Research (01ZZ0103, 01ZZ0403, 01ZZ9603, 03IS2061A, 03ZIK012); Federal State of Mecklenburg-West Pomerania; Fédération Française de Cardiologie; Finnish Cultural Foundation; Finnish Diabetes Association; Finnish Foundation of Cardiovascular Research; Finnish Heart Association; Fondation Leducq; Food Standards Agency; Foundation for Strategic Research; French Ministry of Research; FRSQ; Genetic Association Information Network (GAIN) of the Foundation for the NIH; German Federal Ministry of Education and Research (BMBF, 01ER1206, 01ER1507); GlaxoSmithKline; Greek General Secretary of Research and Technology; Göteborg Medical Society; Health and Safety Executive; Healthcare NHS Trust; Healthway; Western Australia; Heart Foundation of Northern Sweden; Helmholtz Zentrum München—German Research Center for Environmental Health; Hjartavernd; Ingrid Thurings Foundation; INSERM; InterOmics (PB05 MIUR-CNR); INTERREG IV Oberrhein Program (A28); Interuniversity Cardiology Institute of the Netherlands (ICIN, 09.001); Italian Ministry of Health (ICS110.1/RF97.71); Italian Ministry of Economy and Finance (FaReBio di Qualità); Marianne and Marcus Wallenberg Foundation; the Ministry of Health, Welfare and Sports, the Netherlands; J.D.E. and Catherine T, MacArthur Foundation Research Networks on Successful Midlife Development and Socioeconomic Status and Health; Juho Vainio Foundation; Juvenile Diabetes Research Foundation International; KfH Stiftung Präventivmedizin e.V.; King's College London; Knut and Alice Wallenberg Foundation; Kuopio University Hospital; Kuopio, Tampere and Turku University Hospital Medical Funds (X51001); La Fondation de France; Leenaards Foundation; Lilly; LMUinnovativ; Lundberg Foundation; Magnus Bergvall Foundation; MDEIE; Medical Research Council UK (G0000934, G0601966, G0700931, MC_U106179471, MC_UU_12019/1); MEKOS Laboratories; Merck Santé; Ministry for Health, Welfare and Sports, The Netherlands; Ministry of Cultural Affairs of Mecklenburg-West Pomerania; Ministry of Economic Affairs, The Netherlands; Ministry of Education and Culture of Finland (627;2004-2011); Ministry of Education, Culture and Science, The Netherlands; Ministry of Science, Education and Sport in the Republic of Croatia (108-1080315-0302); MRC centre for Causal Analyses in Translational Epidemiology; MRC Human Genetics Unit; MRC-GlaxoSmithKline pilot programme (G0701863); MSD Stipend Diabetes; National Institute for Health Research; Netherlands Brain Foundation (F2013(1)-28); Netherlands CardioVascular Research Initiative (CVON2011-19); Netherlands Genomics Initiative (050-060-810); Netherlands Heart Foundation (2001 D 032, NHS2010B280); Netherlands Organization for Scientific Research (NWO) and Netherlands Organisation for Health Research and Development (ZonMW) (56-464-14192, 60-60600-97-118, 100-001-004, 261-98-710, 400-05-717, 480-04-004, 480-05-003, 481-08-013, 904-61-090, 904-61-193, 911-11-025, 985-10-002, Addiction-31160008, BBMRI–NL 184.021.007, GB-MaGW 452-04-314, GB-MaGW 452-06-004, GB-MaGW 480-01-006, GB-MaGW 480-07-001, GB-MW 940-38-011, Middelgroot-911-09-032, NBIC/BioAssist/RK 2008.024, Spinozapremie 175.010.2003.005, 175.010.2007.006); Neuroscience Campus Amsterdam; NHS Foundation Trust; National Institutes of Health (1RC2MH089951, 1Z01HG000024, 24152, 263MD9164, 263MD821336, 2R01LM010098, 32100-2, 32122, 32108, 