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.
| Original language | English |
|---|---|
| Pages (from-to) | 2111-2125 |
| Number of pages | 15 |
| Journal | Molecular Psychiatry |
| Volume | 26 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 2021 |
Cite this
- APA
- Author
- BIBTEX
- Harvard
- Standard
- RIS
- Vancouver
}
Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci. / de las Fuentes, Lisa; Sung, Yun Ju; Noordam, Raymond et al.
In: Molecular Psychiatry, Vol. 26, No. 6, 06.2021, p. 2111-2125.Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci
AU - de las Fuentes, Lisa
AU - Sung, Yun Ju
AU - Noordam, Raymond
AU - Winkler, Thomas
AU - Feitosa, Mary F.
AU - Schwander, Karen
AU - Bentley, Amy R.
AU - Brown, Michael R.
AU - Guo, Xiuqing
AU - Manning, Alisa
AU - Chasman, Daniel I.
AU - Aschard, Hugues
AU - Bartz, Traci M.
AU - Bielak, Lawrence F.
AU - Campbell, Archie
AU - Cheng, Ching Yu
AU - Dorajoo, Rajkumar
AU - Hartwig, Fernando P.
AU - Horimoto, A. R.V.R.
AU - Li, Changwei
AU - Li-Gao, Ruifang
AU - Liu, Yongmei
AU - Marten, Jonathan
AU - Musani, Solomon K.
AU - Ntalla, Ioanna
AU - Rankinen, Tuomo
AU - Richard, Melissa
AU - Sim, Xueling
AU - Smith, Albert V.
AU - Tajuddin, Salman M.
AU - Tayo, Bamidele O.
AU - Vojinovic, Dina
AU - Warren, Helen R.
AU - Xuan, Deng
AU - Alver, Maris
AU - Boissel, Mathilde
AU - Chai, Jin Fang
AU - Chen, Xu
AU - Christensen, Kaare
AU - Divers, Jasmin
AU - Evangelou, Evangelos
AU - Gao, Chuan
AU - Girotto, Giorgia
AU - Harris, Sarah E.
AU - He, Meian
AU - Hsu, Fang Chi
AU - Kühnel, Brigitte
AU - Laguzzi, Federica
AU - Li, Xiaoyin
AU - Lyytikäinen, Leo Pekka
AU - Nolte, Ilja M.
AU - Poveda, Alaitz
AU - Rauramaa, Rainer
AU - Riaz, Muhammad
AU - Rueedi, Rico
AU - Shu, Xiao ou
AU - Snieder, Harold
AU - Sofer, Tamar
AU - Takeuchi, Fumihiko
AU - Verweij, Niek
AU - Ware, Erin B.
AU - Weiss, Stefan
AU - Yanek, Lisa R.
AU - Amin, Najaf
AU - Arking, Dan E.
AU - Arnett, Donna K.
AU - Bergmann, Sven
AU - Boerwinkle, Eric
AU - Brody, Jennifer A.
AU - Broeckel, Ulrich
AU - Brumat, Marco
AU - Burke, Gregory
AU - Cabrera, Claudia P.
AU - Canouil, Mickaël
AU - Chee, Miao Li
AU - Chen, Yii Der Ida
AU - Cocca, Massimiliano
AU - Connell, John
AU - de Silva, H. Janaka
AU - de Vries, Paul S.
AU - Eiriksdottir, Gudny
AU - Faul, Jessica D.
AU - Fisher, Virginia
AU - Forrester, Terrence
AU - Fox, Ervin F.
AU - Friedlander, Yechiel
AU - Gao, He
AU - Gigante, Bruna
AU - Giulianini, Franco
AU - Gu, Chi Charles
AU - Gu, Dongfeng
AU - Harris, Tamara B.
AU - He, Jiang
AU - Heikkinen, Sami
AU - Heng, Chew Kiat
AU - Hunt, Steven
AU - Ikram, M. Arfan
AU - Irvin, Marguerite R.
AU - Kähönen, Mika
AU - Kavousi, Maryam
AU - Khor, Chiea Chuen
AU - Kilpeläinen, Tuomas O.
AU - Koh, Woon Puay
AU - Komulainen, Pirjo
AU - Kraja, Aldi T.
AU - Krieger, J. E.
AU - Langefeld, Carl D.
AU - Li, Yize
AU - Liang, Jingjing
AU - Liewald, David C.M.
AU - Liu, Ching Ti
AU - Liu, Jianjun
AU - Lohman, Kurt K.
