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


Serval ID
Article: article from journal or magazin.
Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci.
Molecular psychiatry
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
1476-5578 (Electronic)
Publication state
In Press
Publication types: Journal Article
Publication Status: aheadofprint
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.
Web of science
Create date
16/06/2020 14:39
Last modification date
31/07/2020 5:21
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