Literature DB >> 33663581

Genetic susceptibility, elevated blood pressure, and risk of atrial fibrillation: a Mendelian randomization study.

Milad Nazarzadeh1,2, Ana-Catarina Pinho-Gomes2, Zeinab Bidel1,2, Dexter Canoy1,2,3, Abbas Dehghan4, Karl Smith Byrne1, Derrick A Bennett5, George Davey Smith6, Kazem Rahimi7,8,9.   

Abstract

BACKGROUND: Whether elevated blood pressure (BP) is a modifiable risk factor for atrial fibrillation (AF) is not established. We tested (1) whether the association between BP and risk of AF is causal, (2) whether it varies according to individual's genetic susceptibility for AF, and (3) the extent to which specific BP-lowering drugs are expected to reduce this risk.
METHODS: First, causality of association was assessed through two-sample Mendelian randomization, using data from two independent genome-wide association studies that included a population of one million Europeans in total. Second, the UK Biobank data of 329,237 participants at baseline was used to study the effect of BP on AF according to genetic susceptibility of developing AF. Third, a possible treatment effect with major BP-lowering drug classes on AF risk was predicted through genetic variants in genes encode the therapeutic targets of each drug class. Estimated drug effects were compared with effects on incident coronary heart disease, for which direct trial evidence exists.
RESULTS: The two-sample Mendelian randomization analysis indicated that, on average, exposure to a higher systolic BP increased the risk of AF by 19% (odds ratio per each 10-mmHg [OR] 1.19 [1.12 to 1.27]). This association was replicated in the UK biobank using individual participant data. However, in a further genetic risk-stratified analysis, there was evidence for a linear gradient in the relative effects of systolic BP on AF; while there was no conclusive evidence of an effect in those with low genetic risk, a strong effect was observed among those with high genetic susceptibility for AF. The comparison of predicted treatment effects using genetic proxies for three main drug classes (angiotensin-converting enzyme inhibitors, beta-blockers, and calcium channel blockers) suggested similar average effects for the prevention of atrial fibrillation and coronary heart disease.
CONCLUSIONS: The effect of elevated BP on the risk of AF is likely to be causal, suggesting that BP-lowering treatment may be effective in AF prevention. However, average effects masked clinically important variations, with a more pronounced effect in individuals with high genetic susceptibility risk for AF.

Entities:  

Keywords:  Atrial fibrillation; Blood pressure; Mendelian randomization

Mesh:

Year:  2021        PMID: 33663581      PMCID: PMC7934395          DOI: 10.1186/s13073-021-00849-3

Source DB:  PubMed          Journal:  Genome Med        ISSN: 1756-994X            Impact factor:   15.266


  39 in total

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James F Wilson; Luigi Ferrucci; Martin Farrall; Jaakko Tuomilehto; Peter P Pramstaller; Roberto Elosua; Nicole Soranzo; Eric J G Sijbrands; David Altshuler; Ruth J F Loos; Alan R Shuldiner; Christian Gieger; Pierre Meneton; Andre G Uitterlinden; Nicholas J Wareham; Vilmundur Gudnason; Jerome I Rotter; Rainer Rettig; Manuela Uda; David P Strachan; Jacqueline C M Witteman; Anna-Liisa Hartikainen; Jacques S Beckmann; Eric Boerwinkle; Ramachandran S Vasan; Michael Boehnke; Martin G Larson; Marjo-Riitta Järvelin; Bruce M Psaty; Gonçalo R Abecasis; Aravinda Chakravarti; Paul Elliott; Cornelia M van Duijn; Christopher Newton-Cheh; Daniel Levy; Mark J Caulfield; Toby Johnson
Journal:  Nature       Date:  2011-09-11       Impact factor: 49.962

5.  The MR-Base platform supports systematic causal inference across the human phenome.

Authors:  Gibran Hemani; Jie Zheng; Benjamin Elsworth; Tom R Gaunt; Philip C Haycock; Kaitlin H Wade; Valeriia Haberland; Denis Baird; Charles Laurin; Stephen Burgess; Jack Bowden; Ryan Langdon; Vanessa Y Tan; James Yarmolinsky; Hashem A Shihab; Nicholas J Timpson; David M Evans; Caroline Relton; Richard M Martin; George Davey Smith
Journal:  Elife       Date:  2018-05-30       Impact factor: 8.140

6.  Impact of common genetic variation on response to simvastatin therapy among 18 705 participants in the Heart Protection Study.

Authors:  Jemma C Hopewell; Sarah Parish; Alison Offer; Emma Link; Robert Clarke; Mark Lathrop; Jane Armitage; Rory Collins
Journal:  Eur Heart J       Date:  2012-10-24       Impact factor: 29.983

7.  Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.

