Effects of the coronary artery disease associated LPA and 9p21 loci on risk of aortic valve stenosis

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Effects of the coronary artery disease associated LPA and 9p21 loci on risk of aortic valve stenosis. / Trenkwalder, Teresa; Nelson, Christopher P.; Musameh, Muntaser D.; Mordi, Ify R.; Kessler, Thorsten; Pellegrini, Costanza; Debiec, Radoslaw; Rheude, Tobias; Lazovic, Viktor; Zeng, Lingyao; Martinsson, Andreas; Gustav Smith, J.; Gådin, Jesper R.; Franco-Cereceda, Anders; Eriksson, Per; Nielsen, Jonas B.; Graham, Sarah E.; Willer, Cristen J.; Hveem, Kristian; Kastrati, Adnan; Braund, Peter S.; Palmer, Colin N.A.; Aracil, Amparo; Husser, Oliver; Koenig, Wolfgang; Schunkert, Heribert; Lang, Chim C.; Hengstenberg, Christian; Samani, Nilesh J.

In: International Journal of Cardiology, Vol. 276, 02.2019, p. 212-217.

Research output: Contribution to journalArticle

Harvard

Trenkwalder, T, Nelson, CP, Musameh, MD, Mordi, IR, Kessler, T, Pellegrini, C, Debiec, R, Rheude, T, Lazovic, V, Zeng, L, Martinsson, A, Gustav Smith, J, Gådin, JR, Franco-Cereceda, A, Eriksson, P, Nielsen, JB, Graham, SE, Willer, CJ, Hveem, K, Kastrati, A, Braund, PS, Palmer, CNA, Aracil, A, Husser, O, Koenig, W, Schunkert, H, Lang, CC, Hengstenberg, C & Samani, NJ 2019, 'Effects of the coronary artery disease associated LPA and 9p21 loci on risk of aortic valve stenosis', International Journal of Cardiology, vol. 276, pp. 212-217. https://doi.org/10.1016/j.ijcard.2018.11.094

APA

Trenkwalder, T., Nelson, C. P., Musameh, M. D., Mordi, I. R., Kessler, T., Pellegrini, C., Debiec, R., Rheude, T., Lazovic, V., Zeng, L., Martinsson, A., Gustav Smith, J., Gådin, J. R., Franco-Cereceda, A., Eriksson, P., Nielsen, J. B., Graham, S. E., Willer, C. J., Hveem, K., ... Samani, N. J. (2019). Effects of the coronary artery disease associated LPA and 9p21 loci on risk of aortic valve stenosis. International Journal of Cardiology, 276, 212-217. https://doi.org/10.1016/j.ijcard.2018.11.094

CBE

Trenkwalder T, Nelson CP, Musameh MD, Mordi IR, Kessler T, Pellegrini C, Debiec R, Rheude T, Lazovic V, Zeng L, Martinsson A, Gustav Smith J, Gådin JR, Franco-Cereceda A, Eriksson P, Nielsen JB, Graham SE, Willer CJ, Hveem K, Kastrati A, Braund PS, Palmer CNA, Aracil A, Husser O, Koenig W, Schunkert H, Lang CC, Hengstenberg C, Samani NJ. 2019. Effects of the coronary artery disease associated LPA and 9p21 loci on risk of aortic valve stenosis. International Journal of Cardiology. 276:212-217. https://doi.org/10.1016/j.ijcard.2018.11.094

MLA

Vancouver

Author

Trenkwalder, Teresa ; Nelson, Christopher P. ; Musameh, Muntaser D. ; Mordi, Ify R. ; Kessler, Thorsten ; Pellegrini, Costanza ; Debiec, Radoslaw ; Rheude, Tobias ; Lazovic, Viktor ; Zeng, Lingyao ; Martinsson, Andreas ; Gustav Smith, J. ; Gådin, Jesper R. ; Franco-Cereceda, Anders ; Eriksson, Per ; Nielsen, Jonas B. ; Graham, Sarah E. ; Willer, Cristen J. ; Hveem, Kristian ; Kastrati, Adnan ; Braund, Peter S. ; Palmer, Colin N.A. ; Aracil, Amparo ; Husser, Oliver ; Koenig, Wolfgang ; Schunkert, Heribert ; Lang, Chim C. ; Hengstenberg, Christian ; Samani, Nilesh J. / Effects of the coronary artery disease associated LPA and 9p21 loci on risk of aortic valve stenosis. In: International Journal of Cardiology. 2019 ; Vol. 276. pp. 212-217.

