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Journal Articles Human Molecular Genetics Year : 2019

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

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Lisa de Las Fuentes
  • Function : Author
Thomas Winkler
  • Function : Author
Amy Bentley
  • Function : Author
Aldi Kraja
  • Function : Author
Karen Schwander
  • Function : Author
Alisa Manning
  • Function : Author
Michael Brown
  • Function : Author
Mary Feitosa
  • Function : Author
Nora Franceschini
  • Function : Author
Yingchang Lu
  • Function : Author
Ching-Yu Cheng
  • Function : Author
Xueling Sim
  • Function : Author
Dina Vojinovic
  • Function : Author
Jonathan Marten
  • Function : Author
Solomon Musani
  • Function : Author
Tuomas Kilpeläinen
  • Function : Author
Melissa Richard
  • Function : Author
Stella Aslibekyan
  • Function : Author
Traci Bartz
  • Function : Author
Rajkumar Dorajoo
Changwei Li
  • Function : Author
Yongmei Liu
  • Function : Author
Tuomo Rankinen
  • Function : Author
Albert Vernon Smith
  • Function : Author
Salman Tajuddin
  • Function : Author
Bamidele Tayo
  • Function : Author
Wei Zhao
  • Function : Author
Yanhua Zhou
  • Function : Author
Nana Matoba
  • Function : Author
Tamar Sofer
  • Function : Author
Maris Alver
  • Function : Author
Marzyeh Amini
  • Function : Author
Mathilde Boissel
  • Function : Author
Jin Fang Chai
  • Function : Author
Xu Chen
  • Function : Author
Jasmin Divers
  • Function : Author
Ilaria Gandin
  • Function : Author
Chuan Gao
  • Function : Author
Franco Giulianini
  • Function : Author
Anuj Goel
  • Function : Author
Sarah Harris
Fernando Hartwig
  • Function : Author
Meian He
  • Function : Author
Andrea Horimoto
  • Function : Author
Fang-Chi Hsu
  • Function : Author
Anne Jackson
  • Function : Author
Candace Kammerer
  • Function : Author
Anuradhani Kasturiratne
  • Function : Author
Pirjo Komulainen
  • Function : Author
Brigitte Kühnel
  • Function : Author
Karin Leander
Wen-Jane Lee
  • Function : Author
Keng-Hung Lin
  • Function : Author
Jian'An Luan
  • Function : Author
Leo-Pekka Lyytikäinen
  • Function : Author
Colin Mckenzie
  • Function : Author
Christopher Nelson
  • Function : Author
Raymond Noordam
  • Function : Author
Robert Scott
  • Function : Author
Wayne Sheu
  • Function : Author
Alena Stančáková
  • Function : Author
Fumihiko Takeuchi
  • Function : Author
Peter van Der Most
  • Function : Author
Tibor Varga
Robert Waken
  • Function : Author
Heming Wang
  • Function : Author
Yajuan Wang
  • Function : Author
Erin Ware
  • Function : Author
Stefan Weiss
  • Function : Author
Wanqing Wen
  • Function : Author
Lisa Yanek
  • Function : Author
Weihua Zhang
  • Function : Author
Jing Hua Zhao
  • Function : Author
Saima Afaq
  • Function : Author
Tamuno Alfred
  • Function : Author
Najaf Amin
  • Function : Author
Dan Arking
  • Function : Author
Tin Aung
  • Function : Author
R Graham Barr
  • Function : Author
Lawrence Bielak
  • Function : Author
Eric Boerwinkle
  • Function : Author
Erwin Bottinger
  • Function : Author
Peter Braund
  • Function : Author
Jennifer Brody
  • Function : Author
Ulrich Broeckel
  • Function : Author
Brian Cade
  • Function : Author
Archie Campbell
  • Function : Author
Aravinda Chakravarti
  • Function : Author
Massimiliano Cocca
  • Function : Author
Francis Collins
  • Function : Author
John Connell
  • Function : Author
Renée de Mutsert