5K99HL130580-02, AA07535, AA10248, AA11998, AA13320, AA13321, AA13326, AA14041, AA17688, AG13196, CA047988, DA12854, DK56350, DK063491, DK078150, DK091718, DK100383, DK078616, ES10126, HG004790, HHSN268200625226C, HHSN268200800007C, HHSN268201200036C, HHSN268201500001I, HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C, HL043851, HL45670, HL080467, HL085144, HL087660, HL054457, HL119443, HL118305, HL071981, HL034594, HL126024, HL130114, KL2TR001109, MH66206, MH081802, N01AG12100, N01HC55015, N01HC55016, N01C55018, N01HC55019, N01HC55020, N01HC55021, N01HC55022, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, N01HC95159, N01HC95160, N01HC95161, N01HC95162, N01HC95163, N01HC95164, N01HC95165, N01HC95166, N01HC95167, N01HC95168, N01HC95169, N01HG65403, N01WH22110, N02HL6‐4278, N01-HC-25195, P01CA33619, R01HD057194, R01HD057194, R01AG023629, R01CA63, R01D004215701A, R01DK075787, R01DK062370, R01DK072193, R01DK075787, R01DK089256, R01HL53353, R01HL59367, R01HL086694, R01HL087641, R01HL087652, R01HL103612, R01HL105756, R01HL117078, R01HL120393, R03 AG046389, R37CA54281, RC2AG036495, RC4AG039029, RPPG040710371, RR20649, TW008288, TW05596, U01AG009740, U01CA98758, U01CA136792, U01DK062418, U01HG004402, U01HG004802, U01HG007376, U01HL080295, UL1RR025005, UL1TR000040, UL1TR000124, UL1TR001079, 2T32HL007055-36, T32GM074905, HG002651, HL084729, N01-HC-25195, UM1CA182913); NIH, National Institute on Aging (Intramural funding, NO1-AG-1-2109); Northern Netherlands Collaboration of Provinces; Novartis Pharma; Novo Nordisk; Novo Nordisk Foundation; Nutricia Research Foundation (2016-T1); ONIVINS; Parnassia Bavo group; Pierre Fabre; Province of Groningen; Päivikki and Sakari Sohlberg Foundation; Påhlssons Foundation; Paavo Nurmi Foundation; Radboud Medical Center Nijmegen; Research Centre for Prevention and Health, the Capital Region of Denmark; the Research Institute for Diseases in the Elderly; Research into Ageing; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center; Roche; Royal Society; Russian Foundation for Basic Research (NWO-RFBR 047.017.043); Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06); Sanofi-Aventis; Scottish Government Health Directorates, Chief Scientist Office (CZD/16/6); Siemens Healthcare; Social Insurance Institution of Finland (4/26/2010); Social Ministry of the Federal State of Mecklenburg-West Pomerania; Société Francophone du 358 Diabète; State of Bavaria; Stiftelsen för Gamla Tjänarinnor; Stockholm County Council (560183, 592229); Strategic Cardiovascular and Diabetes Programmes of Karolinska Institutet and Stockholm County Council; Stroke Association; Swedish Diabetes Association; Swedish Diabetes Foundation (2013-024); Swedish Foundation for Strategic Research; Swedish Heart-Lung Foundation (20120197, 20150711); Swedish Research Council (0593, 8691, 2012-1397, 2012-1727, and 2012-2215); Swedish Society for Medical Research; Swiss Institute of Bioinformatics; Swiss National Science Foundation (3100AO-116323/1, 31003A-143914, 33CSCO-122661, 33CS30-139468, 33CS30-148401, 51RTP0_151019); Tampere Tuberculosis Foundation; Technology Foundation STW (11679); The Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community (G.0880.13, G.0881.13); The Great Wine Estates of the Margaret River Region of Western Australia; Timber Merchant Vilhelm Bangs Foundation; Topcon; Tore Nilsson Foundation; Torsten and Ragnar Söderberg's Foundation; United States – Israel Binational Science Foundation (Grant 2011036), Umeå University; University Hospital of Regensburg; University of Groningen; University Medical Center Groningen; University of Michigan; University of Utrecht; Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) (b2011036); Velux Foundation; VU University’s Institute for Health and Care Research; Västra Götaland Foundation; Wellcome Trust (068545, 076113, 079895, 084723, 088869, WT064890, WT086596, WT098017, WT090532, WT098051, 098381); Wissenschaftsoffensive TMO; Yrjö Jahnsson Foundation; and Åke Wiberg Foundation. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute (NHLBI); the National Institutes of Health (NIH); or the U.S. Department of Health and Human Services.

