TY - JOUR
T1 - Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci.
JF - Mol Psychiatry
Y1 - 2021
A1 - de Las Fuentes, Lisa
A1 - Yun Ju Sung
A1 - Noordam, Raymond
A1 - Thomas W Winkler
A1 - Feitosa, Mary F
A1 - Schwander, Karen
A1 - Bentley, Amy R
A1 - Brown, Michael R
A1 - Guo, Xiuqing
A1 - Alisa Manning
A1 - Daniel I Chasman
A1 - Aschard, Hugues
A1 - Traci M Bartz
A1 - Bielak, Lawrence F
A1 - Campbell, Archie
A1 - Cheng, Ching-Yu
A1 - Dorajoo, Rajkumar
A1 - Hartwig, Fernando P
A1 - Horimoto, A R V R
A1 - Li, Changwei
A1 - Li-Gao, Ruifang
A1 - Liu, Yongmei
A1 - Marten, Jonathan
A1 - Musani, Solomon K
A1 - Ntalla, Ioanna
A1 - Rankinen, Tuomo
A1 - Melissa Richard
A1 - Sim, Xueling
A1 - Smith, Albert V
A1 - Tajuddin, Salman M
A1 - Bamidele O Tayo
A1 - Vojinovic, Dina
A1 - Warren, Helen R
A1 - Xuan, Deng
A1 - Alver, Maris
A1 - Boissel, Mathilde
A1 - Jin-Fang Chai
A1 - Chen, Xu
A1 - Christensen, Kaare
A1 - Divers, Jasmin
A1 - Evangelou, Evangelos
A1 - Gao, Chuan
A1 - Giorgia G Girotto
A1 - Sarah E Harris
A1 - He, Meian
A1 - Hsu, Fang-Chi
A1 - Kühnel, Brigitte
A1 - Laguzzi, Federica
A1 - Li, Xiaoyin
A1 - Lyytikäinen, Leo-Pekka
A1 - Ilja M Nolte
A1 - Poveda, Alaitz
A1 - Rauramaa, Rainer
A1 - Riaz, Muhammad
A1 - Rueedi, Rico
A1 - Shu, Xiao-Ou
A1 - Snieder, Harold
A1 - Sofer, Tamar
A1 - Takeuchi, Fumihiko
A1 - Verweij, Niek
A1 - Erin B Ware
A1 - Weiss, Stefan
A1 - Yanek, Lisa R
A1 - Amin, Najaf
A1 - Dan E Arking
A1 - Donna K Arnett
A1 - Bergmann, Sven
A1 - Boerwinkle, Eric
A1 - Brody, Jennifer A
A1 - Broeckel, Ulrich
A1 - Brumat, Marco
A1 - Burke, Gregory
A1 - Cabrera, Claudia P
A1 - Canouil, Mickaël
A1 - Chee, Miao Li
A1 - Chen, Yii-Der Ida
A1 - Cocca, Massimiliano
A1 - Connell, John
A1 - de Silva, H Janaka
A1 - de Vries, Paul S
A1 - Eiriksdottir, Gudny
A1 - Jessica Faul
A1 - Fisher, Virginia
A1 - Forrester, Terrence
A1 - Fox, Ervin F
A1 - Friedlander, Yechiel
A1 - Gao, He
A1 - Gigante, Bruna
A1 - Giulianini, Franco
A1 - Gu, Chi Charles
A1 - Gu, Dongfeng
A1 - Tamara B Harris
A1 - He, Jiang
A1 - Heikkinen, Sami
A1 - Heng, Chew-Kiat
A1 - Hunt, Steven
A1 - Ikram, M Arfan
A1 - Irvin, Marguerite R
A1 - Kähönen, Mika
A1 - Kavousi, Maryam
A1 - Khor, Chiea Chuen
A1 - Kilpeläinen, Tuomas O
A1 - Koh, Woon-Puay
A1 - Komulainen, Pirjo
A1 - Kraja, Aldi T
A1 - Krieger, J E
A1 - Langefeld, Carl D
A1 - Li, Yize
A1 - Liang, Jingjing
A1 - David C Liewald
A1 - Liu, Ching-Ti
A1 - Liu, Jianjun
A1 - Kurt Lohman
A1 - Mägi, Reedik
A1 - McKenzie, Colin A
A1 - Meitinger, Thomas
A1 - Andres Metspalu
A1 - Milaneschi, Yuri
