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14 results on '"John Danesh"'

1. Quality control and removal of technical variation of NMR metabolic biomarker data in ~120,000 UK Biobank participants

Author

Scott C. Ritchie, Praveen Surendran, Savita Karthikeyan, Samuel A. Lambert, Thomas Bolton, Lisa Pennells, John Danesh, Emanuele Di Angelantonio, Adam S. Butterworth, Michael Inouye, Ritchie, Scott C [0000-0002-8454-9548], Butterworth, Adam S [0000-0002-6915-9015], and Apollo - University of Cambridge Repository

Subjects
Statistics and Probability, Quality Control, Magnetic Resonance Spectroscopy, Humans, Library and Information Sciences, Statistics, Probability and Uncertainty, Magnetic Resonance Imaging, United Kingdom, Computer Science Applications, Education, Information Systems, Biological Specimen Banks
Abstract

Funder: S.C.R was funded by the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre (BRC) (BRC-1215-20014) and by the British Heart Foundation (BHF) programme grant (RG/18/13/33946)., Funder: Praveen Surendran was supported by a Rutherford Fund Fellowship from the Medical Research Council grant MR/S003746/1, Funder: Savita Karthikeyan was funded by a British Heart Foundation Programme Grant (RG/18/13/33946), Funder: Samuel A. Lambert was supported by a Canadian Institutes of Health Research postdoctoral fellowship (MFE-171279), Funder: Thomas Bolton was funded by the NIHR Blood and Transplant Research Unit in Donor Health and Genomics (NIHR BTRU-2014-10024), Funder: Lisa Pennells was funded by a British Heart Foundation Programme Grant (RG/18/13/33946), Funder: John Danesh holds a British Heart Foundation Professorship and a NIHR Senior Investigator Award., Funder: Michael Inouye is supported by the Munz Chair of Cardiovascular Prediction and Prevention and the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014), and was also supported by the UK Economic and Social Research 878 Council (ES/T013192/1)., Metabolic biomarker data quantified by nuclear magnetic resonance (NMR) spectroscopy in approximately 121,000 UK Biobank participants has recently been released as a community resource, comprising absolute concentrations and ratios of 249 circulating metabolites, lipids, and lipoprotein sub-fractions. Here we identify and characterise additional sources of unwanted technical variation influencing individual biomarkers in the data available to download from UK Biobank. These included sample preparation time, shipping plate well, spectrometer batch effects, drift over time within spectrometer, and outlier shipping plates. We developed a procedure for removing this unwanted technical variation, and demonstrate that it increases signal for genetic and epidemiological studies of the NMR metabolic biomarker data in UK Biobank. We subsequently developed an R package, ukbnmr, which we make available to the wider research community to enhance the utility of the UK Biobank NMR metabolic biomarker data and to facilitate rapid analysis.

Published
2023

2. The Polygenic Score Catalog as an open database for reproducibility and systematic evaluation

Author

Aoife McMahon, Helen Parkinson, Simon Jupp, Laurent Gil, Scott C. Ritchie, Samuel A. Lambert, Jacqueline A. L. MacArthur, Michael Inouye, Yu Xu, Annalisa Buniello, John Danesh, Gad Abraham, and Michael A Chapman

Subjects
Metadata, 0303 health sciences, 03 medical and health sciences, 0302 clinical medicine, Information retrieval, Extramural, Genetics, MEDLINE, Biology, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

We present the Polygenic Score (PGS) Catalog ( https://www.PGSCatalog.org ), an open resource of published scores (including variants, alleles and weights) and consistently curated metadata required for reproducibility and independent applications. The PGS Catalog has capabilities for user deposition, expert curation and programmatic access, thus providing the community with a platform for PGS dissemination, research and translation.

Published
2021

3. A cross-platform approach identifies genetic regulators of human metabolism and health

Author

Kay-Tee Khaw, Angela M. Wood, Julian L. Griffin, Gabi Kastenmüller, Fiona M. Gribble, Adam S. Butterworth, Luca A. Lotta, Verena Zuber, Chen Li, Victoria P W Auyeung, Johannes Raffler, Isobel D. Stewart, Nita G. Forouhi, Jian'an Luan, Nicholas J. Wareham, Claudia Langenberg, Maik Pietzner, Laura B. L. Wittemans, Eleanor Wheeler, Robert A. Scott, Roberto Bonelli, John Danesh, Frank Reimann, Praveen Surendran, Stephen Burgess, Ellie Paige, Clare Oliver-Williams, Albert Koulman, Fumiaki Imamura, Eric B. Fauman, Gregory A. Michelotti, Melanie Bahlo, Eleanor Sanderson, and Emma K. Biggs

Subjects
Nonsynonymous substitution, 0303 health sciences, Mechanism (biology), Genome-wide association study, Computational biology, Biology, 03 medical and health sciences, 0302 clinical medicine, Pleiotropy, Mendelian randomization, Genetics, Genetic Pleiotropy, Metabolome, Allelic heterogeneity, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

In cross-platform analyses of 174 metabolites, we identify 499 associations (P

Published
2021

4. Integrative analysis of the plasma proteome and polygenic risk of cardiometabolic diseases

Author

Petar Scepanovic, Jonathan Marten, Shu Mei Teo, Michael Inouye, Nicholas A. Watkins, David J. Roberts, Scott C. Ritchie, Brian G. Drew, Nicole Soranzo, Adam S. Butterworth, Matthew Arnold, Sol Lim, Samuel A. Lambert, Michael A Chapman, Yingying Liu, Amit Khera, Emanuele Di Angelantonio, Sohail Zahid, Stephen Burgess, Mark Chaffin, John Danesh, Anna C. Calkin, Willem H. Ouwehand, Sekar Kathiresan, Gad Abraham, Ritchie, Scott C [0000-0002-8454-9548], Lambert, Samuel A [0000-0001-8222-008X], Arnold, Matthew [0000-0001-6339-1115], Lim, Sol [0000-0001-7786-3355], Chaffin, Mark [0000-0002-1234-5562], Ouwehand, Willem H [0000-0002-7744-1790], Drew, Brian G [0000-0002-7839-9467], Calkin, Anna C [0000-0002-9861-0602], Soranzo, Nicole [0000-0003-1095-3852], Burgess, Stephen [0000-0001-5365-8760], Chapman, Michael [0000-0002-4582-6303], Kathiresan, Sekar [0000-0002-3711-7101], Butterworth, Adam S [0000-0002-6915-9015], Inouye, Michael [0000-0001-9413-6520], and Apollo - University of Cambridge Repository

Subjects
Adult, Male, Multifactorial Inheritance, Letter, Heart Diseases, Proteome, Population genetics, Endocrinology, Diabetes and Metabolism, Disease, Type 2 diabetes, Quantitative trait locus, Bioinformatics, Coronary artery disease, Pathogenesis, Young Adult, Metabolic Diseases, Physiology (medical), Internal Medicine, Genetic predisposition, Medicine, Humans, Genetic Predisposition to Disease, Public Health Surveillance, Vascular diseases, business.industry, Disease Management, Functional genomics, Cell Biology, Blood Proteins, Middle Aged, medicine.disease, Metabolism, England, Female, Disease Susceptibility, business, Biomarkers, Kidney disease
Abstract

Cardiometabolic diseases are frequently polygenic in architecture, comprising a large number of risk alleles with small effects spread across the genome1–3. Polygenic scores (PGS) aggregate these into a metric representing an individual’s genetic predisposition to disease. PGS have shown promise for early risk prediction4–7 and there is an open question as to whether PGS can also be used to understand disease biology8. Here, we demonstrate that cardiometabolic disease PGS can be used to elucidate the proteins underlying disease pathogenesis. In 3,087 healthy individuals, we found that PGS for coronary artery disease, type 2 diabetes, chronic kidney disease and ischaemic stroke are associated with the levels of 49 plasma proteins. Associations were polygenic in architecture, largely independent of cis and trans protein quantitative trait loci and present for proteins without quantitative trait loci. Over a follow-up of 7.7 years, 28 of these proteins associated with future myocardial infarction or type 2 diabetes events, 16 of which were mediators between polygenic risk and incident disease. Twelve of these were druggable targets with therapeutic potential. Our results demonstrate the potential for PGS to uncover causal disease biology and targets with therapeutic potential, including those that may be missed by approaches utilizing information at a single locus., Ritchie et al. use polygenic scores to identify plasma proteins with causal roles in cardiometabolic disease.