  • Function : Author
H Janaka de Silva
  • Function : Author
Marcus Dörr
  • Function : Author
Qing Duan
  • Function : Author
Charles Eaton
  • Function : Author
Georg Ehret
  • Function : Author
Evangelos Evangelou
  • Function : Author
Jessica Faul
  • Function : Author
Nita Forouhi
  • Function : Author
Oscar Franco
  • Function : Author
Yechiel Friedlander
  • Function : Author
He Gao
  • Function : Author
Bruna Gigante
  • Function : Author
C Charles Gu
  • Function : Author
Preeti Gupta
  • Function : Author
Saskia Hagenaars
  • Function : Author
Tamara Harris
  • Function : Author
Jiang He
  • Function : Author
Sami Heikkinen
  • Function : Author
Chew-Kiat Heng
  • Function : Author
Albert Hofman
  • Function : Author
Barbara Howard
  • Function : Author
Steven Hunt
  • Function : Author
Marguerite Irvin
  • Function : Author
Yucheng Jia
  • Function : Author
Tomohiro Katsuya
  • Function : Author
Joel Kaufman
  • Function : Author
Nicola Kerrison
  • Function : Author
Chiea Chuen Khor
Woon-Puay Koh
  • Function : Author
Heikki Koistinen
  • Function : Author
Charles Kooperberg
  • Function : Author
Jose Krieger
  • Function : Author
Michiaki Kubo
  • Function : Author
Zoltan Kutalik
  • Function : Author
Johanna Kuusisto
  • Function : Author
Timo Lakka
  • Function : Author
Carl Langefeld
  • Function : Author
Claudia Langenberg
  • Function : Author
Lenore Launer
  • Function : Author
Joseph Lee
  • Function : Author
Benjamin Lehne
  • Function : Author
Daniel Levy
  • Function : Author
Cora Lewis
  • Function : Author
Yize Li
  • Function : Author
Sing Hui Lim
  • Function : Author
Ching-Ti Liu
  • Function : Author
Jianjun Liu
Jingmin Liu
  • Function : Author
Yeheng Liu
  • Function : Author
Marie Loh
  • Function : Author
Kurt Lohman
  • Function : Author
Tin Louie
  • Function : Author
Reedik Mägi
  • Function : Author
Koichi Matsuda
  • Function : Author
Thomas Meitinger
  • Function : Author
Andres Metspalu
  • Function : Author
Lili Milani
  • Function : Author
Yukihide Momozawa
  • Function : Author
Thomas Mosley
  • Function : Author
Mike Nalls
  • Function : Author
Ubaydah Nasri
  • Function : Author
Jeff O'Connell
  • Function : Author
Adesola Ogunniyi
  • Function : Author
Walter Palmas
  • Function : Author
Nicholette Palmer
  • Function : Author
James Pankow
  • Function : Author
Nancy Pedersen
  • Function : Author
Annette Peters
Patricia Peyser
  • Function : Author
Ozren Polasek
  • Function : Author
David Porteous
  • Function : Author
Olli Raitakari
  • Function : Author
Frida Renström
  • Function : Author
Treva Rice
  • Function : Author
Paul Ridker
  • Function : Author
Antonietta Robino
  • Function : Author
Jennifer Robinson
  • Function : Author
Lynda Rose
  • Function : Author
Igor Rudan
  • Function : Author
Charumathi Sabanayagam
  • Function : Author
Babatunde Salako
  • Function : Author
Kevin Sandow
  • Function : Author
Carsten Schmidt
  • Function : Author
Pamela Schreiner
  • Function : Author
William Scott
  • Function : Author
Peter Sever
Mario Sims
  • Function : Author
Colleen Sitlani
  • Function : Author
Blair Smith
  • Function : Author
Jennifer Smith
  • Function : Author
Harold Snieder
  • Function : Author
John Starr
  • Function : Author
Konstantin Strauch
  • Function : Author
Hua Tang
  • Function : Author
Kent Taylor
  • Function : Author
Yik Ying Teo
  • Function : Author
Yih Chung Tham
  • Function : Author
André Uitterlinden
  • Function : Author
