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Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci.
Monday,2020-08-10 17:39 America/Los_Angeles — ecterry
| Title | Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci. |
| Publication Type | Journal Article |
| Year of Publication | 2020 |
| Authors | Fuentes, Lde Las, Sung, YJu, Noordam, R, Winkler, T, Feitosa, MF, Schwander, K, Bentley, AR, Brown, MR, Guo, X, Manning, A, Chasman, DI, Aschard, H, Bartz, TM, Bielak, LF, Campbell, A, Cheng, C-Y, Dorajoo, R, Hartwig, FP, Horimoto, ARVR, Li, C, Li-Gao, R, Liu, Y, Marten, J, Musani, SK, Ntalla, I, Rankinen, T, Richard, M, Sim, X, Smith, AV, Tajuddin, SM, Tayo, BO, Vojinovic, D, Warren, HR, Xuan, D, Alver, M, Boissel, M, Chai, J-F, Chen, X, Christensen, K, Divers, J, Evangelou, E, Gao, C, Girotto, G, Harris, SE, He, M, Hsu, F-C, Kuhnel, B, Laguzzi, F, Li, X, Lyytikäinen, L-P, Nolte, IM, Poveda, A, Rauramaa, R, Riaz, M, Rueedi, R, Shu, X-O, Snieder, H, Sofer, T, Takeuchi, F, Verweij, N, Ware, EB, Weiss, S, Yanek, LR, Amin, N, Arking, DE, Arnett, DK, Bergmann, S, Boerwinkle, E, Brody, JA, Broeckel, U, Brumat, M, Burke, G, Cabrera, CP, Canouil, M, Chee, MLi, Chen, Y-DI, Cocca, M, Connell, J, H de Silva, J, de Vries, PS, Eiriksdottir, G, Faul, JD, Fisher, V, Forrester, T, Fox, EF, Friedlander, Y, Gao, H, Gigante, B, Giulianini, F, Gu, CCharles, Gu, D, Harris, TB, He, J, Heikkinen, S, Heng, C-K, Hunt, S, Ikram, AM, Irvin, MR, Kähönen, M, Kavousi, M, Khor, CChuen, Kilpeläinen, TO, Koh, W-P, Komulainen, P, Kraja, AT, Krieger, JE, Langefeld, CD, Li, Y, Liang, J, Liewald, DCM, Liu, C-T, Liu, J, Lohman, KK, Mägi, R, McKenzie, CA, Meitinger, T, Metspalu, A, Milaneschi, Y, Milani, L, Mook-Kanamori, DO, Nalls, MA, Nelson, CP, Norris, JM, O'Connell, J, Ogunniyi, A, Padmanabhan, S, Palmer, ND, Pedersen, NL, Perls, T, Peters, A, Petersmann, A, Peyser, PA, Polasek, O, Porteous, DJ, Raffel, LJ, Rice, TK, Rotter, JI, Rudan, I, Rueda-Ochoa, O-L, Sabanayagam, C, Salako, BL, Schreiner, PJ, Shikany, JM, Sidney, SS, Sims, M, Sitlani, CM, Smith, JA, Starr, JM, Strauch, K, Swertz, MA, Teumer, A, Tham, YChung, Uitterlinden, AG, Vaidya, D, M van der Ende, Y, Waldenberger, M, Wang, L, Wang, Y-X, Bin Wei, W-, Weir, DR, Wen, W, Yao, J, Yu, B, Yu, C, Yuan, J-M, Zhao, W, Zonderman, AB, Becker, DM, Bowden, DW, Deary, IJ, Dörr, M, Esko, T, Freedman, BI, Froguel, P, Gasparini, P, Gieger, C, Jonas, JBruno, Kammerer, CM, Kato, N, Lakka, TA, Leander, K, Lehtimäki, T, Magnusson, PKE, Marques-Vidal, P, Penninx, BWJH, Samani, NJ, van der Harst, P, Wagenknecht, LE, Wu, T, Zheng, W, Zhu, X, Bouchard, C, Cooper, RS, Correa, A, Evans, MK, Gudnason, V, Hayward, C, Horta, BL, Kelly, TN, Kritchevsky, SB, Levy, D, Palmas, WR, Pereira, AC, Province, MM, Psaty, BM, Ridker, PM, Rotimi, CN, Tai, SE, van Dam, RM, van Duijn, CM, Wong, TYin, Rice, K, W Gauderman, J, Morrison, AC, North, KE, Kardia, SLR, Caulfield, MJ, Elliott, P, Munroe, PB, Franks, PW, Rao, DC, Fornage, M |
| Corporate/Institutional Authors | LifeLines Cohort Study, |
| Journal | Mol Psychiatry |
| Date Published | 2020 May 05 |
| ISSN | 1476-5578 |
| Abstract | <p>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.</p> |
| DOI | 10.1038/s41380-020-0719-3 |
| Alternate Journal | Mol. Psychiatry |
| PubMed ID | 32372009 |
| Grant List | R01 DK085175 / DK / NIDDK NIH HHS / United States R01 HL120393 / HL / NHLBI NIH HHS / United States NNF17OC0026848 / / Novo Nordisk Fonden (Novo Nordisk Foundation) / U01 HL130114 / HL / NHLBI NIH HHS / United States R01 DK089256 / DK / NIDDK NIH HHS / United States R01HL118305 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) / UM1 CA182913 / CA / NCI NIH HHS / United States R01 CA047988 / CA / NCI NIH HHS / United States U01 AG052409 / AG / NIA NIH HHS / United States |
ePub date:
20/05