Published
2021

5. Genome-wide analysis of blood lipid metabolites in over 5000 South Asians reveals biological insights at cardiometabolic disease loci

Author

Zoubia Hina, Julian L. Griffin, Asif Rasheed, Nadeem Qamar, Danish Saleheen, Dirk S. Paul, Imran Saleem, Taniya Sattar, M. Ishaq, Nadeem Hayat Mallick, Adam S. Butterworth, Philippe M. Frossard, Daniel Ziemek, Fazal-ur-Rehman Memon, Syed Nadeem Hasan Rizvi, Albert Koulman, Anjum Jalal, Tahir Saghir, John Danesh, Angela M. Wood, David Stacey, Eric B. Fauman, Unzila Ishtiaq, Anis Memon, Rachel M. Y. Ong, Eric L. Harshfield, Shahid Abbas, Zameer-ul-Asar, Zia Yaqub, Syed Zahed Rasheed, Harshfield, Eric [0000-0001-8767-0928], Paul, Dirk [0000-0002-8230-0116], Danesh, John [0000-0003-1158-6791], Butterworth, Adam [0000-0002-6915-9015], Wood, Angela [0000-0002-7937-304X], Koulman, Albert [0000-0001-9998-051X], Apollo - University of Cambridge Repository, and Paul, Dirk S [0000-0002-8230-0116]

Subjects
South asia, Population, Myocardial Infarction, Blood lipids, Disease, Gaussian Graphical Modelling, Polymorphism, Single Nucleotide, White People, 03 medical and health sciences, 0302 clinical medicine, Asian People, Lipidomics, Genetics, Medicine, South Asian, Humans, Genetic Predisposition to Disease, education, Gene, 030304 developmental biology, 0303 health sciences, education.field_of_study, business.industry, General Medicine, Lipidome, Lipids, Genetic architecture, 3. Good health, Network analysis, business, 030217 neurology & neurosurgery, Research Article, Genome-Wide Association Study
Abstract

Background Genetic, lifestyle, and environmental factors can lead to perturbations in circulating lipid levels and increase the risk of cardiovascular and metabolic diseases. However, how changes in individual lipid species contribute to disease risk is often unclear. Moreover, little is known about the role of lipids on cardiovascular disease in Pakistan, a population historically underrepresented in cardiovascular studies. Methods We characterised the genetic architecture of the human blood lipidome in 5662 hospital controls from the Pakistan Risk of Myocardial Infarction Study (PROMIS) and 13,814 healthy British blood donors from the INTERVAL study. We applied a candidate causal gene prioritisation tool to link the genetic variants associated with each lipid to the most likely causal genes, and Gaussian Graphical Modelling network analysis to identify and illustrate relationships between lipids and genetic loci. Results We identified 253 genetic associations with 181 lipids measured using direct infusion high-resolution mass spectrometry in PROMIS, and 502 genetic associations with 244 lipids in INTERVAL. Our analyses revealed new biological insights at genetic loci associated with cardiometabolic diseases, including novel lipid associations at the LPL, MBOAT7, LIPC, APOE-C1-C2-C4, SGPP1, and SPTLC3 loci. Conclusions Our findings, generated using a distinctive lipidomics platform in an understudied South Asian population, strengthen and expand the knowledge base of the genetic determinants of lipids and their association with cardiometabolic disease-related loci.

Published
2021

6. Improving reporting standards for polygenic scores in risk prediction studies

Author

Cecelia P. Tamburro, Robert A. Hegele, Catherine Sillari, Nilanjan Chatterjee, Jack W. O’Sullivan, A. Cecile J.W. Janssens, Kelly E. Ormond, Megan C. Roberts, Robb Rowley, Samuel A. Lambert, Jacqueline S. Dron, Muin J. Khoury, Jacqueline Al MacArthur, Mark I McCarthy, Douglas F. Easton, Charles Kooperberg, Deanna Brockman, Antonis C. Antoniou, Hannah Wand, Karen Edwards, Katrina A.B. Goddard, Kim Kinnear, John Danesh, Iftikhar J. Kullo, Genevieve L. Wojcik, Erin M. Ramos, Eric Venner, Michael A. Iacocca, Peter Kraft, Michael Inouye, Amit Khera, Helen Parkinson, Katherine Vlessis, Lambert, Samuel A [0000-0001-8222-008X], Kullo, Iftikhar J [0000-0002-6524-3471], Dron, Jacqueline S [0000-0002-3045-6530], McCarthy, Mark I [0000-0002-4393-0510], Easton, Douglas F [0000-0003-2444-3247], Khera, Amit V [0000-0001-6535-5839], Ormond, Kelly E [0000-0002-1033-0818], Kraft, Peter [0000-0002-4472-8103], MacArthur, Jaqueline AL [0000-0002-3550-9769], Inouye, Michael [0000-0001-9413-6520], Wojcik, Genevieve L [0000-0001-7206-8088], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, medicine.medical_specialty, Multifactorial Inheritance, General Science & Technology, Computer science, Best practice, Genetics, Medical, MEDLINE, Risk Assessment, Article, Field (computer science), 03 medical and health sciences, 0302 clinical medicine, Resource (project management), Medical, Genetics, medicine, Humans, Genetic Predisposition to Disease, health care economics and organizations, Estimation, Multidisciplinary, Prevention, Human Genome, Reproducibility of Results, Benchmarking, Data science, Good Health and Well Being, 030104 developmental biology, 030220 oncology & carcinogenesis, Transparency (graphic), Medical genetics
Abstract

Polygenic risk scores (PRSs), which often aggregate results from genome-wide association studies, can bridge the gap between initial discovery efforts and clinical applications for the estimation of disease risk using genetics. However, there is notable heterogeneity in the application and reporting of these risk scores, which hinders the translation of PRSs into clinical care. Here, in a collaboration between the Clinical Genome Resource (ClinGen) Complex Disease Working Group and the Polygenic Score (PGS) Catalog, we present the Polygenic Risk Score Reporting Standards (PRS-RS), in which we update the Genetic Risk Prediction Studies (GRIPS) Statement to reflect the present state of the field. Drawing on the input of experts in epidemiology, statistics, disease-specific applications, implementation and policy, this comprehensive reporting framework defines the minimal information that is needed to interpret and evaluate PRSs, especially with respect to downstream clinical applications. Items span detailed descriptions of study populations, statistical methods for the development and validation of PRSs and considerations for the potential limitations of these scores. In addition, we emphasize the need for data availability and transparency, and we encourage researchers to deposit and share PRSs through the PGS Catalog to facilitate reproducibility and comparative benchmarking. By providing these criteria in a structured format that builds on existing standards and ontologies, the use of this framework in publishing PRSs will facilitate translation into clinical care and progress towards defining best practice.

