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

TitleGene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci.
Publication TypeJournal Article
Year of Publication2020
AuthorsFuentes, 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, 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, MLi, Chen, Y-DIda, 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, M Ikram, A, 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, E Tai, S, 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 AuthorsLifeLines Cohort Study
JournalMol Psychiatry
Date Published2020 May 05
ISSN1476-5578
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 

DOI10.1038/s41380-020-0719-3
Alternate JournalMol Psychiatry
PubMed ID32372009
PubMed Central IDPMC7641978
Grant ListR01 HD042157 / HD / NICHD NIH HHS / United States
R01 DK101855 / DK / NIDDK NIH HHS / United States
U01 HL072518 / HL / NHLBI NIH HHS / United States
RC2 MH089951 / MH / NIMH NIH HHS / United States
MC_UU_00007/10 / MRC_ / Medical Research Council / United Kingdom
U10 HL054472 / HL / NHLBI NIH HHS / United States
RC4 AG039029 / AG / NIA NIH HHS / United States
R01 HL071025 / HL / NHLBI NIH HHS / United States
U01 HL054471 / HL / NHLBI NIH HHS / United States
R01 HL103612 / HL / NHLBI NIH HHS / United States
HHSN268201300005C / HL / NHLBI NIH HHS / United States
U10 HL054497 / HL / NHLBI NIH HHS / United States
R01 HL053353 / HL / NHLBI NIH HHS / United States
R01 DK085175 / DK / NIDDK NIH HHS / United States
Z01 AG000513 / ImNIH / Intramural NIH HHS / United States
R01 HG003054 / HG / NHGRI NIH HHS / United States
N01AG12100 / AG / NIA NIH HHS / United States
N1AG62101A / AG / NIA NIH HHS / United States
R01 MH081802 / MH / NIMH NIH HHS / United States
N01HC95160 / HL / NHLBI NIH HHS / United States
U01 HG004446 / HG / NHGRI NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
R01 HL087698 / HL / NHLBI NIH HHS / United States
R01 HL071917 / HL / NHLBI NIH HHS / United States
R03 AG046389 / AG / NIA NIH HHS / United States
NNF17OC0026848 / / Novo Nordisk Fonden (Novo Nordisk Foundation) /
U10 HL054509 / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
U01 AG009740 / AG / NIA NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
RC2 MH089995 / MH / NIMH NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
Z01 HG200362 / ImNIH / Intramural NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
R01 HL087660 / HL / NHLBI NIH HHS / United States
R01 HL085251 / HL / NHLBI NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
R01 HL074166 / HL / NHLBI NIH HHS / United States
N01HC65236 / HL / NHLBI NIH HHS / United States
R37 HL045508 / HL / NHLBI NIH HHS / United States
R01 CA144034 / CA / NCI NIH HHS / United States
ZIA EY000401 / ImNIH / Intramural NIH HHS / United States
HHSN268201300048C / HL / NHLBI NIH HHS / United States
N01HC65235 / HL / NHLBI NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
K25 HL121091 / HL / NHLBI NIH HHS / United States
UM1 CA173640 / CA / NCI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
U01 HG004424 / HG / NHGRI NIH HHS / United States
R01 DK075787 / DK / NIDDK NIH HHS / United States
N01HC95164 / HL / NHLBI NIH HHS / United States
K23 HL105897 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
MR/L01341X/1 / MRC_ / Medical Research Council / United Kingdom
MR/K026992/1 / MRC_ / Medical Research Council / United Kingdom
N02HL64278 / HL / NHLBI NIH HHS / United States
R01 DK075681 / DK / NIDDK NIH HHS / United States
R01 HL060944 / HL / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
N01HC65234 / HL / NHLBI NIH HHS / United States
N01HC95162 / HL / NHLBI NIH HHS / United States
U01 HL054464 / HL / NHLBI NIH HHS / United States
R01 HL119443 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
N01HC95168 / HL / NHLBI NIH HHS / United States
R01 HL118305 / HL / NHLBI NIH HHS / United States
R01 AG032098 / AG / NIA NIH HHS / United States
U01 DK066134 / DK / NIDDK NIH HHS / United States
R01 HL067348 / HL / NHLBI NIH HHS / United States
U10 HL054457 / HL / NHLBI NIH HHS / United States
U01 HG004729 / HG / NHGRI NIH HHS / United States
U01 CA182876 / CA / NCI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
N01HC65233 / HL / NHLBI NIH HHS / United States
N01HC65237 / HL / NHLBI NIH HHS / United States
R01 HL061019 / HL / NHLBI NIH HHS / United States
N01HC95165 / HL / NHLBI NIH HHS / United States
N01HC95159 / HL / NHLBI NIH HHS / United States
M01 RR000052 / RR / NCRR NIH HHS / United States
RC1 HL099747 / HL / NHLBI NIH HHS / United States
N1AG62103A / AG / NIA NIH HHS / United States
R01 LM010098 / LM / NLM NIH HHS / United States
N01HC95161 / HL / NHLBI NIH HHS / United States
UL1 TR001420 / TR / NCATS NIH HHS / United States
R01HL118305 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) /
HHSN268201300050C / HL / NHLBI NIH HHS / United States
N01HC65226 / HL / NHLBI NIH HHS / United States
UM1 CA182913 / CA / NCI NIH HHS / United States
M01 RR007122 / RR / NCRR NIH HHS / United States
U01 AG052409 / AG / NIA NIH HHS / United States
R01 CA047988 / CA / NCI NIH HHS / United States
M01 RR010284 / RR / NCRR NIH HHS / United States
R01 HL087263 / HL / NHLBI NIH HHS / United States
MR/R023484/1 / MRC_ / Medical Research Council / United Kingdom
R01 HL080467 / HL / NHLBI NIH HHS / United States
N01HC85082 / HL / NHLBI NIH HHS / United States
U01 HL072507 / HL / NHLBI NIH HHS / United States
R01 DK071891 / DK / NIDDK NIH HHS / United States
R01 DK089256 / DK / NIDDK NIH HHS / United States
N01HC95167 / HL / NHLBI NIH HHS / United States
R01 HL086718 / HL / NHLBI NIH HHS / United States
U01 AG023746 / AG / NIA NIH HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
R01 HL060919 / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
U01 HL054481 / HL / NHLBI NIH HHS / United States
HHSN268201300046C / HL / NHLBI NIH HHS / United States
S06 GM008016 / GM / NIGMS NIH HHS / United States
U10 HL054473 / HL / NHLBI NIH HHS / United States
UL1 TR000040 / TR / NCATS NIH HHS / United States
RC2 AG036495 / AG / NIA NIH HHS / United States
U10 HL054495 / HL / NHLBI NIH HHS / United States
U10 HL054496 / HL / NHLBI NIH HHS / United States
HHSN268201200054C / HL / NHLBI NIH HHS / United States
N01HC95166 / HL / NHLBI NIH HHS / United States
R01 HL117078 / HL / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
R01 HL092165 / HL / NHLBI NIH HHS / United States
R01 HL090682 / HL / NHLBI NIH HHS / United States
UM1 CA182910 / CA / NCI NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States
R01 NS062059 / NS / NINDS NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
HHSN271201200022C / DA / NIDA NIH HHS / United States
MR/S019669/1 / MRC_ / Medical Research Council / United Kingdom
R01 HL055673 / HL / NHLBI NIH HHS / United States
R01 HL092301 / HL / NHLBI NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
UM1 CA182876 / CA / NCI NIH HHS / United States
R01 HL045670 / HL / NHLBI NIH HHS / United States