Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41380-020-0719-3
Title: Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci
Authors: de las Fuentes, Lisa
Sung, Yun Ju
Noordam, Raymond
Winkler, Thomas
Feitosa, Mary F
Schwander, Karen
Bentley, Amy R
Brown, Michael R
Guo, Xiuqing
Manning, Alisa
Chasman, Daniel I
Aschard, Hugues
Bartz, Traci M
Bielak, Lawrence F
Campbell, Archie
Cheng, Ching-Yu
Dorajoo, Rajkumar
Hartwig, Fernando P
Horimoto, ARVR
Li, Changwei
Li-Gao, Ruifang
Liu, Yongmei
Marten, Jonathan
Musani, Solomon K
Ntalla, Ioanna
Rankinen, Tuomo
Richard, Melissa
Sim, Xueling 
Smith, Albert V
Tajuddin, Salman M
Tayo, Bamidele O
Vojinovic, Dina
Warren, Helen R
Xuan, Deng
Alver, Maris
Boissel, Mathilde
Chai, Jin-Fang
Chen, Xu
Christensen, Kaare
Divers, Jasmin
Evangelou, Evangelos
Gao, Chuan
Girotto, Giorgia
Harris, Sarah E
He, Meian
Hsu, Fang-Chi
Kuehnel, Brigitte
Laguzzi, Federica
Li, Xiaoyin
Lyytikainen, Leo-Pekka
Nolte, Ilja M
Poveda, Alaitz
Rauramaa, Rainer
Riaz, Muhammad
Rueedi, Rico
Shu, Xiao-ou
Snieder, Harold
Sofer, Tamar
Takeuchi, Fumihiko
Verweij, Niek
Ware, Erin B
Weiss, Stefan
Yanek, Lisa R
Amin, Najaf
Arking, Dan E
Arnett, Donna K
Bergmann, Sven
Boerwinkle, Eric
Brody, Jennifer A
Broeckel, Ulrich
Brumat, Marco
Burke, Gregory
Cabrera, Claudia P
Canouil, Mickael
Chee, Miao Li
Chen, Yii-Der Ida
Cocca, Massimiliano
Connell, John
de Silva, H Janaka
de Vries, Paul S
Eiriksdottir, Gudny
Faul, Jessica D
Fisher, Virginia
Forrester, Terrence
Fox, Ervin F
Friedlander, Yechiel
Gao, He
Gigante, Bruna
Giulianini, Franco
Gu, Chi Charles
Gu, Dongfeng
Harris, Tamara B
He, Jiang
Heikkinen, Sami
Heng, Chew-Kiat
Hunt, Steven
Ikram, M Arfan
Irvin, Marguerite R
Kahonen, Mika
Kavousi, Maryam
Khor, Chiea Chuen
Kilpelainen, Tuomas O
Koh, Woon-Puay
Komulainen, Pirjo
Kraja, Aldi T
Krieger, JE
Langefeld, Carl D
Li, Yize
Liang, Jingjing
Liewald, David CM
Liu, Ching-Ti
Liu, Jianjun
Lohman, Kurt K
Magi, Reedik
McKenzie, Colin A
Meitinger, Thomas
Metspalu, Andres
Milaneschi, Yuri
Milani, Lili
Mook-Kanamori, Dennis O
Nalls, Mike A
Nelson, Christopher P
Norris, Jill M
O'Connell, Jeff
Ogunniyi, Adesola
Padmanabhan, Sandosh
Palmer, Nicholette D
Pedersen, Nancy L
Perls, Thomas
Peters, Annette
Petersmann, Astrid
Peyser, Patricia A
Polasek, Ozren
Porteous, David J
Raffel, Leslie J
Rice, Treva K
Rotter, Jerome I
Rudan, Igor
Rueda-Ochoa, Oscar-Leonel
Sabanayagam, Charumathi
Salako, Babatunde L
Schreiner, Pamela J
Shikany, James M
Sidney, Stephen S
Sims, Mario
Sitlani, Colleen M
Smith, Jennifer A
Starr, John M
Strauch, Konstantin
Swertz, Morris A
Teumer, Alexander
Tham, Yih Chung
Uitterlinden, Andre G
Vaidya, Dhananjay
van der Ende, M Yldau
Waldenberger, Melanie
Wang, Lihua
Wang, Ya-Xing
Wei, Wen-Bin
Weir, David R
Wen, Wanqing
Yao, Jie
Yu, Bing