Published
2017

4. Erratum to: A coherent approach for analysis of the Illumina HumanMethylation450 BeadChip improves data quality and performance in epigenome-wide association studies

Author

Benjamin Lehne, Alexander W. Drong, Marie Loh, Weihua Zhang, William R. Scott, Sian-Tsung Tan, Uzma Afzal, Reiner Schulz, James Scott, Marjo-Ritta Jarvelin, Paul Elliott, Mark I. McCarthy, Jaspal S. Kooner, and John C. Chambers

Subjects
Epigenomics, 0303 health sciences, 08 Information And Computing Sciences, Genome, Human, Bioinformatics, Quantitative Trait Loci, 0206 medical engineering, 05 Environmental Sciences, 02 engineering and technology, DNA Methylation, 06 Biological Sciences, Epigenesis, Genetic, 03 medical and health sciences, Humans, CpG Islands, Erratum, Software, 020602 bioinformatics, Genome-Wide Association Study, Oligonucleotide Array Sequence Analysis, 030304 developmental biology
Abstract

DNA methylation plays a fundamental role in the regulation of the genome, but the optimal strategy for analysis of genome-wide DNA methylation data remains to be determined. We developed a comprehensive analysis pipeline for epigenome-wide association studies (EWAS) using the Illumina Infinium HumanMethylation450 BeadChip, based on 2,687 individuals, with 36 samples measured in duplicate. We propose new approaches to quality control, data normalisation and batch correction through control-probe adjustment and establish a null hypothesis for EWAS using permutation testing. Our analysis pipeline outperforms existing approaches, enabling accurate identification of methylation quantitative trait loci for hypothesis driven follow-up experiments.

Published
2016

5. Investigation of Genetic Variation Underlying Central Obesity amongst South Asians

Author

William R, Scott, Weihua, Zhang, Marie, Loh, Sian-Tsung, Tan, Benjamin, Lehne, Uzma, Afzal, Juan, Peralta, Richa, Saxena, Sarju, Ralhan, Gurpreet S, Wander, Kiymet, Bozaoglu, Dharambir K, Sanghera, Paul, Elliott, James, Scott, John C, Chambers, and Jaspal S, Kooner

Subjects
Male, METABOLIC-SYNDROME, BLACK-AFRICAN, Physiology, lcsh:Medicine, LONGITUDINAL CHANGES, Mathematical and Statistical Techniques, Gene Frequency, Risk Factors, FOR-GESTATIONAL-AGE, Medicine and Health Sciences, Exome, lcsh:Science, DNA METHYLATION, INSULIN SENSITIVITY, Genomics, Middle Aged, Multidisciplinary Sciences, Physiological Parameters, CARDIOVASCULAR-DISEASE, Obesity, Abdominal, Physical Sciences, Science & Technology - Other Topics, Female, WAIST CIRCUMFERENCE, Statistics (Mathematics), Research Article, Statistical Distributions, Adult, Genotyping, Genotype, General Science & Technology, Research and Analysis Methods, Polymorphism, Single Nucleotide, White People, Asian People, MD Multidisciplinary, Genome-Wide Association Studies, Genetics, Humans, Obesity, Statistical Methods, Molecular Biology Techniques, Molecular Biology, Alleles, Aged, Evolutionary Biology, Science & Technology, Population Biology, Body Weight, lcsh:R, Genetic Variation, Biology and Life Sciences, Computational Biology, Human Genetics, FAT DISTRIBUTION, Sequence Analysis, DNA, Genome Analysis, Probability Theory, BIRTH-WEIGHT, Genetic Loci, lcsh:Q, Population Genetics, Mathematics, Genome-Wide Association Study, Meta-Analysis
Abstract