Published
2020
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7. Author Correction: Genomic risk score offers predictive performance comparable to clinical risk factors for ischaemic stroke

Author

Tingting Wang, Rainer Malik, Agus Salim, Ekaterina Yonova-Doing, Martin Dichgans, Michael Inouye, John Danesh, Gad Abraham, Adam S. Butterworth, and Joanna M. M. Howson

Subjects
medicine.medical_specialty, Multidisciplinary, Framingham Risk Score, business.industry, Science, General Physics and Astronomy, Genome-wide association study, General Chemistry, medicine.disease, General Biochemistry, Genetics and Molecular Biology, Internal medicine, Ischaemic stroke, medicine, lcsh:Q, ddc:500, Personalized medicine, lcsh:Science, business, Clinical risk factor, Stroke
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020

8. Assessing the causal association of glycine with risk of cardio-metabolic diseases

Author

Heribert Schunkert, Stephen Burgess, Adam S. Butterworth, Nita G. Forouhi, Julian L. Griffin, Claudia Langenberg, Savita Karthikeyan, Clare Oliver-Williams, Lingyao Zeng, Laura B. L. Wittemans, Felix R. Day, Albert Koulman, Isobel D. Stewart, Angela M. Wood, Kay-Tee Khaw, Luca A. Lotta, Nicholas J. Wareham, John Danesh, Praveen Surendran, Jeanette Erdmann, Joanna M. M. Howson, Robert A. Scott, Fumiaki Imamura, Day, Felix R [0000-0003-3789-7651], Koulman, Albert [0000-0001-9998-051X], Imamura, Fumiaki [0000-0002-6841-8396], Forouhi, Nita G [0000-0002-5041-248X], Burgess, Stephen [0000-0001-5365-8760], Howson, Joanna MM [0000-0001-7618-0050], Butterworth, Adam S [0000-0002-6915-9015], Langenberg, Claudia [0000-0002-5017-7344], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Science, Glycine, General Physics and Astronomy, Genome-wide association study, Coronary Disease, 02 engineering and technology, Type 2 diabetes, Bioinformatics, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Insulin resistance, Polymorphism (computer science), Diabetes mellitus, Hyperinsulinism, medicine, Humans, Genetic Predisposition to Disease, lcsh:Science, Genetic association, Multidisciplinary, business.industry, Incidence, General Chemistry, 021001 nanoscience & nanotechnology, medicine.disease, 3. Good health, ddc, 030104 developmental biology, Diabetes Mellitus, Type 2, Genetic Loci, Meta-analysis, lcsh:Q, 0210 nano-technology, business, Metabolic Networks and Pathways, Genome-Wide Association Study
Abstract

Circulating levels of glycine have previously been associated with lower incidence of coronary heart disease (CHD) and type 2 diabetes (T2D) but it remains uncertain if glycine plays an aetiological role. We present a meta-analysis of genome-wide association studies for glycine in 80,003 participants and investigate the causality and potential mechanisms of the association between glycine and cardio-metabolic diseases using genetic approaches. We identify 27 genetic loci, of which 22 have not previously been reported for glycine. We show that glycine is genetically associated with lower CHD risk and find that this may be partly driven by blood pressure. Evidence for a genetic association of glycine with T2D is weaker, but we find a strong inverse genetic effect of hyperinsulinaemia on glycine. Our findings strengthen evidence for a protective effect of glycine on CHD and show that the glycine-T2D association may be driven by a glycine-lowering effect of insulin resistance., Epidemiological studies have associated circulating levels of the amino acid glycine with cardiometabolic outcomes. Here, in a genome-wide meta-analysis of 80,003 individuals, Wittemans et al. identify 22 novel genetic loci for glycine and find a causal relationship with coronary heart disease using MR.

