Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci - Institut Pasteur Access content directly
Journal Articles Molecular Psychiatry Year : 2020

Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci

Lisa de Las Fuentes (1) , Yun Ju Sung (1) , Raymond Noordam (2) , Thomas Winkler (3) , Mary Feitosa (4) , Karen Schwander (4) , Amy Bentley (5) , Michael Brown , Xiuqing Guo (6) , Alisa Manning (7) , Daniel Chasman , Hugues Aschard (8, 9) , Traci Bartz , Lawrence Bielak , Archie Campbell , Ching-Yu Cheng , Rajkumar Dorajoo , Fernando Hartwig , A. Horimoto , Changwei Li , Ruifang Li-Gao , Yongmei Liu , Jonathan Marten , Solomon Musani , Ioanna Ntalla , Tuomo Rankinen , Melissa Richard , Xueling Sim , Albert Smith , Salman Tajuddin , Bamidele Tayo , Dina Vojinovic , Helen Warren , Deng Xuan , Maris Alver , Mathilde Boissel (10) , Jin-Fang Chai , Xu Chen , Kaare Christensen , Jasmin Divers , Evangelos Evangelou , Chuan Gao , Giorgia Girotto , Sarah Harris , Meian He , Fang-Chi Hsu , Brigitte Kühnel , Federica Laguzzi , Xiaoyin Li , Leo-Pekka Lyytikäinen , Ilja Nolte , Alaitz Poveda , Rainer Rauramaa , Muhammad Riaz , Rico Rueedi , Xiao-Ou Shu , Harold Snieder , Tamar Sofer , Fumihiko Takeuchi , Niek Verweij , Erin Ware , Stefan Weiss , Lisa Yanek , Najaf Amin , Dan Arking , Donna Arnett , Sven Bergmann , Eric Boerwinkle , Jennifer Brody , Ulrich Broeckel , Marco Brumat , Gregory Burke , Claudia Cabrera , Mickaël Canouil , Miao Li Chee , Yii-Der Ida Chen , Massimiliano Cocca , John Connell , H Janaka de Silva , Paul de Vries , Gudny Eiriksdottir , Jessica Faul , Virginia Fisher , Terrence Forrester , Ervin Fox , Yechiel Friedlander , He Gao , Bruna Gigante , Franco Giulianini , Chi Charles Gu , Dongfeng Gu , Tamara Harris , Jiang He , Sami Heikkinen , Chew-Kiat Heng , Steven Hunt , M Arfan Ikram , Marguerite Irvin , Mika Kähönen , Maryam Kavousi , Chiea Chuen Khor , Tuomas Kilpeläinen , Woon-Puay Koh , Pirjo Komulainen , Aldi Kraja , J. Krieger , Carl Langefeld , Yize Li , Jingjing Liang , David Liewald , Ching-Ti Liu , Jianjun Liu , Kurt Lohman , Reedik Mägi , Colin Mckenzie , Thomas Meitinger , Andres Metspalu , Yuri Milaneschi , Lili Milani , Dennis Mook-Kanamori , Mike Nalls , Christopher Nelson , Jill Norris , Jeff O'Connell , Adesola Ogunniyi , Sandosh Padmanabhan , Nicholette Palmer , Nancy Pedersen , Thomas Perls , Annette Peters , Astrid Petersmann , Patricia Peyser , Ozren Polasek , David Porteous , Leslie Raffel , Treva Rice , Jerome Rotter , Igor Rudan , Oscar-Leonel Rueda-Ochoa , Charumathi Sabanayagam , Babatunde Salako , Pamela Schreiner , James Shikany , Stephen Sidney , Mario Sims , Colleen Sitlani , Jennifer Smith , John Starr , Konstantin Strauch , Morris Swertz , Alexander Teumer , Yih Chung Tham , André Uitterlinden , Dhananjay Vaidya , M Yldau van Der Ende , Melanie Waldenberger , Lihua Wang , Ya-Xing Wang , Wen-Bin Wei , David Weir , Wanqing Wen , Jie Yao , Bing Yu , Caizheng Yu , Jian-Min Yuan , Wei Zhao , Alan Zonderman , Diane Becker , Donald Bowden , Ian Deary , Marcus Dörr , Tõnu Esko , Barry Freedman , Philippe Froguel , Paolo Gasparini , Christian Gieger , Jost Bruno Jonas , Candace Kammerer , Norihiro Kato , Timo Lakka , Karin Leander , Terho Lehtimäki , Patrik Magnusson , Pedro Marques-Vidal , Brenda Penninx , Nilesh Samani , Pim van Der Harst , Lynne Wagenknecht , Tangchun Wu , Wei Zheng , Xiaofeng Zhu , Claude Bouchard , Richard Cooper , Adolfo Correa , Michele Evans , Vilmundur Gudnason , Caroline Hayward , Bernardo Horta , Tanika Kelly , Stephen Kritchevsky , Daniel Levy , Walter Palmas , A. Pereira , Michael Province , Bruce Psaty , Paul Ridker , Charles Rotimi , E Shyong Tai , Rob van Dam , Cornelia van Duijn , Tien Yin Wong , Kenneth Rice , W James Gauderman , Alanna Morrison , Kari North , Sharon Kardia , Mark Caulfield , Paul Elliott , Patricia Munroe , Paul Franks , Dabeeru Rao , Myriam Fornage (11)
Michael Brown
  • Function : Author
