Gene-Age Interactions in Blood Pressure Regulation: A Large-Scale Investigation with the CHARGE, Global BPgen, and ICBP Consortia.

Simino, J.; Shi, G.; Bis, J.C.; Chasman, D.I.; Ehret, G.B.; Gu, X.; Guo, X.; Hwang, S.J.; Sijbrands, E.; Smith, A.V.; Verwoert, G.C.; Bragg-Gresham, J.L.; Cadby, G.; Chen, P.; Cheng, C.Y.; Corre, T.; de Boer, R.A.; Goel, A.; Johnson, T.; Khor, C.C.; Lluís-Ganella, C.; Lluís-Ganella, C.; Luan, J.; Lyytikäinen, L.P.; Nolte, I.M.; Sim, X.; Sõber, S.; van der Most, P.J.; Verweij, N.; Zhao, J.H.; Amin, N.; Boerwinkle, E.; Bouchard, C.; Dehghan, A.; Eiriksdottir, G.; Elosua, R.; Franco, O.H.; Gieger, C.; Harris, T.B.; Hercberg, S.; Hofman, A.; James, A.L.; Johnson, A.D.; Kähönen, M.; Khaw, K.T.; Kutalik, Z.; Larson, M.G.; Launer, L.J.; Li, G.; Liu, J.; Liu, K.; Morrison, A.C.; Navis, G.; Ong, R.T.; Papanicolau, G.J.; Penninx, B.W.; Psaty, B.M.; Raffel, L.J.; Raitakari, O.T.; Rice, K.; Rivadeneira, F.; Rose, L.M.; Sanna, S.; Scott, R.A.; Siscovick, D.S.; Stolk, R.P.; Uitterlinden, A.G.; Vaidya, D.; van der Klauw, M.M.; Vasan, R.S.; Vithana, E.N.; Völker, U.; Völzke, H.; Watkins, H.; Young, T.L.; Aung, T.; Bochud, M.; Farrall, M.; Hartman, C.A.; Laan, M.; Lakatta, E.G.; Lehtimäki, T.; Loos, R.J.; Lucas, G.; Meneton, P.; Palmer, L.J.; Rettig, R.; Snieder, H.; Tai, E.S.; Teo, Y.Y.; van der Harst, P.; Wareham, N.J.; Wijmenga, C.; Wong, T.Y.; Fornage, M.; Gudnason, V.; Levy, D.; Palmas, W.; Ridker, P.M.; Rotter, J.I.; van Duijn, C.M.; Witteman, J.C.; Chakravarti, A.; Rao, D.C.

doi:10.1016/j.ajhg.2014.05.010

Gene-Age Interactions in Blood Pressure Regulation: A Large-Scale Investigation with the CHARGE, Global BPgen, and ICBP Consortia.

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Serval ID

serval:BIB_86236798F95A

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

Gene-Age Interactions in Blood Pressure Regulation: A Large-Scale Investigation with the CHARGE, Global BPgen, and ICBP Consortia.

Journal

American Journal of Human Genetics

Author(s)

Simino J., Shi G., Bis J.C., Chasman D.I., Ehret G.B., Gu X., Guo X., Hwang S.J., Sijbrands E., Smith A.V., Verwoert G.C., Bragg-Gresham J.L., Cadby G., Chen P., Cheng C.Y., Corre T., de Boer R.A., Goel A., Johnson T., Khor C.C., Lluís-Ganella C., Lluís-Ganella C., Luan J., Lyytikäinen L.P., Nolte I.M., Sim X., Sõber S., van der Most P.J., Verweij N., Zhao J.H., Amin N., Boerwinkle E., Bouchard C., Dehghan A., Eiriksdottir G., Elosua R., Franco O.H., Gieger C., Harris T.B., Hercberg S., Hofman A., James A.L., Johnson A.D., Kähönen M., Khaw K.T., Kutalik Z., Larson M.G., Launer L.J., Li G., Liu J., Liu K., Morrison A.C., Navis G., Ong R.T., Papanicolau G.J., Penninx B.W., Psaty B.M., Raffel L.J., Raitakari O.T., Rice K., Rivadeneira F., Rose L.M., Sanna S., Scott R.A., Siscovick D.S., Stolk R.P., Uitterlinden A.G., Vaidya D., van der Klauw M.M., Vasan R.S., Vithana E.N., Völker U., Völzke H., Watkins H., Young T.L., Aung T., Bochud M., Farrall M., Hartman C.A., Laan M., Lakatta E.G., Lehtimäki T., Loos R.J., Lucas G., Meneton P., Palmer L.J., Rettig R., Snieder H., Tai E.S., Teo Y.Y., van der Harst P., Wareham N.J., Wijmenga C., Wong T.Y., Fornage M., Gudnason V., Levy D., Palmas W., Ridker P.M., Rotter J.I., van Duijn C.M., Witteman J.C., Chakravarti A., Rao D.C.

Working group(s)

LifeLines Cohort Study

Contributor(s)

Alizadeh BZ., de Boer RA. , Boezen HM., Bruinenberg M., Franke L., van der Harst P., Hillege HL., van der Klauw MM. , Navis G., Ormel J., Postma DS., Rosmalen JG., Slaets JP., Snieder H., Stolk RP., Wolffenbuttel BH., Wijmenga C.

ISSN

1537-6605 (Electronic)

ISSN-L

0002-9297

Publication state

Published

Issued date

2014

Peer-reviewed

Oui

Volume

Number

Pages

24-38

Language

english

Notes

Publication types: Journal Article Publication Status: ppublish PDF : Article

Abstract

Although age-dependent effects on blood pressure (BP) have been reported, they have not been systematically investigated in large-scale genome-wide association studies (GWASs). We leveraged the infrastructure of three well-established consortia (CHARGE, GBPgen, and ICBP) and a nonstandard approach (age stratification and metaregression) to conduct a genome-wide search of common variants with age-dependent effects on systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse (PP) pressure. In a two-staged design using 99,241 individuals of European ancestry, we identified 20 genome-wide significant (p ≤ 5 × 10(-8)) loci by using joint tests of the SNP main effect and SNP-age interaction. Nine of the significant loci demonstrated nominal evidence of age-dependent effects on BP by tests of the interactions alone. Index SNPs in the EHBP1L1 (DBP and MAP), CASZ1 (SBP and MAP), and GOSR2 (PP) loci exhibited the largest age interactions, with opposite directions of effect in the young versus the old. The changes in the genetic effects over time were small but nonnegligible (up to 1.58 mm Hg over 60 years). The EHBP1L1 locus was discovered through gene-age interactions only in whites but had DBP main effects replicated (p = 8.3 × 10(-4)) in 8,682 Asians from Singapore, indicating potential interethnic heterogeneity. A secondary analysis revealed 22 loci with evidence of age-specific effects (e.g., only in 20 to 29-year-olds). Age can be used to select samples with larger genetic effect sizes and more homogenous phenotypes, which may increase statistical power. Age-dependent effects identified through novel statistical approaches can provide insight into the biology and temporal regulation underlying BP associations.

OAI-PMH

oai:serval.unil.ch:BIB_86236798F95A

DOI

10.1016/j.ajhg.2014.05.010

Pubmed

24954895

Web of science

000338904100002

Open Access

Yes

Create date

08/08/2014 18:58