Published
2019

9. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility

Author

Tazeen H. Jafar, Lars Lind, Peter Almgren, Wendy Winckler, Eitaro Nakashima, Young Min Cho, Annette Peters, Rona J. Strawbridge, Ananda R. Wickremasinghe, Katharine R. Owen, Lee-Ming Chuang, Tien-Jyun Chang, Graeme I. Bell, James B. Meigs, Bill Musk, Timo A. Lakka, Elin Grundberg, Wei Lu, Sarah Edkins, George Dedoussis, Weiping Jia, Danish Saleheen, Suthesh Sivapalaratnam, Maria Samuel, Tien Yin Wong, Lu Qi, Pierre Fontanillas, Momoko Horikoshi, Jirong Long, Abdul Basit, Anubha Mahajan, Andrew T. Hattersley, Markus M. Nöthen, Denis Rybin, Inger Njølstad, S. Krithika, Miguel Cruz, Delilah Zabaneh, Leena Peltonen, Jasmina Kravic, Sangsoo Kim, David Couper, Lori L. Bonnycastle, Heather M. Stringham, Yi-Cheng Chang, Paul Elliott, Eric J.G. Sijbrands, Nita G. Forouhi, Alena Stančáková, Ghazala Mirza, Robert W. Lawrence, Ruth J. F. Loos, Norman Klopp, Shiro Maeda, Martina Müller-Nurasyid, Jer-Yuarn Wu, Jianjun Liu, Kee Seng Chia, Elodie Eury, Loukianos S. Rallidis, Timothy M. Frayling, Ken Yamamoto, David Altshuler, Gunnar Sigurosson, Harald Grallert, Jackie F. Price, Barbara Thorand, Jouko Saramies, Malene M. Kristensen, Sonali Pechlivanis, Inês Barroso, Jong-Young Lee, Melissa Parkin, Josée Dupuis, Stéphane Lobbens, Jesús Kumate, Elena Tremoli, Sudhir Kowlessur, Xueling Sim, Norihiro Kato, Philippe Froguel, Kathleen Stirrups, Eero Lindholm, Alex S. F. Doney, Andres Metspalu, Yu-Tang Gao, Roman Wennauer, Xiao-Ou Shu, Marilyn C. Cornelis, Veikko Salomaa, Nanette R. Lee, Johanna Kuusisto, Caroline S. Fox, Man Li, James Scott, Wing-Yee So, Andrew R. Wood, Inga Prokopenko, Oddgeir L. Holmen, Tin Aung, Ryoichi Takayanagi, Chen Suo, Hara Kazuo, Carl G. P. Platou, Ann M. Kelly, Teresa Ferreira, Karl-Heinz Jöckel, Wei-Yen Lim, James F. Wilson, Tom Forsén, Qi Sun, Valur Emilsson, Gonçalo R. Abecasis, Fan Zhang, Timo Saaristo, Harry Campbell, Ying Wu, Mark Seielstad, Wei Zheng, Han Chen, Stavroula Kanoni, Yuqian Bao, Jose C. Florez, Wan Ting Tay, Ronald C. WMa, Gerald Steinbach, Min Jin Go, Rong Zhang, Junbin Liang, Vasiliki Lagou, Leif Groop, Emil Rehnberg, Nabi Shah, Weihua Zhang, Yun Li, Bengt Sennblad, Olle Melander, Nancy L. Pedersen, Muhammed Islam, Jaakko Tuomilehto, Young Jin Kim, Richard N. Bergman, Juliana C.N. Chan, Eleftheria Zeggini, Andrew D. Johnson, Kees Hovingh, Joban Sehmi, Rainer Rauramaa, Satu Männistö, Reedik Mägi, Samuel Liju, Mingyu Yang, Ayellet V. Segrè, Noël P. Burtt, Mozhgan Dorkhan, Beverley Balkau, Neelam Hassanali, Hyun Min Kang, Fabrizio Veglia, Eeva Korpi-Hyövälti, Loic Yengo, Elizabeth J. Rossin, Angela Silveira, Maggie C.Y. Ng, Yuan-Tsong Chen, Anders Hamsten, David R. Matthews, Mark J. Caulfield, Emmi Tikkanen, Tanya M. Teslovich, John R. B. Perry, Karen L. Mohlke, Sarah E. Hunt, Soo Heon Kwak, Jorge Escobedo, Christopher J. Groves, Ulf de Faire, Jeremy B M Jowett, Gudmar Thorleifsson, Michael Roden, Evelin Mihailov, Viswanathan Mohan, Craig L. Hanis, Thomas WMühleisen, Congrong Wang, Sonia Shah, Kyle J. Gaulton, Jaspal S. Kooner, Jiro Nakamura, Mustafa Atalay, Linda S. Adair, S Wiltshire, Tõnu Esko, Anna Jonsson, Antigone S. Dimas, Karin Leander, Li Ching Chang, George B. Grant, Bo Isomaa, Anne U. Jackson, Claudia Langenberg, Kristian Hveem, Yoon Shin Cho, Astradur B. Hreidarsson, Xu Wang, Keizo Ohnaka, Alexandra C. Nica, Simon D. Rees, Pau Navarro, Sekar Kathiresan, Rob M. van Dam, Zafar I. Hydrie, Bok Ghee Han, Francis S. Collins, Fuu Jen Tsai, Unnur Thorsteinsdottir, Ross M. Fraser, Caroline Hayward, Cornelia M. van Duijn, Samuli Ripatti, Mieke D. Trip, Hyung Lae Kim, Rafn Benediktsson, Candace Guiducci, Bruna Gigante, Kyong Soo Park, Wen Hong L. Kao, Tom Wilsgaard, Leena Kinnunen, John Danesh, Alan James, Alan R. Shuldiner, Mitsuhiro Yokota, Jen Mai Lee, Kari Stefansson, Erik Ingelsson, Colin N. A. Palmer, David J. Hunter, Paul Zimmet, Manickam Chidambaram, Sirkka Keinänen-Kiukaanniemi, Laura J. Scott, Susanne Moebus, Benjamin F. Voight, Wolfgang Rathmann, Hassan Khan, Thomas Illig, Prasad Katulanda, Christian Gieger, Andrew D. Morris, Yik Ying Teo, Andrew P. Morris, Venkatesan Radha, N. William Rayner, Johan G. Eriksson, Christian Dina, Igor Rudan, Sailaja Vedantam, Cheng Hu, James S. Pankow, Ann-Christine Syvänen, Karl Gertow, Valeriya Lyssenko, Guillaume Charpentier, Albert Hofman, Chiea Chuen Khor, Joseph Trakalo, Peter Kraft, Takashi Kadowaki, Qiuyin Cai, John C. Chambers, André G. Uitterlinden, Simon C. Potter, Nicholas J. Wareham, Soumya Raychaudhuri, Jian'an Luan, Tiinamaija Tuomi, Anthony H. Barnett, Juha Saltevo, Robert A. Scott, Valgerdur Steinthorsdottir, Peng Keat Ng, Mark I. McCarthy, Åsa K. Hedman, Kerrin S. Small, Julia Meyer, Frank B. Hu, Cecilia M. Lindgren, Jennifer E. Below, Nancy J. Cox, Jennie Hui, Andrew Crenshaw, Latonya F. Been, Nam H. Cho, Janani Pinidiyapathirage, A. Samad Shera, Bernhard OBoehm, Jason Carey, Augustine Kong, Twee Hee Ong, Philippe M. Frossard, Donald W. Bowden, Toshimasa Yamauchi, Steve E. Humphries, Cordelia Langford, Xinzhong Li, Hiroshi Ikegami, Stéphane Cauchi, Ching-Ti Liu, Michael Boehnke, Peter M. Nilsson, Debashish Das, John Beilby, Robin Young, Christian Herder, Asif Rasheed, Neil Robertson, Raimund Erbel, Fumihiko Takeuchi, Markku Laakso, Esteban J. Parra, Panos Deloukas, Eric Boerwinkle, Adan Valladares-Salgado, Chien-Hsiun Chen, Kay-Tee Khaw, Damiano Baldassarre, Ashok Kumar, E. Shyong Tai, Peter S. Chines, Dharambir KSanghera, Peter Donnelly, [ 1 ] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England [ 2 ] Natl Inst Hlth, Ctr Genome Sci, Gangoe Myeon, Yeonje Ri, South Korea [ 3 ] Univ London Imperial Coll Sci Technol & Med, London, England [ 4 ] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA [ 5 ] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX1 2JD, England [ 6 ] NHLBI, Framingham Heart Study, Framingham, MA USA [ 7 ] Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA [ 8 ] Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA [ 9 ] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London, England [ 10 ] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England [ 11 ] Ctr Noncommunicable Dis Pakistan, Karachi, Pakistan [ 12 ] Natl Univ Singapore, Dept Epidemiol & Publ Hlth, Singapore 117548, Singapore [ 13 ] Wellcome Trust Sanger Inst, Cambridge, England [ 14 ] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA [ 15 ] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA [ 16 ] Lund Univ, Scania Univ Hosp, Dept Clin Sci Malmo, Ctr Diabet, Malmo, Sweden [ 17 ] Univ Eastern Finland, Inst Biomed, Kuopio, Finland [ 18 ] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore [ 19 ] Natl Univ Singapore, Dept Ophthalmol, Singapore 117548, Singapore [ 20 ] IRCCS, Ctr Cardiol Monzino, Milan, Italy [ 21 ] Univ Milan, Dept Pharmacol Sci, Milan, Italy [ 22 ] INSERM, Ctr Rech Epidemiol & Sante Populat CESP, U1018, Villejuif, France [ 23 ] Univ Paris 11, UMRS 1018, Villejuif, France [ 24 ] Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Endocrinol & Metab, Shanghai Key Lab Diabet Mellitus,Shanghai Diabet, Shanghai 200030, Peoples R China [ 25 ] Univ Birmingham, Coll Med & Dent Sci, Birmingham, W Midlands, England [ 26 ] Heart England Natl Hlth Serv NHS Fdn Trust, Ctr Biomed Res, Birmingham, W Midlands, England [ 27 ] Univ Cambridge, Addenbrookes Hosp, Metab Res Labs, Inst Metab Sci, Cambridge CB2 2QQ, England [ 28 ] Addenbrookes Hosp, Inst Metab Sci, Cambridge Biomed Res Ctr, Natl Inst Hlth Res, Cambridge, England [ 29 ] Baqai Inst Diabetol & Endocrinol, Karachi, Pakistan [ 30 ] Univ Oklahoma, Hlth Sci Ctr, Coll Med, Dept Pediat,Sect Genet, Oklahoma City, OK 73190 USA [ 31 ] Sir Charles Gairdner Hosp, Busselton Populat Med Res Inst, Nedlands, WA 6009, Australia [ 32 ] Queen Elizabeth II Med Ctr, PathWest Lab Med Western Australia, Nedlands, WA, Australia [ 33 ] Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia [ 34 ] Univ Chicago, Dept Med, Chicago, IL 60637 USA [ 35 ] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA [ 36 ] Univ Iceland, Fac Med, Reykjavik, Iceland [ 37 ] Landspitali Univ Hosp, Reykjavik, Iceland [ 38 ] Cedars Sinai Med Ctr, Diabet & Obes Res Inst, Los Angeles, CA 90048 USA [ 39 ] Univ Med Ctr Ulm, Div Endocrinol & Diabet, Dept Internal Med, Ulm, Germany [ 40 ] Nanyang Technol Univ, Lee Kong Chian LKC Sch Med, Singapore 639798, Singapore [ 41 ] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA [ 42 ] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA [ 43 ] NHGRI, NIH, Bethesda, MD 20892 USA [ 44 ] Broad Inst Harvard & Massachusetts Inst Technol M, Cambridge, MA USA [ 45 ] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Vanderbilt Epidemiol Ctr,Dept Med, Nashville, TN 37212 USA [ 46 ] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland [ 47 ] Univ Edinburgh, Western Gen Hosp, MRC, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland [ 48 ] CNRS, Unite Mixte Rech UMR 8199, Inst Biol, Lille, France [ 49 ] Univ Lille 2, Inst Pasteur, Lille, France [ 50 ] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, London, England [ 51 ] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, Barts & London Genome Ctr, London, England [ 52 ] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & 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Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA [ 95 ] Addenbrookes