Melanie Waldenberger
  • Function : Author
Lihua Wang
  • Function : Author
Ya Xing Wang
  • Function : Author
Wen Bin Wei
  • Function : Author
Gregory Wilson
  • Function : Author
Mary Wojczynski
  • Function : Author
Yong-Bing Xiang
  • Function : Author
Jie Yao
  • Function : Author
Jian-Min Yuan
  • Function : Author
Alan Zonderman
  • Function : Author
Diane Becker
  • Function : Author
Michael Boehnke
  • Function : Author
Donald Bowden
  • Function : Author
John Chambers
  • Function : Author
Yii-Der Ida Chen
  • Function : Author
David Weir
  • Function : Author
Ulf de Faire
  • Function : Author
Ian Deary
  • Function : Author
Tõnu Esko
  • Function : Author
Martin Farrall
  • Function : Author
Terrence Forrester
  • Function : Author
Barry Freedman
  • Function : Author
Philippe Froguel
  • Function : Author
Paolo Gasparini
  • Function : Author
Christian Gieger
  • Function : Author
Bernardo Lessa Horta
  • Function : Author
Yi-Jen Hung
  • Function : Author
Jost Bruno Jonas
  • Function : Author
Norihiro Kato
  • Function : Author
Jaspal Kooner
  • Function : Author
Markku Laakso
  • Function : Author
Terho Lehtimäki
  • Function : Author
Kae-Woei Liang
  • Function : Author
Patrik Magnusson
  • Function : Author
Albertine Oldehinkel
  • Function : Author
Alexandre Pereira
Thomas Perls
  • Function : Author
Rainer Rauramaa
  • Function : Author
Susan Redline
  • Function : Author
Rainer Rettig
  • Function : Author
Nilesh Samani
James Scott
Xiao-Ou Shu
  • Function : Author
Pim van Der Harst
  • Function : Author
Lynne Wagenknecht
  • Function : Author
Nicholas Wareham
  • Function : Author
Hugh Watkins
  • Function : Author
Ananda Wickremasinghe
  • Function : Author
Tangchun Wu
  • Function : Author
Yoichiro Kamatani
  • Function : Author
Cathy Laurie
  • Function : Author
Claude Bouchard
  • Function : Author
Richard Cooper
Michele Evans
  • Function : Author
Vilmundur Gudnason
  • Function : Author
James Hixson
  • Function : Author
Sharon Kardia
  • Function : Author
Stephen Kritchevsky
  • Function : Author
Bruce Psaty
  • Function : Author
Rob van Dam
  • Function : Author
Donna Arnett
  • Function : Author
Dennis Mook-Kanamori
  • Function : Author
Myriam Fornage
  • Function : Author
Ervin Fox
  • Function : Author
Caroline Hayward
  • Function : Author
Cornelia van Duijn
  • Function : Author
E Shyong Tai
  • Function : Author
Tien Yin Wong
  • Function : Author
Ruth Loos
  • Function : Author
Alex Reiner
  • Function : Author
Charles Rotimi
  • Function : Author
Laura Bierut
  • Function : Author
Xiaofeng Zhu
  • Function : Author
L Adrienne Cupples
  • Function : Author
Michael Province
  • Function : Author
Jerome Rotter
  • Function : Author
Paul Franks
  • Function : Author
Kenneth Rice
  • Function : Author
Paul Elliott
Mark Caulfield
  • Function : Author
W James Gauderman
  • Function : Author
Patricia Munroe
  • Function : Author
Dabeeru Rao
  • Function : Author

Abstract

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.

Dates and versions

pasteur-03278563 , version 1 (05-07-2021)

Identifiers

Cite

Yun Ju Sung, Lisa de Las Fuentes, Thomas Winkler, Daniel Chasman, Amy Bentley, et al.. A multi-ancestry genome-wide study incorporating gene–smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure. Human Molecular Genetics, 2019, 28 (15), pp.2615-2633. ⟨10.1093/hmg/ddz070⟩. ⟨pasteur-03278563⟩
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