Authors:  Evangelos Evangelou; Helen R Warren; David Mosen-Ansorena; Borbala Mifsud; Raha Pazoki; He Gao; Georgios Ntritsos; Niki Dimou; Claudia P Cabrera; Ibrahim Karaman; Fu Liang Ng; Marina Evangelou; Katarzyna Witkowska; Evan Tzanis; Jacklyn N Hellwege; Ayush Giri; Digna R Velez Edwards; Yan V Sun; Kelly Cho; J Michael Gaziano; Peter W F Wilson; Philip S Tsao; Csaba P Kovesdy; Tonu Esko; Reedik Mägi; Lili Milani; Peter Almgren; Thibaud Boutin; Stéphanie Debette; Jun Ding; Franco Giulianini; Elizabeth G Holliday; Anne U Jackson; Ruifang Li-Gao; Wei-Yu Lin; Jian'an Luan; Massimo Mangino; Christopher Oldmeadow; Bram Peter Prins; Yong Qian; Muralidharan Sargurupremraj; Nabi Shah; Praveen Surendran; Sébastien Thériault; Niek Verweij; Sara M Willems; Jing-Hua Zhao; Philippe Amouyel; John Connell; Renée de Mutsert; Alex S F Doney; Martin Farrall; Cristina Menni; Andrew D Morris; Raymond Noordam; Guillaume Paré; Neil R Poulter; Denis C Shields; Alice Stanton; Simon Thom; Gonçalo Abecasis; Najaf Amin; Dan E Arking; Kristin L Ayers; Caterina M Barbieri; Chiara Batini; Joshua C Bis; Tineka Blake; Murielle Bochud; Michael Boehnke; Eric Boerwinkle; Dorret I Boomsma; Erwin P Bottinger; Peter S Braund; Marco Brumat; Archie Campbell; Harry Campbell; Aravinda Chakravarti; John C Chambers; Ganesh Chauhan; Marina Ciullo; Massimiliano Cocca; Francis Collins; Heather J Cordell; Gail Davies; Martin H de Borst; Eco J de Geus; Ian J Deary; Joris Deelen; Fabiola Del Greco M; Cumhur Yusuf Demirkale; Marcus Dörr; Georg B Ehret; Roberto Elosua; Stefan Enroth; A Mesut Erzurumluoglu; Teresa Ferreira; Mattias Frånberg; Oscar H Franco; Ilaria Gandin; Paolo Gasparini; Vilmantas Giedraitis; Christian Gieger; Giorgia Girotto; Anuj Goel; Alan J Gow; Vilmundur Gudnason; Xiuqing Guo; Ulf Gyllensten; Anders Hamsten; Tamara B Harris; Sarah E Harris; Catharina A Hartman; Aki S Havulinna; Andrew A Hicks; Edith Hofer; Albert Hofman; Jouke-Jan Hottenga; Jennifer E Huffman; Shih-Jen Hwang; Erik Ingelsson; Alan James; Rick Jansen; Marjo-Riitta Jarvelin; Roby Joehanes; Åsa Johansson; Andrew D Johnson; Peter K Joshi; Pekka Jousilahti; J Wouter Jukema; Antti Jula; Mika Kähönen; Sekar Kathiresan; Bernard D Keavney; Kay-Tee Khaw; Paul Knekt; Joanne Knight; Ivana Kolcic; Jaspal S Kooner; Seppo Koskinen; Kati Kristiansson; Zoltan Kutalik; Maris Laan; Marty Larson; Lenore J Launer; Benjamin Lehne; Terho Lehtimäki; David C M Liewald; Li Lin; Lars Lind; Cecilia M Lindgren; YongMei Liu; Ruth J F Loos; Lorna M Lopez; Yingchang Lu; Leo-Pekka Lyytikäinen; Anubha Mahajan; Chrysovalanto Mamasoula; Jaume Marrugat; Jonathan Marten; Yuri Milaneschi; Anna Morgan; Andrew P Morris; Alanna C Morrison; Peter J Munson; Mike A Nalls; Priyanka Nandakumar; Christopher P Nelson; Teemu Niiranen; Ilja M Nolte; Teresa Nutile; Albertine J Oldehinkel; Ben A Oostra; Paul F O'Reilly; Elin Org; Sandosh Padmanabhan; Walter Palmas; Aarno Palotie; Alison Pattie; Brenda W J H Penninx; Markus Perola; Annette Peters; Ozren Polasek; Peter P Pramstaller; Quang Tri Nguyen; Olli T Raitakari; Meixia Ren; Rainer Rettig; Kenneth Rice; Paul M Ridker; Janina S Ried; Harriëtte Riese; Samuli Ripatti; Antonietta Robino; Lynda M Rose; Jerome I Rotter; Igor Rudan; Daniela Ruggiero; Yasaman Saba; Cinzia F Sala; Veikko Salomaa; Nilesh J Samani; Antti-Pekka Sarin; Reinhold Schmidt; Helena Schmidt; Nick Shrine; David Siscovick; Albert V Smith; Harold Snieder; Siim Sõber; Rossella Sorice; John M Starr; David J Stott; David P Strachan; Rona J Strawbridge; Johan Sundström; Morris A Swertz; Kent D Taylor; Alexander Teumer; Martin D Tobin; Maciej Tomaszewski; Daniela Toniolo; Michela Traglia; Stella Trompet; Jaakko Tuomilehto; Christophe Tzourio; André