Hosp, Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England [ 96 ] Vaasa Hlth Care Ctr, Vaasa, Finland [ 97 ] Brigham & Womens Hosp, Div Endocrinol & Metab, Boston, MA 02115 USA [ 98 ] Harvard Univ, Sch Med, Boston, MA USA [ 99 ] Univ Exeter, Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter, Devon, England [ 100 ] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China [ 101 ] Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden [ 102 ] Karolinska Univ, Hosp Solna, Ctr Mol Med, Stockholm, Sweden [ 103 ] Helmholtz Zentrum Muenchen, Inst Genet Epidemiol, Neuherberg, Germany [ 104 ] Helmholtz Zentrum Muenchen, Res Unit Mol Epidemiol, Neuherberg, Germany [ 105 ] Univ Munich, Clin Cooperat Grp Diabet, Munich, Germany [ 106 ] Helmholtz Zentrum Muenchen, Munich, Germany [ 107 ] Tech Univ Munich, Clin Cooperat Grp Nutrigen & Type Diabet 2, Munich, Germany [ 108 ] German Ctr Diabet Res DZD, Neuherberg, Germany [ 109 ] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England [ 110 ] Univ Tokyo, Grad Sch Med, Dept Diabet & Metab Dis, Tokyo, Japan [ 111 ] Univ Exeter, Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter, Devon, England [ 112 ] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany [ 113 ] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, Levanger, Norway [ 114 ] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands [ 115 ] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA [ 116 ] Univ Western Australia, Sch Populat Hlth, Nedlands, WA 6009, Australia [ 117 ] UCL, Inst Cardiovasc Sci, London, England [ 118 ] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA [ 119 ] Kinki Univ, Sch Med, Dept Diabet Endocrinol & Metab, Osaka 589, Japan [ 120 ] Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany [ 121 ] Univ Uppsala Hosp, Dept Mol Sci, Mol Epidemiol & Sci Life Lab, Uppsala, Sweden [ 122 ] Aga Khan Univ, Dept Community Hlth Sci, Karachi, Pakistan [ 123 ] Dept Social Serv & Hlth Care, Pietarsaari, Finland [ 124 ] Aga Khan Univ, Dept Med, Karachi, Pakistan [ 125 ] Queen Elizabeth II Med Ctr, West Australian Sleep Disorders Res Inst, Dept Pulm Physiol & Sleep Med, Nedlands, WA, Australia [ 126 ] Univ Western Australia, Sch Med & Pharmacol, Nedlands, WA 6009, Australia [ 127 ] Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany [ 128 ] Heart & Diabet Inst, Baker Int Diabet Inst IDI, Melbourne, Australia [ 129 ] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA [ 130 ] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA [ 131 ] Natl Ctr Global Hlth & Med, Res Inst, Shinjuku Ku, Tokyo, Japan [ 132 ] Univ Colombo, Dept Clin Med, Diabet Res Unit, Colombo, Sri Lanka [ 133 ] Univ Oulu, Inst Hlth Sci, Fac Med, Oulu, Finland [ 134 ] Oulu Univ Hosp, Unit Gen Practice, Oulu, Finland [ 135 ] Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore [ 136 ] Ewha Womans Univ, Sch Med, Dept Biochem, Seoul, South Korea [ 137 ] Soongsil Univ, Sch Syst Biomed Sci, Seoul, South Korea [ 138 ] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland [ 139 ] deCODE Genet, Reykjavik, Iceland [ 140 ] South Ostrobothnia Cent Hosp, Seinajoki, Finland [ 141 ] Minist Hlth, Port Louis, Mauritius [ 142 ] Univ Toronto, Dept Anthropol, Mississauga, ON L5L 1C6, Canada [ 143 ] Fdn IMSS, Mexico City, DF, Mexico [ 144 ] Univ Eastern Finland, Dept Med, Kuopio, Finland [ 145 ] Kuopio Univ Hosp, SF-70210 Kuopio, Finland [ 146 ] Kuopio Res Inst Exercise Med, Kuopio, Finland [ 147 ] Univ Western Australia, Ctr Genet Epidemiol & Biostat, Nedlands, WA 6009, Australia [ 148 ] Univ San Carlos, Off Populat Studies Fdn Inc, Cebu, Philippines [ 149 ] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Natl Heart & Lung Inst, London, England [ 150 ] Univ N Carolina, Dept Genet, Chapel Hill, NC USA [ 151 ] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA [ 152 ] Beijing Genom Inst, Shenzhen, Peoples R China [ 153 ] Uppsala Univ, Akad Sjukhuset, Dept Med Sci, Uppsala, Sweden [ 154 ] Mt Sinai Sch Med, Charles R Bronfman Inst Personalized Med, New York, NY USA [ 155 ] Mt Sinai Sch Med, Child Hlth & Dev Inst, New York, NY USA [ 156 ] Mt Sinai Sch Med, Dept Prevent Med, New York, NY USA [ 157 ] Shanghai Inst Prevent Med, Shanghai, Peoples R China [ 158 ] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA [ 159 ] Dr Mohans Diabet Specialties Ctr, Madras, Tamil Nadu, India [ 160 ] Univ Bonn, Inst Human Genet, Bonn, Germany [ 161 ] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany [ 162 ] Univ Munich, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany [ 163 ] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany [ 164 ] Sir Charles Gairdner Hosp, Nedlands, WA 6009, Australia [ 165 ] Nagoya Univ, Grad Sch Med, Div Endocrinol & Diabet, Dept Internal Med, Nagoya, Aichi 4648601, Japan [ 166 ] Chubu Rosai Hosp, Dept Endocrinol & Diabet, Nagoya, Aichi, Japan [ 167 ] Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway [ 168 ] Kyushu Univ, Grad Sch Med Sci, Dept Geriatr Med, Higashi Ku, Fukuoka 812, Japan [ 169 ] Churchill Hosp, Hlth Res Biomed Res Ctr, Oxford Natl Inst, Oxford OX3 7LJ, England [ 170 ] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA [ 171 ] Seoul Natl Univ, Grad Sch Convergence Sci & Technol, Dept Mol Med & Biopharmaceut Sci, World Class Univ Program, Seoul, South Korea [ 172 ] Seoul Natl Univ, Coll Med, Seoul, South Korea [ 173 ] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden [ 174 ] Inst Mol Med Finland FIMM, Helsinki, Finland [ 175 ] Helmholtz Zentrum Muenchen, Inst Epidemiol 2, Neuherberg, Germany [ 176 ] Univ Kelaniya, Fac Med, Dept Publ Hlth, Ragama, Sri Lanka [ 177 ] Nord Trondelag Hlth Trust, Levanger Hosp, Dept Internal Med, Levanger, Norway [ 178 ] Univ Gen Hosp Attikon, Athens, Greece [ 179 ] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Biometr & Epidemiol, Dusseldorf, Germany [ 180 ] Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, SF-70210 Kuopio, Finland [ 181 ] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA [ 182 ] Partners Ctr Personalized Genom Med, Boston, MA USA [ 183 ] Univ Dusseldorf, Dept Endocrinol & Diabetol, Dusseldorf, Germany [ 184 ] Univ Dusseldorf, Dept Metab Dis, Dusseldorf, Germany [ 185 ] Harvard Univ, Hlth Sci & Technol MD Program, Boston, MA 02115 USA [ 186 ] MIT, Boston, MA USA [ 187 ] Harvard Univ, Harvard Biol & Biomed Sci Program, Boston, MA 02115 USA [ 188 ] Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA [ 189 ] Finnish Diabet Assoc, Tampere, Finland [ 190 ] Pirkanmaa Hosp Dist, Tampere, Finland [ 191 ] Cent Finland Cent Hosp, Dept Med, Jyvaskyla, Finland [ 192 ] South Karelia Cent Hosp, Lappeenranta, Finland [ 193 ] UCL, Dept Genet Evolut & Environm, Genet Inst, London, England [ 194 ] Diabet Assoc Pakistan, Karachi, Pakistan [ 195 ] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA [ 196 ] Baltimore Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Baltimore, MD USA [ 197 ] Univ Maryland, Sch Med, Program Personalised & Genom Med, Baltimore, MD 21201 USA [ 198 ] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands [ 199 ] Univ Ulm, Dept Clin Chem, D-89069 Ulm, Germany [ 200 ] Univ Ulm, Cent Lab, D-89069 Ulm, Germany [ 201 ] Uppsala Univ, Dept Med Sci, Uppsala, Sweden [ 202 ] Kyushu Univ, Grad Sch Med Sci, Dept Internal Med & Bioregulatory Sci, Higashi Ku, Fukuoka 812, Japan [ 203 ] Univ Helsinki, Helsinki Univ Hosp, Dept Med, Helsinki, Finland [ 204 ] Hosp Univ LaPaz IdiPAZ, Inst Invest Sanitaria, Madrid, Spain [ 205 ] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria [ 206 ] King Abdulaziz Univ, Diabet Res Grp, Jeddah 21413, Saudi Arabia [ 207 ] IMSS, Ctr Med Nacl Siglo 21, Hosp Especialidades, Unidad Invest Med Bioquim, Mexico City, DF, Mexico [ 208 ] Univ Penn, Perelman Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA [ 209 ] Univ Melbourne, Ctr Eye Res Australia, East Melbourne, Vic, Australia [ 210 ] Kyushu Univ, Med Inst Bioregulat, Res Ctr Genet Informat, Div Genome Anal,Higashi Ku, Fukuoka 812, Japan [ 211 ] Univ Lille 1, Math Lab, CNRS UMR 8524, MODAL Team,INRIA Lille Nord Europe, F-59655 Villeneuve Dascq, France [ 212 ] Aichi Gakuin Univ, Sch Dent, Dept Genome Sci, Nagoya, Aichi 464, Japan [ 213 ] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA [ 214 ] Harvard Univ, Sch Med, Dept Mol Biol, Boston, MA USA [ 215 ] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA [ 216 ] Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA [ 217 ] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA [ 218 ] Hallym Univ, Dept Biomed Sci, Chunchon, Gangwon Do, South Korea [ 219 ] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA [ 220 ] Imperial Coll Healthcare NHS Trust, London, England [ 221 ] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA [ 222 ] Blood Syst Res Inst, San Francisco, CA USA [ 223 ] Natl Univ Singapore, Grad Sch Integrat Sci & Engn, Singapore 117548, Singapore [ 224 ] Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117548, Singapore [ 225 ] Natl Univ Singapore, Dept Med, Singapore 117548, Singapore [ 226 ] Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore [ 227 ] Univ Liverpool, Dept Biostat, Liverpool L69 3BX, Merseyside, England, Obstetrics & Gynecology, Radiology & Nuclear Medicine, Surgery, Epidemiology, Dermatology, Internal Medicine, Medical Microbiology & Infectious Diseases, Medical Research Council (MRC), National Institute for Health Research, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, and Cardiology

