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

de Las Fuentes, L.; Sung, Y.J.; Noordam, R.; Winkler, T.; Feitosa, M.F.; Schwander, K.; Bentley, A.R.; Brown, M.R.; Guo, X.; Manning, A.; Chasman, D.I.; Aschard, H.; Bartz, T.M.; Bielak, L.F.; Campbell, A.; Cheng, C.Y.; Dorajoo, R.; Hartwig, F.P.; Horimoto, ARVR; Li, C.; Li-Gao, R.; Liu, Y.; Marten, J.; Musani, S.K.; Ntalla, I.; Rankinen, T.; Richard, M.; Sim, X.; Smith, A.V.; Tajuddin, S.M.; Tayo, B.O.; Vojinovic, D.; Warren, H.R.; Xuan, D.; Alver, M.; Boissel, M.; Chai, J.F.; Chen, X.; Christensen, K.; Divers, J.; Evangelou, E.; Gao, C.; Girotto, G.; Harris, S.E.; He, M.; Hsu, F.C.; Kühnel, B.; Laguzzi, F.; Li, X.; Lyytikäinen, L.P.; Nolte, I.M.; Poveda, A.; Rauramaa, R.; Riaz, M.; Rueedi, R.; Shu, X.O.; Snieder, H.; Sofer, T.; Takeuchi, F.; Verweij, N.; Ware, E.B.; Weiss, S.; Yanek, L.R.; Amin, N.; Arking, D.E.; Arnett, D.K.; Bergmann, S.; Boerwinkle, E.; Brody, J.A.; Broeckel, U.; Brumat, M.; Burke, G.; Cabrera, C.P.; Canouil, M.; Chee, M.L.; Chen, Y.I.; Cocca, M.; Connell, J.; de Silva, H.J.; de Vries, P.S.; Eiriksdottir, G.; Faul, J.D.; Fisher, V.; Forrester, T.; Fox, E.F.; Friedlander, Y.; Gao, H.; Gigante, B.; Giulianini, F.; Gu, C.C.; Gu, D.; Harris, T.B.; He, J.; Heikkinen, S.; Heng, C.K.; Hunt, S.; Ikram, M.A.; Irvin, M.R.; Kähönen, M.; Kavousi, M.; Khor, C.C.; Kilpeläinen, T.O.; Koh, W.P.; Komulainen, P.; Kraja, A.T.; Krieger, J.E.; Langefeld, C.D.; Li, Y.; Liang, J.; Liewald, DCM; Liu, C.T.; Liu, J.; Lohman, K.K.; Mägi, R.; McKenzie, C.A.; Meitinger, T.; Metspalu, A.; Milaneschi, Y.; Milani, L.; Mook-Kanamori, D.O.; Nalls, M.A.; Nelson, C.P.; Norris, J.M.; O'Connell, J.; Ogunniyi, A.; Padmanabhan, S.; Palmer, N.D.; Pedersen, N.L.; Perls, T.; Peters, A.; Petersmann, A.; Peyser, P.A.; Polasek, O.; Porteous, D.J.; Raffel, L.J.; Rice, T.K.; Rotter, J.I.; Rudan, I.; Rueda-Ochoa, O.L.; Sabanayagam, C.; Salako, B.L.; Schreiner, P.J.; Shikany, J.M.; Sidney, S.S.; Sims, M.; Sitlani, C.M.; Smith, J.A.; Starr, J.M.; Strauch, K.; Swertz, M.A.; Teumer, A.; Tham, Y.C.; Uitterlinden, A.G.; Vaidya, D.; van der Ende, M.Y.; Waldenberger, M.; Wang, L.; Wang, Y.X.; Wei, W.B.; Weir, D.R.; Wen, W.; Yao, J.; Yu, B.; Yu, C.; Yuan, J.M.; Zhao, W.; Zonderman, A.B.; Becker, D.M.; Bowden, D.W.; Deary, I.J.; Dörr, M.; Esko, T.; Freedman, B.I.; Froguel, P.; Gasparini, P.; Gieger, C.; Jonas, J.B.; Kammerer, C.M.; Kato, N.; Lakka, T.A.; Leander, K.; Lehtimäki, T.; Magnusson, PKE; Marques-Vidal, P.; Penninx, BWJH; Samani, N.J.; van der Harst, P.; Wagenknecht, L.E.; Wu, T.; Zheng, W.; Zhu, X.; Bouchard, C.; Cooper, R.S.; Correa, A.; Evans, M.K.; Gudnason, V.; Hayward, C.; Horta, B.L.; Kelly, T.N.; Kritchevsky, S.B.; Levy, D.; Palmas, W.R.; Pereira, A.C.; Province, M.M.; Psaty, B.M.; Ridker, P.M.; Rotimi, C.N.; Tai, E.S.; van Dam, R.M.; van Duijn, C.M.; Wong, T.Y.; Rice, K.; Gauderman, W.J.; Morrison, A.C.; North, K.E.; Kardia, SLR; Caulfield, M.J.; Elliott, P.; Munroe, P.B.; Franks, P.W.; Rao, D.C.; Fornage, M.

