A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure.

Authors:
Dr Anubha Mahajan, PhD
Dr Anubha Mahajan, PhD
Wellcome Trust Centre for Human Genetics, University of Oxford
UK
Saima Afaq
Saima Afaq
Institute of Public health and Social Sciences, Khyber medical university Peshawar Pakistan
Dr
Peshawar, KPK | Pakistan
Yun J Sung Thomas W Winkler Lisa de Las Fuentes Amy R Bentley Michael R Brown Aldi T Kraja Karen Schwander Ioanna Ntalla Xiuqing Guo Nora Franceschini Yingchang Lu Ching-Yu Cheng Xueling Sim Dina Vojinovic Jonathan Marten Solomon K Musani Changwei Li Mary F Feitosa Tuomas O Kilpeläinen Melissa A Richard Raymond Noordam Stella Aslibekyan Hugues Aschard Traci M Bartz Rajkumar Dorajoo Yongmei Liu Alisa K Manning Tuomo Rankinen Albert Vernon Smith Salman M Tajuddin Bamidele O Tayo Helen R Warren 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 Pires Hartwig Andrea R V R Horimoto Fang-Chi Hsu Anne U Jackson Mika Kähönen Anuradhani Kasturiratne Brigitte Kühnel Karin Leander Wen-Jane Lee Keng-Hung Lin Jian 'an Luan Colin A McKenzie He Meian Christopher P Nelson Rainer Rauramaa Nicole Schupf Robert A Scott Wayne H H Sheu Alena Stančáková Fumihiko Takeuchi Peter J van der Most Tibor V Varga Heming Wang Yajuan Wang Erin B Ware Stefan Weiss Wanqing Wen Lisa R Yanek Weihua Zhang Jing Hua Zhao Tamuno Alfred Najaf Amin Dan Arking Tin Aung R Graham Barr Lawrence F Bielak Eric Boerwinkle Erwin P Bottinger Peter S Braund Jennifer A Brody Ulrich Broeckel Claudia P Cabrera Brian Cade Yu Caizheng Archie Campbell Mickaël Canouil Aravinda Chakravarti Ganesh Chauhan Kaare Christensen Massimiliano Cocca Francis S Collins John M Connell Renée de Mutsert H Janaka de Silva Stephanie Debette Marcus Dörr Qing Duan Charles B Eaton Georg Ehret Evangelos Evangelou Jessica D Faul Virginia A Fisher Nita G Forouhi Oscar H Franco Yechiel Friedlander He Gao Bruna Gigante Misa Graff C Charles Gu Dongfeng Gu Preeti Gupta Saskia P Hagenaars Tamara B Harris Jiang He Sami Heikkinen Chew-Kiat Heng Makoto Hirata Albert Hofman Barbara V Howard Steven Hunt Marguerite R Irvin Yucheng Jia Roby Joehanes Anne E Justice Tomohiro Katsuya Joel Kaufman Nicola D Kerrison Chiea Chuen Khor Woon-Puay Koh Heikki A Koistinen Pirjo Komulainen Charles Kooperberg Jose E Krieger Michiaki Kubo Johanna Kuusisto Carl D Langefeld Claudia Langenberg Lenore J Launer Benjamin Lehne Cora E Lewis Yize Li Sing Hui Lim Shiow Lin Ching-Ti Liu Jianjun Liu Jingmin Liu Kiang Liu Yeheng Liu Marie Loh Kurt K Lohman Jirong Long Tin Louie Reedik Mägi Thomas Meitinger Andres Metspalu Lili Milani Yukihide Momozawa Andrew P Morris Thomas H Mosley Peter Munson Alison D Murray Mike A Nalls Ubaydah Nasri Jill M Norris Kari North Adesola Ogunniyi Sandosh Padmanabhan Walter R Palmas Nicholette D Palmer James S Pankow Nancy L Pedersen Annette Peters Patricia A Peyser Ozren Polasek 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 Sudha Seshadri Peter Sever Colleen M Sitlani 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 X Wang Wen Bin Wei Christine Williams Gregory Wilson Mary K Wojczynski Jie Yao Jian-Min Yuan Alan B Zonderman Diane M Becker Michael Boehnke Donald W Bowden John C Chambers Yii-Der Ida Chen Ulf de Faire Ian J Deary Tõnu Esko Martin Farrall Terrence Forrester Paul W Franks Barry I Freedman Philippe Froguel Paolo Gasparini Christian Gieger Bernardo Lessa Horta Yi-Jen Hung Jost B Jonas Norihiro Kato Jaspal S Kooner Markku Laakso Terho Lehtimäki Kae-Woei Liang Patrik K E Magnusson Anne B Newman Albertine J Oldehinkel Alexandre C Pereira Susan Redline Rainer Rettig Nilesh J Samani James Scott Xiao-Ou Shu Pim van der Harst Lynne E Wagenknecht Nicholas J Wareham Hugh Watkins David R Weir Ananda R Wickremasinghe Tangchun Wu Wei Zheng Yoichiro Kamatani Cathy C Laurie Claude Bouchard Richard S Cooper Michele K Evans Vilmundur Gudnason Sharon L R Kardia Stephen B Kritchevsky Daniel Levy Jeff R O'Connell Bruce M Psaty Rob M van Dam Mario Sims Donna K Arnett Dennis O Mook-Kanamori Tanika N Kelly Ervin R Fox Caroline Hayward Myriam Fornage Charles N Rotimi Michael A Province Cornelia M van Duijn E Shyong Tai Tien Yin Wong Ruth J F Loos Alex P Reiner Jerome I Rotter Xiaofeng Zhu Laura J Bierut W James Gauderman Mark J Caulfield Paul Elliott Kenneth Rice Patricia B Munroe Alanna C Morrison L Adrienne Cupples Dabeeru C Rao Daniel I Chasman

Am J Hum Genet 2018 03 15;102(3):375-400. Epub 2018 Feb 15.

Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02215, USA. Electronic address:

Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined ∼18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5 × 10) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5 × 10). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling (MSRA, EBF2).

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http://dx.doi.org/10.1016/j.ajhg.2018.01.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985266PMC
March 2018
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