Subjects
CHROMATIN, endocrine system diseases, South Asian Type 2 Diabetes (SAT2D) Consortium, SCALE ASSOCIATION ANALYSIS, Medizin, LOCI, Genome-wide association study, VARIANTS, 0302 clinical medicine, Risk Factors, IMPUTATION, Glucose homeostasis, 11 Medical and Health Sciences, Genetics & Heredity, Genetics, 0303 health sciences, IDENTIFY, Hispanic or Latino, 3. Good health, MAP, POPULATIONS, Medical genetics, Type 2 Diabetes Genetic Exploration by Nex-generation sequencing in muylti-Ethnic Samples (T2D-GENES) Consortium, Hispanic Americans, Life Sciences & Biomedicine, Asian Continental Ancestry Group, medicine.medical_specialty, European Continental Ancestry Group, TRANSETHNIC METAANALYSIS, 030209 endocrinology & metabolism, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Article, White People, Sykursýki, 03 medical and health sciences, Asian People, SDG 3 - Good Health and Well-being, medicine, Humans, Genetic Predisposition to Disease, Allele, Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium, Alleles, 030304 developmental biology, Genetic association, Science & Technology, DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Mexican American Type 2 Diabetes (MAT2D) Consortium, 06 Biological Sciences, Arfgengi, Genetic architecture, INDIVIDUALS, Diabetes Mellitus, Type 2, Case-Control Studies, GLUCOSE-HOMEOSTASIS, ASSOCIATION ANALYSES, Imputation (genetics), Developmental Biology, Genome-Wide Association Study
Abstract

To access publisher's full text version of this article click on the hyperlink at the bottom of the page To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry. Canadian Institutes of Health Research Medical Research Council UK G0601261 Mexico Convocatoria SSA/IMMS/ISSSTE-CONACYT 2012-2 clave 150352 IMSS R-2011-785-018 CONACYT Salud-2007-C01-71068 US National Institutes of Health DK062370 HG000376 DK085584 DK085545 DK073541 DK085501 Wellcome Trust WT098017 WT090532 WT090367 WT098381 WT081682 WT085475 info:eu-repo/grantAgreement/EC/FP7/201413