South Asians are 1/4 of the world’s population and have increased susceptibility to central obesity and related cardiometabolic disease. Knowledge of genetic variants affecting risk of central obesity is largely based on genome-wide association studies of common SNPs in Europeans. To evaluate the contribution of DNA sequence variation to the higher levels of central obesity (defined as waist hip ratio adjusted for body mass index, WHR) among South Asians compared to Europeans we carried out: i) a genome-wide association analysis of >6M genetic variants in 10,318 South Asians with focused analysis of population-specific SNPs; ii) an exome-wide association analysis of ~250K SNPs in protein-coding regions in 2,637 South Asians; iii) a comparison of risk allele frequencies and effect sizes of 48 known WHR SNPs in 12,240 South Asians compared to Europeans. In genome-wide analyses, we found no novel associations between common genetic variants and WHR in South Asians at P

Published
2016

6. Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

Author

Masato Isono, Jorma Viikari, Jianjun Liu, Xingwang Ye, Hao Peng, James Scott, Nanette R. Lee, Chris Hsu, Woon-Puay Koh, Torben Hansen, Vinicius Tragante, Christian Gieger, Tomohiro Katsuya, Aaron Isaacs, Norihiro Kato, Kjell Nikus, Dingliang Zhu, Tetsuro Miki, Zhirong Guo, Uzma Afzal, Hiroshi Kajio, Mika Kähönen, Terri L. Young, Jer-Yuarn Wu, Terho Lehtimäki, Oscar H. Franco, Niels Grarup, Stella Trompet, Rob M. van Dam, John Danesh, Weihua Zhang, Joanna D. Holbrook, Ryoichi Takayanagi, Miyako Kishimoto, Shuhei Yamaguchi, Jemma CHopewell, Thorkild I. A. Sørensen, André G. Uitterlinden, James Abbott, Cisca Wijmenga, Iris Postmus, Wilko Spiering, Gianluca Campanella, Michela Traglia, Ian J. Deary, Hirotsugu Ueshima, Tanja B. Grammer, Daniel OStram, Panos Deloukas, Huaixing Li, Tatsuaki Matsubara, Koichi Akiyama, Fumihiko Takeuchi, Young Jin Kim, Silke Szymczak, Dirk J. van Veldhuisen, Alexander W. Drong, Yu-Tang Gao, Imke Aits, Mark A. Pereira, Rajkumar Dorajoo, Marc Chadeau-Hyam, Benjamin Lehne, Bastiaan THeijman, Zuan Yu Mok, Timothy R. Braun, Mitsuhiro Yokota, Yechiel Friedlander, David C. Liewald, Pim van der Harst, Mahfuzar Rahman, Takayoshi Ohkubo, Aili Wang, Robert Clarke, Lisette Stolk, Pieter A. Doevendans, Wolfgang Lieb, Rebecca Mills, Sarah Parish, Katsuhiko Kohara, Martina Müller-Nurasyid, Nina Mononen, Steve Franks, Niek Verweij, Johanne Marie Justesen, Tin Aung, Rory Collins, J. Wouter Jukema, M.J. Pinidiyapathirage, Rory P. Wilson, Hong Kiat Ng, Joyce B. J. van Meurs, Yik Ying Teo, Wiek H. van Gilst, Wei Zheng, Robert WKoivula, John C. Chambers, Molly Scannell Bryan, Peng Chen, Gurpreet SWander, Lise Lotte N. Husemoen, David J. Stott, Li Ching Chang, Teresa Nutile, Lude Franke, Jaana Hartiala, Karen L. Mohlke, Folkert W. Asselbergs, Daniela Toniolo, Linda S. Adair, Tõnu Esko, Xueya Zhou, Marja Vääräsmäki, Ralhan Sarju, Hui Cai, Chiea Chuen Khor, Albert Hofman, Marc Jan Bonder, Shikta Das, Väinö Turjanmaa, Ying Wu, Masahiro Nakatochi, Habibul Ahsan, Michelle Ann Rozario, Andrew Bjonnes, Jaspal S. Kooner, Marcus E. Kleber, Rossella Sorice, Lavinia Paternoster, Yumi Matsushita, Tanika NKelly, Quang NNguyen, Stanley L. Hazen, Richa Saxena, Lin Tong, Kenneth Kwek, Keizo Ohnaka, Paolo Vineis, Sahoko Ichihara, Jos C. S. Kleinjans, Irene Mateo Leach, Yonghong Zhang, K. Sangher, Robin Young, Mika Kivimäki, Soterios A. Kyrtopoulos, Ching-Yu Cheng, William R. Scott, Andres Metspalu, Eranga N. Vithana, Ai Ling Teh, Tarunveer S. Ahluwalia, Alexandre F.R. Stewart, John M. Starr, Toru Nabika, Jeannette Lee, Andre Franke, Inês Barroso, Gail Davies, Olov Rolandsson, Wei Huang, Myron D. Gross, Yong-Bing Xiang, Cinzia Sala, Marjo-Riitta Järvelin, W. Frank Paul, Jian'an Luan, Jon White, Robert A. Scott, Torben Jørgensen, Jing He, Tien Yin Wong, Michiya Igase, Yi Zhang, Nur Sabrina Sapari, Simone Wahl, Ron T. Gansevoort, Rasheed Asif, Bruce H W Wolffenbuttel, Alauddin Ahmed, Annette Peters, Silva Kasela, Jiang He, Min Jin Go, Takao Sugiyama, Dongfeng Gu, Jagvir Grewal, Satoshi Umemura, Thomas Sparsø, Anna-Liisa Hartikainen, Hooman Allayee, Xu Wang, Meena Kumari, Eitaro Nakashima, Xu Lin, Harold Snieder, Ananda R. Wickremasinghe, Yun Kyoung Kim, Yuan-Tsong Chen, Chew-Kiat Heng, Alexessander Couto Alves, E. James Ames Hixso, Daniela Ruggiero, Kazuro Shimokawa, Muhammad GKibriya, Jong-Young Lee, Yasuharu Tabara, Oluf Pedersen, Bong Jo Kim, Marie Loh, Lili Milani, Loi D. Do, Dharambir Harambir, Joo Yeon Hwang, Thomas Meitinger, Todd L. Edwards, Danish Saleheen, Anuradhani Kasturiratne, Hiromi Rakugi, Sian Tsung Tan, Paul Elliott, Ken Yamamoto, Chien Hsiun Chen, Abbas Dehghan, Evelin Mihailov, Leo-Pekka Lyytikäinen, Xiao-Ou Shu, Richie Soong, Yiqin Wang, Marina Ciullo, Graciela E. Delgado, Olli TRaitakari, Jian-Min Yuan, Melanie Waldenberger, Jiemin Liao, E. Shyong Tai, Mark I. McCarthy, Winfried März, Nilesh J. Samani, Yap Seng Chong, Son TPham, Sarah E. Harris, Regina Courtney, Allan Linneberg, W.H. Wilson Tang, Epidemiology, Ophthalmology, Medical Microbiology & Infectious Diseases, Cardiology, Radiology & Nuclear Medicine, Internal Medicine, Erasmus MC other, Biochemie, Interne Geneeskunde, Toxicogenomics, RS: GROW - Oncology, RS: GROW - R1 - Prevention, Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), and Stem Cell Aging Leukemia and Lymphoma (SALL)