doi:10.1038/s41380-020-0719-3

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

Details

Download: 32372009_BIB_7C997FACA438.pdf (933.85 [Ko])
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Version: Author's accepted manuscript
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Serval ID

serval:BIB_7C997FACA438

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

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

Journal

Molecular psychiatry

Author(s)

de Las Fuentes L., Sung Y.J., Noordam R., Winkler T., Feitosa M.F., Schwander K., Bentley A.R., Brown M.R., Guo X., Manning A., Chasman D.I., Aschard H., Bartz T.M., Bielak L.F., Campbell A., Cheng C.Y., Dorajoo R., Hartwig F.P., Horimoto ARVR, Li C., Li-Gao R., Liu Y., Marten J., Musani S.K., Ntalla I., Rankinen T., Richard M., Sim X., Smith A.V., Tajuddin S.M., Tayo B.O., Vojinovic D., Warren H.R., Xuan D., Alver M., Boissel M., Chai J.F., Chen X., Christensen K., Divers J., Evangelou E., Gao C., Girotto G., Harris S.E., He M., Hsu F.C., Kühnel B., Laguzzi F., Li X., Lyytikäinen L.P., Nolte I.M., Poveda A., Rauramaa R., Riaz M., Rueedi R., Shu X.O., Snieder H., Sofer T., Takeuchi F., Verweij N., Ware E.B., Weiss S., Yanek L.R., Amin N., Arking D.E., Arnett D.K., Bergmann S., Boerwinkle E., Brody J.A., Broeckel U., Brumat M., Burke G., Cabrera C.P., Canouil M., Chee M.L., Chen Y.I., Cocca M., Connell J., de Silva H.J., de Vries P.S., Eiriksdottir G., Faul J.D., Fisher V., Forrester T., Fox E.F., Friedlander Y., Gao H., Gigante B., Giulianini F., Gu C.C., Gu D., Harris T.B., He J., Heikkinen S., Heng C.K., Hunt S., Ikram M.A., Irvin M.R., Kähönen M., Kavousi M., Khor C.C., Kilpeläinen T.O., Koh W.P., Komulainen P., Kraja A.T., Krieger J.E., Langefeld C.D., Li Y., Liang J., Liewald DCM, Liu C.T., Liu J., Lohman K.K., Mägi R., McKenzie C.A., Meitinger T., Metspalu A., Milaneschi Y., Milani L., Mook-Kanamori D.O., Nalls M.A., Nelson C.P., Norris J.M., O'Connell J., Ogunniyi A., Padmanabhan S., Palmer N.D., Pedersen N.L., Perls T., Peters A., Petersmann A., Peyser P.A., Polasek O., Porteous D.J., Raffel L.J., Rice T.K., Rotter J.I., Rudan I., Rueda-Ochoa O.L., Sabanayagam C., Salako B.L., Schreiner P.J., Shikany J.M., Sidney S.S., Sims M., Sitlani C.M., Smith J.A., Starr J.M., Strauch K., Swertz M.A., Teumer A., Tham Y.C., Uitterlinden A.G., Vaidya D., van der Ende M.Y., Waldenberger M., Wang L., Wang Y.X., Wei W.B., Weir D.R., Wen W., Yao J., Yu B., Yu C., Yuan J.M., Zhao W., Zonderman A.B., Becker D.M., Bowden D.W., Deary I.J., Dörr M., Esko T., Freedman B.I., Froguel P., Gasparini P., Gieger C., Jonas J.B., Kammerer C.M., Kato N., Lakka T.A., Leander K., Lehtimäki T., Magnusson PKE, Marques-Vidal P., Penninx BWJH, Samani N.J., van der Harst P., Wagenknecht L.E., Wu T., Zheng W., Zhu X., Bouchard C., Cooper R.S., Correa A., Evans M.K., Gudnason V., Hayward C., Horta B.L., Kelly T.N., Kritchevsky S.B., Levy D., Palmas W.R., Pereira A.C., Province M.M., Psaty B.M., Ridker P.M., Rotimi C.N., Tai E.S., van Dam R.M., van Duijn C.M., Wong T.Y., Rice K., Gauderman W.J., Morrison A.C., North K.E., Kardia SLR, Caulfield M.J., Elliott P., Munroe P.B., Franks P.W., Rao D.C., Fornage M.

Working group(s)

Lifelines Cohort Study

ISSN

1476-5578 (Electronic)

ISSN-L

1359-4184

Publication state

Published

Issued date

06/2021

Peer-reviewed

Oui

Volume

Number

Pages

2111-2125

Language

english

Notes

Publication types: Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish

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 <sup>-8</sup> ). 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.

Keywords

Blood Pressure/genetics, Epistasis, Genetic, Genetic Loci, Genome-Wide Association Study, Humans, Hypertension/genetics, Polymorphism, Single Nucleotide

URN

urn:nbn:ch:serval-BIB_7C997FACA4387

OAI-PMH

oai:serval.unil.ch:BIB_7C997FACA438

DOI

10.1038/s41380-020-0719-3

Pubmed

32372009

Web of science

000530592500002

Create date

16/06/2020 15:39