Daniel Chasman
  • Function : Author
Traci Bartz
  • Function : Author
Lawrence Bielak
  • Function : Author
Archie Campbell
  • Function : Author
Ching-Yu Cheng
  • Function : Author
Rajkumar Dorajoo
Fernando Hartwig
  • Function : Author
A. Horimoto
  • Function : Author
Changwei Li
  • Function : Author
Ruifang Li-Gao
  • Function : Author
Yongmei Liu
  • Function : Author
Jonathan Marten
  • Function : Author
Solomon Musani
  • Function : Author
Ioanna Ntalla
  • Function : Author
Tuomo Rankinen
  • Function : Author
Melissa Richard
  • Function : Author
Xueling Sim
  • Function : Author
Albert Smith
  • Function : Author
Salman Tajuddin
  • Function : Author
Bamidele Tayo
  • Function : Author
Dina Vojinovic
  • Function : Author
Helen Warren
  • Function : Author
Deng Xuan
  • Function : Author
Maris Alver
  • Function : Author
Jin-Fang Chai
  • Function : Author
Xu Chen
  • Function : Author
Kaare Christensen
  • Function : Author
Jasmin Divers
  • Function : Author
Evangelos Evangelou
  • Function : Author
Chuan Gao
  • Function : Author
Giorgia Girotto
  • Function : Author
Sarah Harris
Meian He
  • Function : Author
Fang-Chi Hsu
  • Function : Author
Brigitte Kühnel
  • Function : Author
Federica Laguzzi
  • Function : Author
Xiaoyin Li
  • Function : Author
Leo-Pekka Lyytikäinen
  • Function : Author
Ilja Nolte
  • Function : Author
Alaitz Poveda
  • Function : Author
Rainer Rauramaa
  • Function : Author
Muhammad Riaz
  • Function : Author
Rico Rueedi
  • Function : Author
Xiao-Ou Shu
  • Function : Author
Harold Snieder
  • Function : Author
Tamar Sofer
  • Function : Author
Fumihiko Takeuchi
  • Function : Author
Niek Verweij
  • Function : Author
Erin Ware
  • Function : Author
Stefan Weiss
  • Function : Author
Lisa Yanek
  • Function : Author
Najaf Amin
  • Function : Author
Dan Arking
  • Function : Author
Donna Arnett
  • Function : Author
Sven Bergmann
  • Function : Author
Eric Boerwinkle
  • Function : Author
Jennifer Brody
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Ulrich Broeckel
  • Function : Author
Marco Brumat
  • Function : Author
Gregory Burke
  • Function : Author
Claudia Cabrera
  • Function : Author
Mickaël Canouil
Miao Li Chee
  • Function : Author
Yii-Der Ida Chen
  • Function : Author
Massimiliano Cocca
  • Function : Author
John Connell
  • Function : Author
H Janaka de Silva
  • Function : Author
Paul de Vries
  • Function : Author
Gudny Eiriksdottir
  • Function : Author
Jessica Faul
  • Function : Author
Virginia Fisher
  • Function : Author
Terrence Forrester
  • Function : Author
Ervin Fox
  • Function : Author
Yechiel Friedlander
  • Function : Author
He Gao
  • Function : Author
Bruna Gigante
  • Function : Author
Franco Giulianini
  • Function : Author
Chi Charles Gu
  • Function : Author
Dongfeng Gu
  • Function : Author
Tamara Harris
  • Function : Author
Jiang He
  • Function : Author
Sami Heikkinen
  • Function : Author
Chew-Kiat Heng
  • Function : Author
Steven Hunt
  • Function : Author
M Arfan Ikram
  • Function : Author
Marguerite Irvin
  • Function : Author
Mika Kähönen
Maryam Kavousi
  • Function : Author
Chiea Chuen Khor
Tuomas Kilpeläinen
  • Function : Author
Woon-Puay Koh
  • Function : Author
Pirjo Komulainen
  • Function : Author
Aldi Kraja
  • Function : Author
J. Krieger
  • Function : Author
Carl Langefeld
  • Function : Author
Yize Li
  • Function : Author
Jingjing Liang
David Liewald
  • Function : Author
Ching-Ti Liu
  • Function : Author
Jianjun Liu
Kurt Lohman
  • Function : Author
Reedik Mägi
  • Function : Author
Colin Mckenzie
  • Function : Author
Thomas Meitinger
  • Function : Author
Andres Metspalu
  • Function : Author
Yuri Milaneschi
  • Function : Author
Lili Milani
  • Function : Author
Dennis Mook-Kanamori
  • Function : Author
Mike Nalls
  • Function : Author
Christopher Nelson
  • Function : Author
Jill Norris
  • Function : Author
Jeff O'Connell
  • Function : Author