Yu, Caizheng
Yuan, Jian-Min
Zhao, Wei
Zonderman, Alan B
Becker, Diane M
Bowden, Donald W
Deary, Ian J
Doerr, Marcus
Esko, Tonu
Freedman, Barry I
Froguel, Philippe
Gasparini, Paolo
Gieger, Christian
Jonas, Jost Bruno
Kammerer, Candace M
Kato, Norihiro
Lakka, Timo A
Leander, Karin
Lehtimaki, Terho
Magnusson, Patrik KE
Marques-Vidal, Pedro
Penninx, Brenda WJH
Samani, Nilesh J
van der Harst, Pim
Wagenknecht, Lynne E
Wu, Tangchun
Zheng, Wei
Zhu, Xiaofeng
Bouchard, Claude
Cooper, Richard S
Correa, Adolfo
Evans, Michele K
Gudnason, Vilmundur
Hayward, Caroline
Horta, Bernardo L
Kelly, Tanika N
Kritchevsky, Stephen B
Levy, Daniel
Palmas, Walter R
Pereira, AC
Province, Michael M
Psaty, Bruce M
Ridker, Paul M
Rotimi, Charles N
Tai, E Shyong
van Dam, Rob M
van Duijn, Cornelia M
Wong, Tien Yin
Rice, Kenneth
Gauderman, W James
Morrison, Alanna C
North, Kari E
Kardia, Sharon LR
Caulfield, Mark J
Elliott, Paul
Munroe, Patricia B
Franks, Paul W
Rao, Dabeeru C
Fornage, Myriam
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Neurosciences
Psychiatry
Neurosciences & Neurology
CORONARY-HEART-DISEASE
SOCIOECONOMIC-STATUS
RISK-FACTORS
CARDIOVASCULAR-DISEASE
ESSENTIAL-HYPERTENSION
C825T POLYMORPHISM
SOCIAL-CLASS
ASSOCIATION
EXPRESSION
VARIANTS
Issue Date: 5-May-2020
Publisher: NATURE PUBLISHING GROUP
Citation: de las Fuentes, Lisa, Sung, Yun Ju, Noordam, Raymond, Winkler, Thomas, Feitosa, Mary F, Schwander, Karen, Bentley, Amy R, Brown, Michael R, Guo, Xiuqing, Manning, Alisa, Chasman, Daniel I, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Campbell, Archie, Cheng, Ching-Yu, Dorajoo, Rajkumar, Hartwig, Fernando P, Horimoto, ARVR, Li, Changwei, Li-Gao, Ruifang, Liu, Yongmei, Marten, Jonathan, Musani, Solomon K, Ntalla, Ioanna, Rankinen, Tuomo, Richard, Melissa, Sim, Xueling, Smith, Albert V, Tajuddin, Salman M, Tayo, Bamidele O, Vojinovic, Dina, Warren, Helen R, Xuan, Deng, Alver, Maris, Boissel, Mathilde, Chai, Jin-Fang, Chen, Xu, Christensen, Kaare, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Girotto, Giorgia, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Kuehnel, Brigitte, Laguzzi, Federica, Li, Xiaoyin, Lyytikainen, Leo-Pekka, Nolte, Ilja M, Poveda, Alaitz, Rauramaa, Rainer, Riaz, Muhammad, Rueedi, Rico, Shu, Xiao-ou, Snieder, Harold, Sofer, Tamar, Takeuchi, Fumihiko, Verweij, Niek, Ware, Erin B, Weiss, Stefan, Yanek, Lisa R, Amin, Najaf, Arking, Dan E, Arnett, Donna K, Bergmann, Sven, Boerwinkle, Eric, Brody, Jennifer A, Broeckel, Ulrich, Brumat, Marco, Burke, Gregory, Cabrera, Claudia P, Canouil, Mickael, Chee, Miao Li, Chen, Yii-Der Ida, Cocca, Massimiliano, Connell, John, de Silva, H Janaka, de Vries, Paul S, Eiriksdottir, Gudny, Faul, Jessica D, Fisher, Virginia, Forrester, Terrence, Fox, Ervin