Subjects
Male, Vascular smooth muscle, Performance, Research Support, U.S. Gov't, P.H.S, Genome-wide association study, Blood Pressure, Expression, 030204 cardiovascular system & hematology, VARIANTS, P.H.S, genome-wide, 0302 clinical medicine, Risk Factors, Natriuretic Peptide, Brain, Disease, Non-U.S. Gov't, CENTRIC ARRAY, Genetics, Genetics & Heredity, Aged, 80 and over, 0303 health sciences, Research Support, Non-U.S. Gov't, 11 Medical And Health Sciences, Middle Aged, REGIONS, Phenotype, CpG site, Cardiovascular Diseases, CARDIOVASCULAR-DISEASE, DNA methylation, BIOS-consortium, Regression Analysis, Female, Life Sciences & Biomedicine, Adult, PULMONARY ARTERIAL-HYPERTENSION, Genotype, Population, Single-nucleotide polymorphism, Biology, Research Support, ta3111, Polymorphism, Single Nucleotide, White People, Article, N.I.H, 03 medical and health sciences, KIDNEY, Asian People, Research Support, N.I.H., Extramural, Journal Article, Humans, Genetic Predisposition to Disease, Gene, METAANALYSIS, 030304 developmental biology, Aged, Science & Technology, CARDIo GRAMplusCD, ta1184, Extramural, Genetic Variation, InterAct Consortium, 06 Biological Sciences, DNA Methylation, ta3121, Peptide Fragments, INDIVIDUALS, Blood pressure, Genetic Loci, TISSUE, RISK-FACTORS, U.S. Gov't, LifeLines Cohort Study, Developmental Biology, Genome-Wide Association Study
Abstract

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 x 10(-11) to 5.0 x 10(-21)). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 x 10(-6)). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.

