Association between C reactive protein and coronary heart disease: mendelian randomisation analysis based on individual participant data
G. Eiriksdottir,T. B. Harris,L. J. Launer,Vilmundur Gudnason,Aaron R. Folsom,Gavin Andrews,C. M. Ballantyne,Nilesh J. Samani,A. S. Hall,P. S. Braund,A. J. Balmforth,Peter H. Whincup,Richard W Morris,Debbie A Lawlor,Gordon D.O. Lowe,Nicholas J. Timpson,Shah Ebrahim,Yoav Ben-Shlomo,George Davey-Smith,Børge G. Nordestgaard,Anne Tybjærg-Hansen,Jeppe Zacho,Matthew A. Brown,Manjinder S. Sandhu,Sally L. Ricketts,Sofie Ashford,Leslie A. Lange,Alexander P. Reiner,Mary Cushman,Russel Tracy,C. Wu,J. Ge,Y. Zou,A. Sun,Joseph Hung,Brendan McQuillan,Peter L. Thompson,John Beilby,Nicole M. Warrington,Lyle J. Palmer,Christoph Wanner,Christiane Drechsler,Michael Hoffmann,F. G. R. Fowkes,Ioanna Tzoulaki,Meena Kumari,Michelle A. Miller,Michael Marmot,Charlotte Onland-Moret,Y. T. van der Schouw,J.M.A. Boer,Cisca Wijmenga,Kay-Tee Khaw,Ramachandran S. Vasan,Renate B. Schnabel,J. F. Yamamoto,E J Benjamin,Heribert Schunkert,Jeanette Erdmann,Inke R. König,Christian Hengstenberg,Benedetta D. Chiodini,MariaGrazia Franzosi,Silvia Pietri,Francesca Gori,Megan E. Rudock,Yongmei Liu,Kurt Lohman,Steve E. Humphries,Anders Hamsten,Paul Norman,Graeme J. Hankey,Konrad Jamrozik,Eric B. Rimm,J. K. Pai,Bruce M. Psaty,Susan R. Heckbert,J. C. Bis,Salim Yusuf,Sonia S. Anand,Engert Jc,C. Xie,Ryan L. Collins,Robert Clarke,David L.H. Bennett,Jaspal S. Kooner,John C. Chambers,Paul Elliott,W. März,Marcus E. Kleber,Bernhard O. Böhm,Winkelmann Br,Olle Melander,Göran Berglund,Wolfgang Koenig,Barbara Thorand,Jens Baumert,Annette Peters,JoAnn E. Manson,J.A. Cooper,P.J. Talmud,Per Ladenvall,Lovisa Johansson,J. H. Jansson,Göran Hallmans,Muredach P. Reilly,Liming Qu,Man Li,Daniel J. Rader,Hugh Watkins,Jemma C. Hopewell,Danish Saleheen,John Danesh,Philippe M. Frossard,Naveed Sattar,Michele Robertson,J. Shepherd,Ernst J. Schaefer,A. Hofman,J. C. M. Witteman,Isabella Kardys,Abbas Dehghan,U de Faire,Anna M. Bennet,Bruna Gigante,Karin Leander,Bas J M Peters,A.H. Maitland-van der Zee,A.H. De Boer,Olaf H. Klungel,Philip Greenland,J. Dai,Simin Liu,Eric J. Brunner,Mika Kivimäki,Denis St. J. O’Reilly,Ian Ford,Chris J. Packard +137 more
- Vol. 342, Iss: 7794, pp 425
Reads0
Chats0
TLDR
Human genetic data indicate that C reactive protein concentration itself is unlikely to be even a modest causal factor in coronary heart disease.Abstract:
Objective To use genetic variants as unconfounded proxies of C reactive protein concentration to study its causal role in coronary heart disease. Design Mendelian randomisation meta-analysis of ind ...read more
Citations
More filters
Journal ArticleDOI
Mendelian randomization: genetic anchors for causal inference in epidemiological studies
George Davey Smith,Gibran Hemani +1 more
TL;DR: Developments of MR, including two-sample MR, bidirectional MR, network MR, two-step MR, factorial MR and multiphenotype MR, are outlined in this review.
Mendelianrandomization:geneticanchorsforcausal inference in epidemiological studies
George Davey Smith,Gibran Hemani +1 more
TL;DR: Mendelian randomization (MR) is a method that utilizes genetic variants that are robustly associated with such modifiable exposures to generate more reliable evidence regarding which interventions should produce health benefits.