Published
2014

10. The Pakistan Risk of Myocardial Infarction Study: a resource for the study of genetic, lifestyle and other determinants of myocardial infarction in South Asia

Author

Madiha Yameen, Muhammad Javed, Danish Saleheen, Nadeem Hayat Mallick, Syed Saadat Ali, Panos Deloukas, Ayeesha Kamran Kamal, Liaquat Ali Cheema, Waleed T. Kayani, Asad Ali Shah, Nabi Shah, Moazzam Zaidi, Muhammad Shazad, Sobia Naz, Muhammed Murtaza, Maria Samuel, Zia Yaqoob, Ali Raza Gardezi, Muhammad Salman Daood, Abdus Samad, Aisha Nazir, Rashid Jooma, Nadir Khan, Sana Nasim, Altaf Hussain, Farina Hanif, Usman Ahmad, Aisha Sultana, Muhammad Azhar, Muhammad Imran Nisar, Fazal-ur-Rehman, Syed Zahed Rasheed, Nadeem Sarwar, Abdul Ghaffar, Assadullah Kundi, Philippe M. Frossard, Shehzad Raza, Abdul Hakeem, Muhammad Ishaq, Azhar Faruqui, Nazir Ahmed Memon, John Danesh, Asif Rasheed, Khan Shah Zaman, and Mehmood Jafree

Subjects
Adult, Candidate gene, medicine.medical_specialty, Asia, Genotype, Epidemiology, Myocardial Infarction, 030204 cardiovascular system & hematology, Article, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Surveys and Questionnaires, Environmental health, Humans, Medicine, Genetic Predisposition to Disease, Pakistan, Myocardial infarction, Family history, Life Style, Aged, Retrospective Studies, 030304 developmental biology, Aged, 80 and over, 0303 health sciences, Anthropometry, business.industry, Public health, Case-control study, Retrospective cohort study, Middle Aged, medicine.disease, 3. Good health, Cardiovascular Diseases, business
Abstract

The burden of coronary heart disease (CHD) is increasing at a greater rate in South Asia than in any other region globally, but there is little direct evidence about its determinants. The Pakistan Risk of Myocardial Infarction Study (PROMIS) is an epidemiological resource to enable reliable study of genetic, lifestyle and other determinants of CHD in South Asia. By March 2009, PROMIS had recruited over 5,000 cases of first-ever confirmed acute myocardial infarction (MI) and over 5,000 matched controls aged 30–80 years. For each participant, information has been recorded on demographic factors, lifestyle, medical and family history, anthropometry, and a 12-lead electrocardiogram. A range of biological samples has been collected and stored, including DNA, plasma, serum and whole blood. During its next stage, the study aims to expand recruitment to achieve a total of about 20,000 cases and about 20,000 controls, and, in subsets of participants, to enrich the resource by collection of monocytes, establishment of lymphoblastoid cell lines, and by resurveying participants. Measurements in progress include profiling of candidate biochemical factors, assay of 45,000 variants in 2,100 candidate genes, and a genomewide association scan of over 650,000 genetic markers. We have established a large epidemiological resource for CHD in South Asia. In parallel with its further expansion and enrichment, the PROMIS resource will be systematically harvested to help identify and evaluate genetic and other determinants of MI in South Asia. Findings from this study should advance scientific understanding and inform regionally appropriate disease prevention and control strategies.

Published
2009

11. Lipoprotein(a) and coronary disease—moving closer to causality

Author

John Danesh and Sebhat Erqou

Subjects
medicine.medical_specialty, biology, business.industry, Lipoprotein(a), Coronary disease, Causality, Coronary heart disease, Coronary risk, Internal medicine, biology.protein, Cardiology, Medicine, Risk factor, Cardiology and Cardiovascular Medicine, business, Lipoprotein
Abstract

Lipoprotein(a) has been studied as a risk factor for coronary heart disease, but whether a causal relationship exists has been unclear. A study by Kamstrup and colleagues examining genetically mediated increases in lipoprotein(a) concentration now provides evidence that it could indeed represent a causal coronary risk factor.

Published
2009

12. BRCA2 variants and cardiovascular disease in a multi-ethnic study

Author

Robert A. Hegele, Danish Saleheen, Sonia S. Anand, James C. Engert, Kevin Zbuk, Matthew B. Lanktree, Robin Young, Ruby Miller, Salim Yusuf, Guillaume Paré, Changchun Xie, Mahyar Heydarpour, A. Darlene Davis, John Danesh, Danesh, John [0000-0003-1158-6791], and Apollo - University of Cambridge Repository

Subjects
lcsh:Internal medicine, Linkage disequilibrium, lcsh:QH426-470, Genotype, Genes, BRCA2, Disease, Biology, medicine.disease_cause, Polymorphism, Single Nucleotide, Linkage Disequilibrium, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, Genetics, medicine, Humans, Genetics(clinical), Genetic Predisposition to Disease, Allele, lcsh:RC31-1245, Genetics (clinical), Alleles, 030304 developmental biology, 0303 health sciences, Mutation, medicine.disease, Human genetics, 3. Good health, lcsh:Genetics, Cardiovascular Diseases, 030220 oncology & carcinogenesis, Cancer research, Ovarian cancer, Research Article
Abstract

Background Germline mutations of BRCA1/2 are associated with hereditary breast and ovarian cancer. Recent data suggests excess mortality in mutation carriers beyond that conferred by neoplasia, and recent in vivo and in vitro studies suggest a modulatory role for BRCA proteins in endothelial and cardiomyocyte function. We therefore tested the association of BRCA2 variants with clinical cardiovascular disease (CVD). Methods Using data from 1,170 individuals included in two multi-ethnic population-based studies (SHARE and SHARE-AP), the association between BRCA2 variants and CVD was evaluated. 15 SNPs in BRCA2 with minor allele frequencies (MAF) > 0.01 had been previously genotyped using the cardiovascular gene-centric 50 k SNP array. 115 individuals (9.8%) reported a CVD event, defined as myocardial infarction (MI), angina, silent MI, stroke, and angioplasty or coronary artery bypass surgery. Analyses were adjusted for age and sex. The SNPs rs11571836 and rs1799943 were subsequently genotyped using the MassARRAY platform in 1,045 cases of incident MI and 1,135 controls from the South Asian subset of an international case-control study of acute MI (INTERHEART), and rs11571836 was imputed in 4,686 cases and 4500 controls from the Pakistan Risk of Myocardial Infarction Study (PROMIS). Results Two BRCA2 SNPs, rs11571836 and rs1799943, both located in untranslated regions, were associated with lower risk of CVD (OR 0.47 p = 0.01 and OR 0.56 p = 0.03 respectively) in the SHARE studies. Analysis by specific ethnicities demonstrated an association with CVD for both SNPs in Aboriginal People, and for rs11571836 only in South Asians. No association was observed in the European and Chinese subgroups. A non-significant trend towards an association between rs11571836 and lower risk of MI was observed in South Asians from INTERHEART [OR = 0.87 (95% CI: 0.75-1.01) p = 0.068], but was not evident in PROMIS [OR = 0.96 (95% CI: 0.90-1.03) p = 0.230]. Meta-analysis of both case-control studies resulted in a combined OR of 0.94 (95% CI: 0.89-1.004, p = 0.06). Conclusions Although there was an association between two SNPs in BRCA2 and CVD in a multi-ethnic population, these results were not replicated in two South Asian case-control studies of incident MI. Future studies exploring the association between BRCA variants and cardiovascular disorders are needed to clarify the role, if any, for BRCA variants in CVD pathogenesis.