Adesola Ogunniyi
  • Function : Author
Sandosh Padmanabhan
  • Function : Author
Nicholette Palmer
  • Function : Author
Nancy Pedersen
  • Function : Author
Thomas Perls
  • Function : Author
Annette Peters
Astrid Petersmann
  • Function : Author
Patricia Peyser
  • Function : Author
Ozren Polasek
  • Function : Author
David Porteous
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Leslie Raffel
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Treva Rice
  • Function : Author
Jerome Rotter
  • Function : Author
Igor Rudan
  • Function : Author
Oscar-Leonel Rueda-Ochoa
  • Function : Author
Charumathi Sabanayagam
  • Function : Author
Babatunde Salako
  • Function : Author
Pamela Schreiner
  • Function : Author
James Shikany
  • Function : Author
Stephen Sidney
  • Function : Author
Mario Sims
  • Function : Author
Colleen Sitlani
  • Function : Author
Jennifer Smith
  • Function : Author
John Starr
  • Function : Author
Konstantin Strauch
  • Function : Author
Morris Swertz
  • Function : Author
Alexander Teumer
  • Function : Author
Yih Chung Tham
  • Function : Author
André Uitterlinden
  • Function : Author
Dhananjay Vaidya
  • Function : Author
M Yldau van Der Ende
  • Function : Author
Melanie Waldenberger
  • Function : Author
Lihua Wang
  • Function : Author
Ya-Xing Wang
  • Function : Author
Wen-Bin Wei
  • Function : Author
David Weir
  • Function : Author
Wanqing Wen
  • Function : Author
Jie Yao
  • Function : Author
Bing Yu
Caizheng Yu
  • Function : Author
Jian-Min Yuan
  • Function : Author
Wei Zhao
  • Function : Author
Alan Zonderman
  • Function : Author
Diane Becker
  • Function : Author
Donald Bowden
  • Function : Author
Ian Deary
  • Function : Author
Marcus Dörr
  • Function : Author
Tõnu Esko
  • Function : Author
Barry Freedman
  • Function : Author
Philippe Froguel
  • Function : Author
Paolo Gasparini
  • Function : Author
Christian Gieger
  • Function : Author
Jost Bruno Jonas
  • Function : Author
Candace Kammerer
  • Function : Author
Norihiro Kato
  • Function : Author
Timo Lakka
  • Function : Author
Karin Leander
Terho Lehtimäki
  • Function : Author
Patrik Magnusson
  • Function : Author
Pedro Marques-Vidal
  • Function : Author
Brenda Penninx
  • Function : Author
Nilesh Samani
Pim van Der Harst
  • Function : Author
Lynne Wagenknecht
  • Function : Author
Tangchun Wu
  • Function : Author
Wei Zheng
Xiaofeng Zhu
  • Function : Author
Claude Bouchard
  • Function : Author
Richard Cooper
Adolfo Correa
  • Function : Author
Michele Evans
  • Function : Author
Vilmundur Gudnason
  • Function : Author
Caroline Hayward
  • Function : Author
Bernardo Horta
  • Function : Author
Tanika Kelly
  • Function : Author
Stephen Kritchevsky
  • Function : Author
Daniel Levy
  • Function : Author
Walter Palmas
  • Function : Author
A. Pereira
  • Function : Author
Michael Province
  • Function : Author
Bruce Psaty
  • Function : Author
Paul Ridker
  • Function : Author
Charles Rotimi
  • Function : Author
E Shyong Tai
  • Function : Author
Rob van Dam
  • Function : Author
Cornelia van Duijn
  • Function : Author
Tien Yin Wong
  • Function : Author
Kenneth Rice
  • Function : Author
W James Gauderman
  • Function : Author
Alanna Morrison
  • Function : Author
Kari North
  • Function : Author
Sharon Kardia
  • Function : Author
Mark Caulfield
  • Function : Author
Paul Elliott
Patricia Munroe
  • Function : Author
Paul Franks
  • Function : Author
Dabeeru Rao
  • Function : Author

Abstract

Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.

Dates and versions

pasteur-03278567 , version 1 (05-07-2021)

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Cite

Lisa de Las Fuentes, Yun Ju Sung, Raymond Noordam, Thomas Winkler, Mary Feitosa, et al.. Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci. Molecular Psychiatry, 2020, ⟨10.1038/s41380-020-0719-3⟩. ⟨pasteur-03278567⟩
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