G Uitterlinden; Ahmad Vaez; Peter J van der Most; Cornelia M van Duijn; Anne-Claire Vergnaud; Germaine C Verwoert; Veronique Vitart; Uwe Völker; Peter Vollenweider; Dragana Vuckovic; Hugh Watkins; Sarah H Wild; Gonneke Willemsen; James F Wilson; Alan F Wright; Jie Yao; Tatijana Zemunik; Weihua Zhang; John R Attia; Adam S Butterworth; Daniel I Chasman; David Conen; Francesco Cucca; John Danesh; Caroline Hayward; Joanna M M Howson; Markku Laakso; Edward G Lakatta; Claudia Langenberg; Olle Melander; Dennis O Mook-Kanamori; Colin N A Palmer; Lorenz Risch; Robert A Scott; Rodney J Scott; Peter Sever; Tim D Spector; Pim van der Harst; Nicholas J Wareham; Eleftheria Zeggini; Daniel Levy; Patricia B Munroe; Christopher Newton-Cheh; Morris J Brown; Andres Metspalu; Adriana M Hung; Christopher J O'Donnell; Todd L Edwards; Bruce M Psaty; Ioanna Tzoulaki; Michael R Barnes; Louise V Wain; Paul Elliott; Mark J Caulfield
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Authors:  Majid Nikpay; Anuj Goel; Hong-Hee Won; Leanne M Hall; Christina Willenborg; Stavroula Kanoni; Danish Saleheen; Theodosios Kyriakou; Christopher P Nelson; Jemma C Hopewell; Thomas R Webb; Lingyao Zeng; Abbas Dehghan; Maris Alver; Sebastian M Armasu; Kirsi Auro; Andrew Bjonnes; Daniel I Chasman; Shufeng Chen; Ian Ford; Nora Franceschini; Christian Gieger; Christopher Grace; Stefan Gustafsson; Jie Huang; Shih-Jen Hwang; Yun Kyoung Kim; Marcus E Kleber; King Wai Lau; Xiangfeng Lu; Yingchang Lu; Leo-Pekka Lyytikäinen; Evelin Mihailov; Alanna C Morrison; Natalia Pervjakova; Liming Qu; Lynda M Rose; Elias Salfati; Richa Saxena; Markus Scholz; Albert V Smith; Emmi Tikkanen; Andre Uitterlinden; Xueli Yang; Weihua Zhang; Wei Zhao; Mariza de Andrade; Paul S de Vries; Natalie R van Zuydam; Sonia S Anand; Lars Bertram; Frank Beutner; George Dedoussis; Philippe Frossard; Dominique Gauguier; Alison H Goodall; Omri Gottesman; Marc Haber; Bok-Ghee Han; Jianfeng Huang; Shapour Jalilzadeh; Thorsten Kessler; Inke R König; Lars Lannfelt; Wolfgang Lieb; Lars Lind; Cecilia M Lindgren; Marja-Liisa Lokki; Patrik K Magnusson; Nadeem H Mallick; Narinder Mehra; Thomas Meitinger; Fazal-Ur-Rehman Memon; Andrew P Morris; Markku S Nieminen; Nancy L Pedersen; Annette Peters; Loukianos S Rallidis; Asif Rasheed; Maria Samuel; Svati H Shah; Juha Sinisalo; Kathleen E Stirrups; Stella Trompet; Laiyuan Wang; Khan S Zaman; Diego Ardissino; Eric Boerwinkle; Ingrid B Borecki; Erwin P Bottinger; Julie E Buring; John C Chambers; Rory Collins; L Adrienne Cupples; John Danesh; Ilja Demuth; Roberto Elosua; Stephen E Epstein; Tõnu Esko; Mary F Feitosa; Oscar H Franco; Maria Grazia Franzosi; Christopher B Granger; Dongfeng Gu; Vilmundur Gudnason; Alistair S Hall; Anders Hamsten; Tamara B Harris; Stanley L Hazen; Christian Hengstenberg; Albert Hofman; Erik Ingelsson; Carlos Iribarren; J Wouter Jukema; Pekka J Karhunen; Bong-Jo Kim; Jaspal S Kooner; Iftikhar J Kullo; Terho Lehtimäki; Ruth J F Loos; Olle Melander; Andres Metspalu; Winfried März; Colin N Palmer; Markus Perola; Thomas Quertermous; Daniel J Rader; Paul M Ridker; Samuli Ripatti; Robert Roberts; Veikko Salomaa; Dharambir K Sanghera; Stephen M Schwartz; Udo Seedorf; Alexandre F Stewart; David J Stott; Joachim Thiery; Pierre A Zalloua; Christopher J O'Donnell; Muredach P Reilly; Themistocles L Assimes; John R Thompson; Jeanette Erdmann; Robert Clarke; Hugh Watkins; Sekar Kathiresan; Ruth McPherson; Panos Deloukas; Heribert Schunkert; Nilesh J Samani; Martin Farrall
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Authors:  Neil M Davies; Michael V Holmes; George Davey Smith
Journal:  BMJ       Date:  2018-07-12
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