A1 - Lili Milani
A1 - Dennis O Mook-Kanamori
A1 - Michael A Nalls
A1 - Nelson, Christopher P
A1 - Norris, Jill M
A1 - Jeff O'Connell
A1 - Ogunniyi, Adesola
A1 - Padmanabhan, Sandosh
A1 - Palmer, Nicholette D
A1 - Nancy L Pedersen
A1 - Thomas T Perls
A1 - Peters, Annette
A1 - Petersmann, Astrid
A1 - Peyser, Patricia A
A1 - Polasek, Ozren
A1 - David J Porteous
A1 - Raffel, Leslie J
A1 - Rice, Treva K
A1 - Rotter, Jerome I
A1 - Rudan, Igor
A1 - Rueda-Ochoa, Oscar-Leonel
A1 - Sabanayagam, Charumathi
A1 - Babatunde Salako
A1 - Schreiner, Pamela J
A1 - Shikany, James M
A1 - Stephen Sidney
A1 - Sims, Mario
A1 - Sitlani, Colleen M
A1 - Smith, Jennifer A
A1 - John M Starr
A1 - Strauch, Konstantin
A1 - Swertz, Morris A
A1 - Teumer, Alexander
A1 - Tham, Yih Chung
A1 - André G Uitterlinden
A1 - Vaidya, Dhananjay
A1 - van der Ende, M Yldau
A1 - Waldenberger, Melanie
A1 - Wang, Lihua
A1 - Wang, Ya-Xing
A1 - Wei, Wen-Bin
A1 - David R Weir
A1 - Wen, Wanqing
A1 - Yao, Jie
A1 - Yu, Bing
A1 - Yu, Caizheng
A1 - Yuan, Jian-Min
A1 - Zhao, Wei
A1 - Alan B Zonderman
A1 - Becker, Diane M
A1 - Bowden, Donald W
A1 - Ian J Deary
A1 - Dörr, Marcus
A1 - Tõnu Esko
A1 - Freedman, Barry I
A1 - Froguel, Philippe
A1 - Paolo P. Gasparini
A1 - Gieger, Christian
A1 - Jost Bruno Jonas
A1 - Kammerer, Candace M
A1 - Kato, Norihiro
A1 - Lakka, Timo A
A1 - Leander, Karin
A1 - Lehtimäki, Terho
A1 - Patrik K E Magnusson
A1 - Marques-Vidal, Pedro
A1 - Brenda W J H Penninx
A1 - Nilesh J Samani
A1 - van der Harst, Pim
A1 - Wagenknecht, Lynne E
A1 - Wu, Tangchun
A1 - Zheng, Wei
A1 - Zhu, Xiaofeng
A1 - Bouchard, Claude
A1 - Cooper, Richard S
A1 - Correa, Adolfo
A1 - Michele K Evans
A1 - Gudnason, Vilmundur
A1 - Caroline Hayward
A1 - Horta, Bernardo L
A1 - Tanika N Kelly
A1 - Stephen B Kritchevsky
A1 - Levy, Daniel
A1 - Walter R Palmas
A1 - Pereira, A C
A1 - Province, Michael M
A1 - Psaty, Bruce M
A1 - Ridker, Paul M
A1 - Charles N Rotimi
A1 - Tai, E Shyong
A1 - van Dam, Rob M
A1 - Cornelia M van Duijn
A1 - Wong, Tien Yin
A1 - Kenneth Rice
A1 - Gauderman, W James
A1 - Alanna C Morrison
A1 - Kari E North
A1 - Sharon L R Kardia
A1 - Caulfield, Mark J
A1 - Elliott, Paul
A1 - Munroe, Patricia B
A1 - Franks, Paul W
A1 - Rao, Dabeeru C
A1 - Myriam Fornage
KW - Blood pressure
KW - Epistasis, Genetic
KW - Genetic Loci
KW - Genome-Wide Association Study
KW - Humans
KW - Hypertension
KW - Polymorphism, Single Nucleotide
AB - 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). 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.

VL - 26
IS - 6
ER -