AU - Mägi, Reedik
AU - McKenzie, Colin A.
AU - Meitinger, Thomas
AU - Metspalu, Andres
AU - Milaneschi, Yuri
AU - Milani, Lili
AU - Mook-Kanamori, Dennis O.
AU - Nalls, Mike A.
AU - Nelson, Christopher P.
AU - Norris, Jill M.
AU - O’Connell, Jeff
AU - Ogunniyi, Adesola
AU - Padmanabhan, Sandosh
AU - Palmer, Nicholette D.
AU - Pedersen, Nancy L.
AU - Perls, Thomas
AU - Peters, Annette
AU - Petersmann, Astrid
AU - Peyser, Patricia A.
AU - Polasek, Ozren
AU - Porteous, David J.
AU - Raffel, Leslie J.
AU - Rice, Treva K.
AU - Rotter, Jerome I.
AU - Rudan, Igor
AU - Rueda-Ochoa, Oscar Leonel
AU - Sabanayagam, Charumathi
AU - Salako, Babatunde L.
AU - Schreiner, Pamela J.
AU - Shikany, James M.
AU - Sidney, Stephen S.
AU - Sims, Mario
AU - Sitlani, Colleen M.
AU - Smith, Jennifer A.
AU - Starr, John M.
AU - Strauch, Konstantin
AU - Swertz, Morris A.
AU - Teumer, Alexander
AU - Tham, Yih Chung
AU - Uitterlinden, André G.
AU - Vaidya, Dhananjay
AU - van der Ende, M. Yldau
AU - Waldenberger, Melanie
AU - Wang, Lihua
AU - Wang, Ya Xing
AU - Wei, Wen Bin
AU - Weir, David R.
AU - Wen, Wanqing
AU - Yao, Jie
AU - Yu, Bing
AU - Yu, Caizheng
AU - Yuan, Jian Min
AU - Zhao, Wei
AU - Zonderman, Alan B.
AU - Becker, Diane M.
AU - Bowden, Donald W.
AU - Deary, Ian J.
AU - Dörr, Marcus
AU - Esko, Tõnu
AU - Freedman, Barry I.
AU - Froguel, Philippe
AU - Gasparini, Paolo
AU - Gieger, Christian
AU - Jonas, Jost Bruno
AU - Kammerer, Candace M.
AU - Kato, Norihiro
AU - Lakka, Timo A.
AU - Leander, Karin
AU - Lehtimäki, Terho
AU - Magnusson, Patrik K.E.
AU - Marques-Vidal, Pedro
AU - Penninx, Brenda W.J.H.
AU - Samani, Nilesh J.
AU - van der Harst, Pim
AU - Wagenknecht, Lynne E.
AU - Wu, Tangchun
AU - Zheng, Wei
AU - Zhu, Xiaofeng
AU - Bouchard, Claude
AU - Cooper, Richard S.
AU - Correa, Adolfo
AU - Evans, Michele K.
AU - Gudnason, Vilmundur
AU - Hayward, Caroline
AU - Horta, Bernardo L.
AU - Kelly, Tanika N.
AU - Kritchevsky, Stephen B.
AU - Levy, Daniel
AU - Palmas, Walter R.
AU - Pereira, A. C.
AU - Province, Michael M.
AU - Psaty, Bruce M.
AU - Ridker, Paul M.
AU - Rotimi, Charles N.
AU - Tai, E. Shyong
AU - van Dam, Rob M.
AU - van Duijn, Cornelia M.
AU - Wong, Tien Yin
AU - Rice, Kenneth
AU - Gauderman, W. James
AU - Morrison, Alanna C.
AU - North, Kari E.
AU - Kardia, Sharon L.R.
AU - Caulfield, Mark J.
AU - Elliott, Paul
AU - Munroe, Patricia B.
AU - Franks, Paul W.
AU - Rao, Dabeeru C.
AU - Fornage, Myriam
AU - Lifelines Cohort Study
PY - 2021/6
Y1 - 2021/6
N2 - 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.
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 × 10-8). 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.
UR - http://www.scopus.com/inward/record.url?scp=85085119426&partnerID=8YFLogxK
U2 - 10.1038/s41380-020-0719-3
DO - 10.1038/s41380-020-0719-3
M3 - Article
C2 - 32372009
AN - SCOPUS:85085119426
VL - 26
SP - 2111
EP - 2125
JO - Molecular Psychiatry
JF - Molecular Psychiatry
SN - 1359-4184
IS - 6
ER -