F, Friedlander, Yechiel, Gao, He, Gigante, Bruna, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B, He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven, Ikram, M Arfan, Irvin, Marguerite R, Kahonen, Mika, Kavousi, Maryam, Khor, Chiea Chuen, Kilpelainen, Tuomas O, Koh, Woon-Puay, Komulainen, Pirjo, Kraja, Aldi T, Krieger, JE, Langefeld, Carl D, Li, Yize, Liang, Jingjing, Liewald, David CM, Liu, Ching-Ti, Liu, Jianjun, Lohman, Kurt K, Magi, Reedik, McKenzie, Colin A, Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Milani, Lili, Mook-Kanamori, Dennis O, Nalls, Mike A, Nelson, Christopher P, Norris, Jill M, O'Connell, Jeff, Ogunniyi, Adesola, Padmanabhan, Sandosh, Palmer, Nicholette D, Pedersen, Nancy L, Perls, Thomas, Peters, Annette, Petersmann, Astrid, Peyser, Patricia A, Polasek, Ozren, Porteous, David J, Raffel, Leslie J, Rice, Treva K, Rotter, Jerome I, Rudan, Igor, Rueda-Ochoa, Oscar-Leonel, Sabanayagam, Charumathi, Salako, Babatunde L, Schreiner, Pamela J, Shikany, James M, Sidney, Stephen S, Sims, Mario, Sitlani, Colleen M, Smith, Jennifer A, Starr, John M, Strauch, Konstantin, Swertz, Morris A, Teumer, Alexander, Tham, Yih Chung, Uitterlinden, Andre G, Vaidya, Dhananjay, van der Ende, M Yldau, Waldenberger, Melanie, Wang, Lihua, Wang, Ya-Xing, Wei, Wen-Bin, Weir, David R, Wen, Wanqing, Yao, Jie, Yu, Bing, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B, Becker, Diane M, Bowden, Donald W, Deary, Ian J, Doerr, Marcus, Esko, Tonu, Freedman, Barry I, Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Jonas, Jost Bruno, Kammerer, Candace M, Kato, Norihiro, Lakka, Timo A, Leander, Karin, Lehtimaki, Terho, Magnusson, Patrik KE, Marques-Vidal, Pedro, Penninx, Brenda WJH, Samani, Nilesh J, van der Harst, Pim, Wagenknecht, Lynne E, Wu, Tangchun, Zheng, Wei, Zhu, Xiaofeng, Bouchard, Claude, Cooper, Richard S, Correa, Adolfo, Evans, Michele K, Gudnason, Vilmundur, Hayward, Caroline, Horta, Bernardo L, Kelly, Tanika N, Kritchevsky, Stephen B, Levy, Daniel, Palmas, Walter R, Pereira, AC, Province, Michael M, Psaty, Bruce M, Ridker, Paul M, Rotimi, Charles N, Tai, E Shyong, van Dam, Rob M, van Duijn, Cornelia M, Wong, Tien Yin, Rice, Kenneth, Gauderman, W James, Morrison, Alanna C, North, Kari E, Kardia, Sharon LR, Caulfield, Mark J, Elliott, Paul, Munroe, Patricia B, Franks, Paul W, Rao, Dabeeru C, Fornage, Myriam (2020-05-05). Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci. MOLECULAR PSYCHIATRY 26 (6). ScholarBank@NUS Repository. https://doi.org/10.1038/s41380-020-0719-3
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.
Source Title: MOLECULAR PSYCHIATRY
URI: https://scholarbank.nus.edu.sg/handle/10635/206003
ISSN: 13594184
14765578
DOI: 10.1038/s41380-020-0719-3
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