Published
2015

7. New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

Author

Philippe Froguel, Pekka Jousilahti, Harry Campbell, Ellen M. Schmidt, Vasiliki Lagou, John Andrew Pospisilik, Ivana Kolcic, Igor Rudan, Mark A. Sarzynski, Brigitte Kühnel, Robin Haring, Paul Knekt, Christian Gieger, Eero Kajantie, Jian Yang, Tuomas O. Kilpeläinen, Hans L. Hillege, Niek Verweij, Sarah H Wild, Torben Hansen, Leena Taittonen, Michael Boehnke, Mark I. McCarthy, Joel N. Hirschhorn, Åsa K. Hedman, D. Timothy Bishop, James F. Wilson, Jian'an Luan, Leo-Pekka Lyytikäinen, Nita G. Forouhi, Mark Walker, Elodie Eury, Konstantin Strauch, Aroon D. Hingorani, Nam H. Cho, Peter Vollenweider, Erkki Vartiainen, Jong-Young Lee, Fredrik Karpe, Jiali Han, Joanne M. Jordan, Chen Lu, Henri Wallaschofski, Anna A. E. Vinkhuyzen, Alan R. Shuldiner, David J. Hunter, Mario Falchi, Aron S. Buchman, Caroline S. Fox, Robert A. Scott, Chan Soo Shin, Fernando Rivadeneira, Zari Dastani, Veikko Salomaa, Weihua Zhang, Rui Li, John C. Chambers, Thorkild I. A. Sørensen, André G. Uitterlinden, David A. Bennett, Marianna Sanna, Claire Bellis, Lars Bertram, Karl Michaëlsson, Yingchang Lu, Marie Loh, Loic Yengo, Bok-Ghee Han, Priya Srikanth, Laura Pascoe, Peter Wagner, Philip L. De Jager, Oscar H. Franco, Yongmei Liu, Stavroula Kanoni, Simone Gärtner, Ruth J. F. Loos, Eric E. Schadt, Claes Ohlsson, Cornelia M. van Duijn, Jorma S. A. Viikari, Stephan J. L. Bakker, Tamara B. Harris, Pirro G. Hysi, Samuli Ripatti, John R. B. Perry, Stefan A. Czerwinski, Tune H. Pers, Angela Döring, Ghazaleh Fatemifar, Tarunveer S. Ahluwalia, Liesbeth Vandenput, Carrie M. Nielson, Claudia Langenberg, Carolina Medina-Gomez, Mike A. Nalls, Erik Ingelsson, Barbara McKnight, Niels Grarup, L. Adrienne Cupples, Torben Jørgensen, Satu Männistö, Jianbo Na, Cristen J. Willer, Tuomo Rankinen, Irene Mateo Leach, Cecilia M. Lindgren, Marie-Claude Vohl, Ryan W. Walker, Yun Ju Sung, Joanne M. Murabito, Natasja M. van Schoor, Mika Kivimäki, Nicholas J. Wareham, Lei Yu, Markku Laakso, Julia A. Newton Bishop, Pim van der Harst, Qibin Qi, Veronique Bataille, Clive Osmond, Alan F. Wright, Audrey C. Choh, Charles C. White, Felix R. Day, Ron T. Gansevoort, Tiina Laatikainen, Ozren Polasek, Johan G. Eriksson, Mark M. Iles, Dena G. Hernandez, Meena Kumari, Dmitry Shungin, Jeffrey R. O'Connell, Joseph M. Zmuda, Antti Jula, Hyung Jin Choi, Albert Hofman, Steven R. Cummings, Youfang Liu, Vilmundur Gudnason, J. Brent Richards, Michael Stumvoll, Ayse Demirkan, Teresa Ferreira, Rosalie A. M. Dhonukshe-Rutten, Rahel Eckardt, Lude Franke, Karen L. Mohlke, Uzma Afzal, Kijoung Song, Till Ittermann, Janina S. Ried, Allan Linneberg, Nicholas D. Hastie, Laticia Oozageer, Johanna Kuusisto, John Blangero, Amélie