Journal ArticleDOI
Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians
TL;DR: In this article, the authors provide explanations of the information typically reported in Mendelian randomisation studies that can be used to assess the plausibility of these assumptions and guidance on how to interpret findings from such studies in the context of other sources of evidence.
Journal ArticleDOI
The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis.
Daniel I. Swerdlow,Michael V. Holmes,Karoline Kuchenbaecker,Engmann Jel.,Tina Shah,Reecha Sofat,Yiran Guo,C Chung,Anne Peasey,Roman Pfister,Simon P. Mooijaart,Helen Ireland,Maarten Leusink,Claudia Langenberg,KaWah Li,Jutta Palmen,Phil Howard,Jackie A. Cooper,Fotios Drenos,John Hardy,Mike A. Nalls,Yun Li,Gordon D.O. Lowe,Marlene C. W. Stewart,S. J. Bielinski,Julian Peto,Nicholas J. Timpson,John Gallacher,Malcolm G. Dunlop,Richard S. Houlston,Ian Tomlinson,Ioanna Tzoulaki,Jian'an Luan,Boer Jma.,Nita G. Forouhi,N. C. Onland-Moret,Y. T. van der Schouw,Renate B. Schnabel,Jaroslav A. Hubacek,Růžena Kubínová,Migle Baceviciene,Abdonas Tamosiunas,Andrzej Pajak,Roman Topor-Madry,Sofia Malyutina,Damiano Baldassarre,Bengt Sennblad,Elena Tremoli,U de Faire,Luigi Ferrucci,S Bandenelli,Tetsu Tanaka,James F. Meschia,AB Singleton,Gerjan Navis,I. Mateo Leach,Bakker Sjl.,Ron T. Gansevoort,Ian Ford,Stephen E. Epstein,Mary-Susan Burnett,Joe Devaney,Johan Wouter Jukema,Westendorp Rgj.,G Jan de Borst,Y. van der Graaf,P A de Jong,Mailand-van der Zee A-H.,Olaf H. Klungel,A. de Boer,P. A. Doevendans,Jeffrey W. Stephens,Charles B. Eaton,Jennifer G. Robinson,JoAnn E. Manson,F G Fowkes,Timothy M. Frayling,Jenna Price,Peter H. Whincup,Richard W Morris,Debbie A Lawlor,George Davey Smith,Yoav Ben-Shlomo,Susan Redline,Leslie A. Lange,Meena Kumari,Nicholas J. Wareham,Verschuren Wmm.,Emelia J. Benjamin,John C. Whittaker,Anders Hamsten,Frank Dudbridge,Delaney Jac.,Andrew Wong,Diana Kuh,Rebecca Hardy,Berta Almoguera Castillo,John Connolly,P. van der Harst,Eric J. Brunner,Michael Marmot,Christina L. Wassel,Steve E. Humphries,P.J. Talmud,Mika Kivimäki,Folkert W. Asselbergs,Mikhail I. Voevoda,Martin Bobak,Hynek Pikhart,James G. Wilson,Hakon Hakonarson,Alexander P. Reiner,Brendan J. Keating,Naveed Sattar,Aroon D. Hingorani,Juan P. Casas +115 more
TL;DR: IL6R blockade could provide a novel therapeutic approach to prevention of coronary heart disease that warrants testing in suitably powered randomised trials and could help to validate and prioritise novel drug targets or to repurpose existing agents and targets for new therapeutic uses.
Journal ArticleDOI
Avoiding bias from weak instruments in Mendelian randomization studies
TL;DR: Bias is shown to increase as the expected F-statistic decreases, and can be reduced by using parsimonious models of genetic association (i.e. not over-parameterized) and by adjusting for measured covariates.
References
More filters
Journal ArticleDOI
Quantifying heterogeneity in a meta‐analysis
TL;DR: It is concluded that H and I2, which can usually be calculated for published meta-analyses, are particularly useful summaries of the impact of heterogeneity, and one or both should be presented in publishedMeta-an analyses in preference to the test for heterogeneity.
Journal ArticleDOI
Inflammation, Atherosclerosis, and Coronary Artery Disease
TL;DR: The evidence is recounted that atherosclerosis, the main cause of CAD, is an inflammatory disease in which immune mechanisms interact with metabolic risk factors to initiate, propagate, and activate lesions in the arterial tree.