Published
2012

13. EPIC-Heart: The cardiovascular component of a prospective study of nutritional, lifestyle and biological factors in 520,000 middle-aged participants from 10 European countries

Author

Kay-Tee Khaw, Göran Hallmans, Concepción Moreno Iribas, Nadia Slimani, María José Sánchez Pérez, Dimitrios Trichopoulos, Anne Tjønneland, Agnès Fournier, Françoise Clavel-Chapelon, Heiner Boeing, Edith J. M. Feskens, Rosario Tumino, Jakob Linseisen, Kim Overvad, Søren Paaske Johnsen, Tobias Pischon, Yvonne T. van der Schouw, Majken K. Jensen, Carlos Alberto Gonzalez Svatetz, Giovanna Masala, Sabina Sieri, Nicholas J. Wareham, Cornelia Weikert, Vassiliki Benetou, Elio Riboli, Simon G. Thompson, Rodolfo Saracci, Merethe Kumle, Anja Olsen, W. M. Monique Verschuren, Diederick E. Grobbee, Sheila Bingham, Antonia Trichopoulou, Nerea Larrañaga, Pietro Ferrari, Salvatore Panico, Guri Skeie, Amalia Mattiello, Timothy J. Key, Andrew W. Roddam, José Ramón Quirós, Patrik Wennberg, Göran Berglund, John Danesh, Carlotta Sacerdote, Marianne Canonico, Eiliv Lund, Rudolf Kaaks, Carmen Navarro Sánchez, Olle Melander, H. Bas Bueno-de-Mesquita, Teresa Norat, Department of Public Health & Primary Care, University of Cambridge [UK] (CAM), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Department of Clinical Sciences, Lund University [Lund]-Malmö University Hospital, Division of Human Nutrition, Wageningen University and Research [Wageningen] (WUR), Department of Clinical Epidemiology, Aarhus University Hospital, Department of Clinical and Experimental Medicine, University of Naples Federico II = Università degli studi di Napoli Federico II, Plasmon Nano-optics, Institut de Ciencies Fotoniques [Castelldefels] (ICFO), Nutrition, hormones et cancer: épidémiologie et prévention (E3N), Epidémiologie, sciences sociales, santé publique (IFR 69), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM UNIT 780: Epidemiology and biostatistics, Paul-Brousse Hospital, Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Institute of Cancer Epidemiology, Danish Cancer Society, Centre for Ice and Climate [Copenhagen], Niels Bohr Institute [Copenhagen] (NBI), Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Public Health and Health Planning Directorate, Gobierno del Principado de Asturias-Consejeria de Salud y Servicios Sanitarios, Catalan Institute of Oncology, Matériaux, ingénierie et science [Villeurbanne] (MATEIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Public Health Department of Gipuzkoa, Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Public Health Institute of Navarra, MRC Centrer for Nutritional Epidemiology and Cancer Prevention and Survival, Clinical Gerontology Unit, MRC epidemiology Unit, Addenbrooke's Hospital, Cancer Epidemiology Unit, University of Oxford, Cancer Research UK Epidemiology Unit, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens], WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Molecular and Nutritional Epidemiology Unit (ISPO), Cancer Research and Prevention Institute, Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Cancer Registry and Histopathology Unit, Civile - M.P.Arezzo Hospital, Center for Cancer Prevention, CPO-Piemonte, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], Department of Medecine, Skellefteå Hospital, Skellefteå Hospital, Skellefteå, Suède, Institute of Community Medicine University of Tromsø, Centro Ricerche Produzioni Animali (CRPA), Dietary Exposure Assessment Grp, Int Agcy Res Canc, School of Public Health, Imperial College London, Department of Epidemiology and Biostatistics, SZTAJNBOK, Pascale, IRCCS Istituto Nazionale dei Tumori [Milano], Università degli studi di Napoli Federico II, Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC), University of Oxford [Oxford], and University Medical Centre Utrecht

Subjects
Male, Gerontology, coronary-artery-disease, Nutrition and Disease, Epidemiology, population, 030204 cardiovascular system & hematology, Coronary artery disease, 0302 clinical medicine, Voeding en Ziekte, Surveys and Questionnaires, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, risk, education.field_of_study, Anthropometry, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Cardiovascular Diseases, fat distribution, Female, women, prospective study, Adult, medicine.medical_specialty, Population, Nutritional Status, 03 medical and health sciences, medicine, Humans, cancer, plasma-levels, ddc:610, education, Life Style, dietary assessment methods, VLAG, Aged, Global Nutrition, Wereldvoeding, business.industry, Public health, norfolk cohort, medicine.disease, Middle age, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, high blood-pressure, EPIC Heart, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, diet, business, study protocol
Abstract

International audience; EPIC-Heart is the cardiovascular component of the European Prospective Investigation into Cancer and Nutrition (EPIC), a multi-centre prospective cohort study investigating the relationship between nutrition and major chronic disease outcomes. Its objective is to advance understanding about the separate and combined influences of lifestyle (especially dietary), environmental, metabolic and genetic factors in the development of cardiovascular diseases by making best possible use of the unusually informative database and biological samples in EPIC. Between 1992 and 2000, 519,978 participants (366,521 women and 153,457 men, mostly aged 35-70 years) in 23 centres in 10 European countries commenced follow-up for cause- specific mortality, cancer incidence and major cardiovascular morbidity. Dietary information was collected with quantitative questionnaires or semi-quantitative food frequency questionnaires, including a 24-h dietary recall sub-study to help calibrate the dietary measurements. Information was collected on physical activity, tobacco smoking, alcohol consumption, occupational history, socio-economic status, and history of previous illnesses. Anthropometric measurements and blood pressure recordings were made in the majority of participants. Blood samples were taken from 385,747 individuals, from which plasma, serum, red cells, and buffy coat fractions were separated and aliquoted for long-term storage. By 2004, an estimated 10,000 incident fatal and non-fatal coronary and stroke events had been recorded. The first cycle of EPIC-Heart analyses will assess associations of coronary mortality with several prominent dietary hypotheses and with established cardiovascular risk factors. Subsequent analyses will extend this approach to non-fatal cardiovascular outcomes and to further dietary, biochemical and genetic factors.

Published
2007

14. A human germ project?

Author

Robert U. Newton, Valerie Beral, and John Danesh

Subjects
medicine.medical_specialty, Multidisciplinary, Chlamydia, biology, business.industry, Peptic, Helicobacter pylori, biology.organism_classification, medicine.disease, Virology, Coronary heart disease, Epidemiology, Medicine, business, Sequence (medicine)
Abstract

A few weeks ago,Nature reported the sequence of Helicobacter pylori, which is present in up to one in three people and causes peptic ulcers. But many other chronic diseases or cancers are also thought to be caused by infectious agents. Weight is now lent to this theory by two studies that link coronary heart disease to the bacterium Chlamydia pneumoniae, and the implications of these findings are discussed.

Published
1997

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