Bonnefond, Panos Deloukas, Andrew P. Morris, Oluf Pedersen, Adam E. Locke, Emmi Tikkanen, Veronique Vitart, Aki S. Havulinna, Olli T. Raitakari, Inga Prokopenko, Peter Lichtner, Harm-Jan Westra, Katja Borodulin, Teemu Kuulasmaa, Lars Lind, Bradford Towne, Christine G. Lee, Mika Kähönen, Anke W. Enneman, Terrence S. Furey, Treva Rice, Abbas Dehghan, Jaspal S. Kooner, Dabeeru C. Rao, Terrence Forrester, Jing Hua Zhao, Xin Li, Mary F. Feitosa, Melissa E. Garcia, Tian Liu, Aarno Palotie, Eric S. Orwoll, Reedik Mägi, Daniel S. Evans, Elisabeth Widen, Tim D. Spector, Caroline Hayward, Annette Peters, Markku Heliövaara, Harald Grallert, Niina Eklund, Robert C. Kaplan, Ilja Demuth, Luigi Ferrucci, Kati Kristiansson, Amy Luke, Tõnu Esko, Ken K. Ong, Gregory J. Tranah, Angelo Tremblay, Ben A. Oostra, Stefan Gustafsson, Zhihong Zhu, Nina Smolej Narančić, Cameron D. Palmer, William R. Scott, Alexander Teumer, Anne U. Jackson, Markus Perola, Toshiko Tanaka, Lavinia Paternoster, Henry Völzke, Terho Lehtimäki, Dominik Spira, Karin M. A. Swart, Louis Pérusse, Matthias Blüher, Jari Lahti, M. Carola Zillikens, Kari E. North, Yvonne Boettcher, Douglas P. Kiel, Bamidele O. Tayo, Elisabeth Steinhagen-Thiessen, Diana L. Cousminer, Joanne E. Curran, Peter Kovacs, David M. Evans, Claude Bouchard, Alena Stančáková, Seppo Koskinen, Jack W. Kent, Alexander W. Drong, Massimo Mangino, Frédéric Fumeron, Richard S. Cooper, Juha Karjalainen, Nathalie van der Velde, Martin L. Buchkovich, Stéphane Lobbens, Cristina Menni, Anubha Mahajan, Nele Friedrich, Anke Tönjes, Colin A. McKenzie, Tom Forsén, Anne E. Justice, Lisette C. P. G. M. de Groot, Ingrid B. Borecki, Mingfeng Zhang, Tommy Cederholm, IOO, Internal medicine, Epidemiology and Data Science, EMGO - Musculoskeletal health, APH - Amsterdam Public Health, AMS - Amsterdam Movement Sciences, Geriatrics, Internal Medicine, Erasmus MC other, Epidemiology, Clinical Genetics, Institute for Molecular Medicine Finland, Clinicum, Department of General Practice and Primary Health Care, Behavioural Sciences, Samuli Olli Ripatti / Principal Investigator, Department of Public Health, Aarno Palotie / Principal Investigator, Johan Eriksson / Principal Investigator, Children's Hospital, Lastentautien yksikkö, University of Helsinki, Elisabeth Ingrid Maria Widen / Principal Investigator, Biostatistics Helsinki, Quantitative Genetics, Developmental Psychology Research Group, Complex Disease Genetics, Genomics of Neurological and Neuropsychiatric Disorders, Genomic Discoveries and Clinical Translation, Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Life Course Epidemiology (LCE), Cardiovascular Centre (CVC), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), and Stem Cell Aging Leukemia and Lymphoma (SALL)