Journal ArticleDOI
The International HapMap Project
John W. Belmont,Paul Hardenbol,Thomas D. Willis,Fuli Yu,Huanming Yang,Lan Yang Ch'Ang,Wei Huang,Bin Liu,Yan Shen,Paul K.H. Tam,Lap-Chee Tsui,Mary M.Y. Waye,Jeffrey Tze Fei Wong,Changqing Zeng,Qingrun Zhang,Mark S. Chee,Luana Galver,Semyon Kruglyak,Sarah S. Murray,Arnold Oliphant,Alexandre Montpetit,Fanny Chagnon,Vincent Ferretti,Martin Leboeuf,Michael S. Phillips,Andrei Verner,Shenghui Duan,Denise L. Lind,Raymond D. Miller,John P. Rice,Nancy L. Saccone,Patricia Taillon-Miller,Ming Xiao,Akihiro Sekine,Koki Sorimachi,Yoichi Tanaka,Tatsuhiko Tsunoda,Eiji Yoshino,David R. Bentley,Sarah E. Hunt,Don Powell,Houcan Zhang,Ichiro Matsuda,Yoshimitsu Fukushima,Darryl Macer,Eiko Suda,Charles N. Rotimi,Clement Adebamowo,Toyin Aniagwu,Patricia A. Marshall,Olayemi Matthew,Chibuzor Nkwodimmah,Charmaine D.M. Royal,Mark Leppert,Missy Dixon,Fiona Cunningham,Ardavan Kanani,Gudmundur A. Thorisson,Peter E. Chen,David J. Cutler,Carl S. Kashuk,Peter Donnelly,Jonathan Marchini,Gilean McVean,Simon Myers,Lon R. Cardon,Andrew P. Morris,Bruce S. Weir,James C. Mullikin,Michael Feolo,Mark J. Daly,Renzong Qiu,Alastair Kent,Georgia M. Dunston,Kazuto Kato,Norio Niikawa,Jessica Watkin,Richard A. Gibbs,Erica Sodergren,George M. Weinstock,Richard K. Wilson,Lucinda Fulton,Jane Rogers,Bruce W. Birren,Hua Han,Hongguang Wang,Martin Godbout,John C. Wallenburg,Paul L'Archevêque,Guy Bellemare,Kazuo Todani,Takashi Fujita,Satoshi Tanaka,Arthur L. Holden,Francis S. Collins,Lisa D. Brooks,Jean E. McEwen,Mark S. Guyer,Elke Jordan,Jane Peterson,Jack Spiegel,Lawrence M. Sung,Lynn F. Zacharia,Karen Kennedy,Michael Dunn,Richard Seabrook,Mark Shillito,Barbara Skene,John Stewart,David Valle,Ellen Wright Clayton,Lynn B. Jorde,Aravinda Chakravarti,Mildred K. Cho,Troy Duster,Troy Duster,Morris W. Foster,Maria Jasperse,Bartha Maria Knoppers,Pui-Yan Kwok,Julio Licinio,Jeffrey C. Long,Pilar N. Ossorio,Vivian Ota Wang,Charles N. Rotimi,Patricia Spallone,Patricia Spallone,Sharon F. Terry,Eric S. Lander,Eric H. Lai,Deborah A. Nickerson,Gonçalo R. Abecasis,David Altshuler,Michael Boehnke,Panos Deloukas,Julie A. Douglas,Stacey Gabriel,Richard R. Hudson,Thomas J. Hudson,Leonid Kruglyak,Yusuke Nakamura,Robert L. Nussbaum,Stephen F. Schaffner,Stephen T. Sherry,Lincoln Stein,Toshihiro Tanaka +145 more
TL;DR: The HapMap will allow the discovery of sequence variants that affect common disease, will facilitate development of diagnostic tools, and will enhance the ability to choose targets for therapeutic intervention.
Journal ArticleDOI
Markers of Inflammation and Cardiovascular Disease Application to Clinical and Public Health Practice: A Statement for Healthcare Professionals From the Centers for Disease Control and Prevention and the American Heart Association
Thomas A. Pearson,George A. Mensah,R. Wayne Alexander,Jeffrey L. Anderson,Richard O. Cannon,Michael H. Criqui,Yazid Y. Fadl,Stephen P. Fortmann,Yuling Hong,Gary L. Myers,Nader Rifai,Sidney C. Smith,Kathryn A. Taubert,Russell P. Tracy,Frank Vinicor +14 more
TL;DR: There has been no consensus from professional societies or governmental agencies as to how these assays of markers of inflammation should be used in clinical practice, and a workshop to address these issues was convened in Atlanta, Ga.
Journal ArticleDOI
WinBUGS – A Bayesian modelling framework: Concepts, structure, and extensibility
TL;DR: How and why various modern computing concepts, such as object-orientation and run-time linking, feature in the software's design are discussed and how the framework may be extended.
Related Papers (5)
‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease?
George Davey Smith,Shah Ebrahim +1 more