A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure.

Authors:
Yun Ju Sung Lisa de Las Fuentes Thomas W Winkler Daniel I Chasman Amy R Bentley Aldi T Kraja Ioanna Ntalla Helen R Warren Xiuqing Guo Karen Schwander Alisa K Manning Michael R Brown Hugues Aschard Mary F Feitosa Nora Franceschini Yingchang Lu Ching-Yu Cheng Xueling Sim Dina Vojinovic Jonathan Marten Solomon K Musani Tuomas O Kilpeläinen Melissa A Richard Stella Aslibekyan Traci M Bartz Rajkumar Dorajoo Changwei Li Yongmei Liu Tuomo Rankinen Albert Vernon Smith Salman M Tajuddin Bamidele O Tayo Wei Zhao Yanhua Zhou Nana Matoba Tamar Sofer Maris Alver Marzyeh Amini Mathilde Boissel Jin Fang Chai Xu Chen Jasmin Divers Ilaria Gandin Chuan Gao Franco Giulianini Anuj Goel Sarah E Harris Fernando P Hartwig Meian He Andrea R V R Horimoto Fang-Chi Hsu Anne U Jackson Candace M Kammerer Anuradhani Kasturiratne Pirjo Komulainen Brigitte Kühnel Karin Leander Wen-Jane Lee Keng-Hung Lin Jian'an Luan Leo-Pekka Lyytikäinen Colin A McKenzie Christopher P Nelson Raymond Noordam Robert A Scott Wayne H H Sheu Alena Stančáková Fumihiko Takeuchi Peter J van der Most Tibor V Varga Robert J Waken Heming Wang Yajuan Wang Erin B Ware Stefan Weiss Wanqing Wen Lisa R Yanek Weihua Zhang Jing Hua Zhao Saima Afaq Tamuno Alfred Najaf Amin Dan E Arking Tin Aung R Graham Barr Lawrence F Bielak Eric Boerwinkle Erwin P Bottinger Peter S Braund Jennifer A Brody Ulrich Broeckel Brian Cade Archie Campbell Mickaël Canouil Aravinda Chakravarti Massimiliano Cocca Francis S Collins John M Connell Renée de Mutsert H Janaka de Silva Marcus Dörr Qing Duan Charles B Eaton Georg Ehret Evangelos Evangelou Jessica D Faul Nita G Forouhi Oscar H Franco Yechiel Friedlander He Gao Bruna Gigante C Charles Gu Preeti Gupta Saskia P Hagenaars Tamara B Harris Jiang He Sami Heikkinen Chew-Kiat Heng Albert Hofman Barbara V Howard Steven C Hunt Marguerite R Irvin Yucheng Jia Tomohiro Katsuya Joel Kaufman Nicola D Kerrison Chiea Chuen Khor Woon-Puay Koh Heikki A Koistinen Charles B Kooperberg Jose E Krieger Michiaki Kubo Zoltan Kutalik Johanna Kuusisto Timo A Lakka Carl D Langefeld Claudia Langenberg Lenore J Launer Joseph H Lee Benjamin Lehne Daniel Levy Cora E Lewis Yize Li Sing Hui Lim Ching-Ti Liu Jianjun Liu Jingmin Liu Yeheng Liu Marie Loh Kurt K Lohman Tin Louie Reedik Mägi Koichi Matsuda Thomas Meitinger Andres Metspalu Lili Milani Yukihide Momozawa Thomas H Mosley Mike A Nalls Ubaydah Nasri Jeff R O'Connell Adesola Ogunniyi Walter R Palmas Nicholette D Palmer James S Pankow Nancy L Pedersen Annette Peters Patricia A Peyser Ozren Polasek David Porteous Olli T Raitakari Frida Renström Treva K Rice Paul M Ridker Antonietta Robino Jennifer G Robinson Lynda M Rose Igor Rudan Charumathi Sabanayagam Babatunde L Salako Kevin Sandow Carsten O Schmidt Pamela J Schreiner William R Scott Peter Sever Mario Sims Colleen M Sitlani Blair H Smith Jennifer A Smith Harold Snieder John M Starr Konstantin Strauch Hua Tang Kent D Taylor Yik Ying Teo Yih Chung Tham André G Uitterlinden Melanie Waldenberger Lihua Wang Ya Xing Wang Wen Bin Wei Gregory Wilson Mary K Wojczynski Yong-Bing Xiang Jie Yao Jian-Min Yuan Alan B Zonderman Diane M Becker Michael Boehnke Donald W Bowden John C Chambers Yii-Der Ida Chen David R Weir Ulf de Faire Ian J Deary Tõnu Esko Martin Farrall Terrence Forrester Barry I Freedman Philippe Froguel Paolo Gasparini Christian Gieger Bernardo Lessa Horta Yi-Jen Hung Jost Bruno Jonas Norihiro Kato Jaspal S Kooner Markku Laakso Terho Lehtimäki Kae-Woei Liang Patrik K E Magnusson Albertine J Oldehinkel Alexandre C Pereira Thomas Perls Rainer Rauramaa Susan Redline Rainer Rettig Nilesh J Samani James Scott Xiao-Ou Shu Pim van der Harst Lynne E Wagenknecht Nicholas J Wareham Hugh Watkins Ananda R Wickremasinghe Tangchun Wu Yoichiro Kamatani Cathy C Laurie Claude Bouchard Richard S Cooper Michele K Evans Vilmundur Gudnason James Hixson Sharon L R Kardia Stephen B Kritchevsky Bruce M Psaty Rob M van Dam Donna K Arnett Dennis O Mook-Kanamori Myriam Fornage Ervin R Fox Caroline Hayward Cornelia M van Duijn E Shyong Tai Tien Yin Wong Ruth J F Loos Alex P Reiner Charles N Rotimi Laura J Bierut Xiaofeng Zhu L Adrienne Cupples Michael A Province Jerome I Rotter Paul W Franks Kenneth Rice Paul Elliott Mark J Caulfield W James Gauderman Patricia B Munroe Dabeeru C Rao Alanna C Morrison

Hum Mol Genet 2019 Apr 10. Epub 2019 Apr 10.

Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.

Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene-smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene-smoking interaction analysis and 38 were newly identified (P < 5 × 10-8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.

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https://academic.oup.com/hmg/advance-article/doi/10.1093/hmg
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http://dx.doi.org/10.1093/hmg/ddz070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6644157PMC
April 2019
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