Subjects
0301 basic medicine, Medicin och hälsovetenskap, Drosophila melanogaster/genetics, Nutrition and Disease, General Physics and Astronomy, Genome-wide association study, Medical and Health Sciences, Body fat percentage, Voeding en Ziekte, CUTANEOUS NEVI, Mass index, Human Nutrition & Health, Adiposity, INSULIN-RESISTANCE, Multidisciplinary, body fat, cardiometabolic traits, genome-wide association study, meta-analysis, biology, Disease genetics, Leptin, Humane Voeding & Gezondheid, COMMON VARIANTS, Public Health, Global Health, Social Medicine and Epidemiology, 3. Good health, Biological sciences, Cardiovascular diseases, Drosophila melanogaster, Gene Knockdown Techniques, ENERGY-BALANCE, Medical Genetics, medicine.medical_specialty, SUSCEPTIBILITY LOCI, Heart Diseases, 515 Psychology, Science, Quantitative Trait Loci, PROVIDES INSIGHTS, Quantitative trait locus, General Biochemistry, Genetics and Molecular Biology, Article, GENETIC ARCHITECTURE, 03 medical and health sciences, MASS INDEX, Insulin resistance, Internal medicine, MD Multidisciplinary, Genetics, medicine, Life Science, Animals, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Medicinsk genetik, VLAG, Global Nutrition, Wereldvoeding, Gene Expression Regulation/physiology, C-reactive protein, Metabolic diseases, General Chemistry, ta3121, medicine.disease, Onderwijsinstituut, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Adiposity/genetics, Drosophila melanogaster/metabolism, Genome-Wide Association Study, Heart Diseases/genetics, Quantitative Trait Loci/genetics, 030104 developmental biology, Endocrinology, Gene Expression Regulation, 3121 General medicine, internal medicine and other clinical medicine, biology.protein, Lean body mass, IDENTIFIES COMMON
Abstract

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P, A genome-wide association meta-analysis study here shows novel genetic loci to be associated to body fat percentage, and describes cross-phenotype association that further demonstrate a close relationship between adiposity and cardiovascular disease risk.

Published
2015

8. A coherent approach for analysis of the Illumina HumanMethylation450 BeadChip improves data quality and performance in epigenome-wide association studies

Author

James Scott, Weihua Zhang, Alexander W. Drong, Sian-Tsung Tan, Jaspal S. Kooner, William R. Scott, Marjo-Riitta Järvelin, Uzma Afzal, Paul Elliott, John C. Chambers, Marie Loh, Benjamin Lehne, Mark I. McCarthy, Medical Research Council (MRC), National Institute for Health Research, Imperial College Healthcare NHS Trust- BRC Funding, Action on Hearing Loss, Wellcome Trust, and British Heart Foundation

Subjects
Epigenomics, PIPELINE, Bioinformatics, Quantitative Trait Loci, 05 Environmental Sciences, Method, Genome-wide association study, Computational biology, QUANTILE NORMALIZATION, SUBSET-QUANTILE, Quantitative trait locus, Biology, PERIPHERAL-BLOOD, METHYLATION ARRAY DATA, Epigenesis, Genetic, MICROARRAY, Humans, DNA METHYLATION, Quantile normalization, GENE-EXPRESSION, Oligonucleotide Array Sequence Analysis, Genetics, Genetics & Heredity, Science & Technology, Genome, Human, Epigenome, PANCREATIC-ISLETS, 06 Biological Sciences, CANCER, Biotechnology & Applied Microbiology, Data quality, DNA methylation, ARRAY, Human genome, CpG Islands, 08 Information and Computing Sciences, Life Sciences & Biomedicine, Software, Genome-Wide Association Study
Abstract

DNA methylation plays a fundamental role in the regulation of the genome, but the optimal strategy for analysis of genome-wide DNA methylation data remains to be determined. We developed a comprehensive analysis pipeline for epigenome-wide association studies (EWAS) using the Illumina Infinium HumanMethylation450 BeadChip, based on 2,687 individuals, with 36 samples measured in duplicate. We propose new approaches to quality control, data normalisation and batch correction through control-probe adjustment and establish a null hypothesis for EWAS using permutation testing. Our analysis pipeline outperforms existing approaches, enabling accurate identification of methylation quantitative trait loci for hypothesis driven follow-up experiments. Electronic supplementary material The online version of this article (doi:10.1186/s13059-015-0600-x) contains supplementary material, which is available to authorized users.

Published
2015

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