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Journal Articles Molecular Psychiatry Year : 2020

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

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

Identifiers

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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