Skip to main content

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

Publication ,  Journal Article
de Las Fuentes, L; Sung, YJ; Noordam, R; Winkler, T; Feitosa, MF; Schwander, K; Bentley, AR; Brown, MR; Guo, X; Manning, A; Chasman, DI; Li, C ...
Published in: Mol Psychiatry
June 2021

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Mol Psychiatry

DOI

EISSN

1476-5578

Publication Date

June 2021

Volume

26

Issue

6

Start / End Page

2111 / 2125

Location

England

Related Subject Headings

  • Psychiatry
  • Polymorphism, Single Nucleotide
  • Hypertension
  • Humans
  • Genome-Wide Association Study
  • Genetic Loci
  • Epistasis, Genetic
  • Blood Pressure
  • 5203 Clinical and health psychology
  • 5202 Biological psychology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
de Las Fuentes, L., Sung, Y. J., Noordam, R., Winkler, T., Feitosa, M. F., Schwander, K., … Fornage, M. (2021). Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci. Mol Psychiatry, 26(6), 2111–2125. https://doi.org/10.1038/s41380-020-0719-3
Las Fuentes, Lisa de, Yun Ju Sung, Raymond Noordam, Thomas Winkler, Mary F. Feitosa, Karen Schwander, Amy R. Bentley, et al. “Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci.Mol Psychiatry 26, no. 6 (June 2021): 2111–25. https://doi.org/10.1038/s41380-020-0719-3.
de Las Fuentes L, Sung YJ, Noordam R, Winkler T, Feitosa MF, Schwander K, et al. Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci. Mol Psychiatry. 2021 Jun;26(6):2111–25.
de Las Fuentes, Lisa, et al. “Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci.Mol Psychiatry, vol. 26, no. 6, June 2021, pp. 2111–25. Pubmed, doi:10.1038/s41380-020-0719-3.
de Las Fuentes L, Sung YJ, 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, Kühnel 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 ML, Chen Y-DI, Cocca M, Connell J, de Silva HJ, de Vries PS, Eiriksdottir G, Faul JD, Fisher V, Forrester T, Fox EF, Friedlander Y, Gao H, Gigante B, Giulianini F, Gu CC, Gu D, Harris TB, He J, Heikkinen S, Heng C-K, Hunt S, Ikram MA, Irvin MR, Kähönen M, Kavousi M, Khor CC, 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 YC, Uitterlinden AG, Vaidya D, van der Ende MY, Waldenberger M, Wang L, Wang Y-X, Wei W-B, 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 JB, Kammerer CM, Kato N, Lakka TA, Leander K, Lehtimäki T, Lifelines Cohort Study, 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 ES, van Dam RM, van Duijn CM, Wong TY, Rice K, Gauderman WJ, Morrison AC, North KE, Kardia SLR, Caulfield MJ, Elliott P, Munroe PB, Franks PW, Rao DC, Fornage M. Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci. Mol Psychiatry. 2021 Jun;26(6):2111–2125.

Published In

Mol Psychiatry

DOI

EISSN

1476-5578

Publication Date

June 2021

Volume

26

Issue

6

Start / End Page

2111 / 2125

Location

England

Related Subject Headings

  • Psychiatry
  • Polymorphism, Single Nucleotide
  • Hypertension
  • Humans
  • Genome-Wide Association Study
  • Genetic Loci
  • Epistasis, Genetic
  • Blood Pressure
  • 5203 Clinical and health psychology
  • 5202 Biological psychology