RIS

TY - JOUR

T1 - Effects of the coronary artery disease associated LPA and 9p21 loci on risk of aortic valve stenosis

AU - Trenkwalder, Teresa

AU - Nelson, Christopher P.

AU - Musameh, Muntaser D.

AU - Mordi, Ify R.

AU - Kessler, Thorsten

AU - Pellegrini, Costanza

AU - Debiec, Radoslaw

AU - Rheude, Tobias

AU - Lazovic, Viktor

AU - Zeng, Lingyao

AU - Martinsson, Andreas

AU - Gustav Smith, J.

AU - Gådin, Jesper R.

AU - Franco-Cereceda, Anders

AU - Eriksson, Per

AU - Nielsen, Jonas B.

AU - Graham, Sarah E.

AU - Willer, Cristen J.

AU - Hveem, Kristian

AU - Kastrati, Adnan

AU - Braund, Peter S.

AU - Palmer, Colin N.A.

AU - Aracil, Amparo

AU - Husser, Oliver

AU - Koenig, Wolfgang

AU - Schunkert, Heribert

AU - Lang, Chim C.

AU - Hengstenberg, Christian

AU - Samani, Nilesh J.

PY - 2019/2

Y1 - 2019/2

N2 - Background: Aortic valve stenosis (AVS) and coronary artery disease (CAD) have a significant genetic contribution and commonly co-exist. To compare and contrast genetic determinants of the two diseases, we investigated associations of the LPA and 9p21 loci, i.e. the two strongest CAD risk loci, with risk of AVS. Methods: We genotyped the CAD-associated variants at the LPA (rs10455872) and 9p21 loci (rs1333049) in the GeneCAST (Genetics of Calcific Aortic STenosis) Consortium and conducted a meta-analysis for their association with AVS. Cases and controls were stratified by CAD status. External validation of findings was undertaken in five cohorts including 7880 cases and 851,152 controls. Results: In the meta-analysis including 4651 cases and 8231 controls the CAD-associated allele at the LPA locus was associated with increased risk of AVS (OR 1.37; 95%CI 1.24–1.52, p = 6.9 × 10−10) with a larger effect size in those without CAD (OR 1.53; 95%CI 1.31–1.79) compared to those with CAD (OR 1.27; 95%CI 1.12–1.45). The CAD-associated allele at 9p21 was associated with a trend towards lower risk of AVS (OR 0.93; 95%CI 0.88–0.99, p = 0.014). External validation confirmed the association of the LPA risk allele with risk of AVS (OR 1.37; 95%CI 1.27–1.47), again with a higher effect size in those without CAD. The small protective effect of the 9p21 CAD risk allele could not be replicated (OR 0.98; 95%CI 0.95–1.02). Conclusions: Our study confirms the association of the LPA locus with risk of AVS, with a higher effect in those without concomitant CAD. Overall, 9p21 was not associated with AVS.

AB - Background: Aortic valve stenosis (AVS) and coronary artery disease (CAD) have a significant genetic contribution and commonly co-exist. To compare and contrast genetic determinants of the two diseases, we investigated associations of the LPA and 9p21 loci, i.e. the two strongest CAD risk loci, with risk of AVS. Methods: We genotyped the CAD-associated variants at the LPA (rs10455872) and 9p21 loci (rs1333049) in the GeneCAST (Genetics of Calcific Aortic STenosis) Consortium and conducted a meta-analysis for their association with AVS. Cases and controls were stratified by CAD status. External validation of findings was undertaken in five cohorts including 7880 cases and 851,152 controls. Results: In the meta-analysis including 4651 cases and 8231 controls the CAD-associated allele at the LPA locus was associated with increased risk of AVS (OR 1.37; 95%CI 1.24–1.52, p = 6.9 × 10−10) with a larger effect size in those without CAD (OR 1.53; 95%CI 1.31–1.79) compared to those with CAD (OR 1.27; 95%CI 1.12–1.45). The CAD-associated allele at 9p21 was associated with a trend towards lower risk of AVS (OR 0.93; 95%CI 0.88–0.99, p = 0.014). External validation confirmed the association of the LPA risk allele with risk of AVS (OR 1.37; 95%CI 1.27–1.47), again with a higher effect size in those without CAD. The small protective effect of the 9p21 CAD risk allele could not be replicated (OR 0.98; 95%CI 0.95–1.02). Conclusions: Our study confirms the association of the LPA locus with risk of AVS, with a higher effect in those without concomitant CAD. Overall, 9p21 was not associated with AVS.

KW - 9p21

KW - Aortic valve stenosis

KW - Lipoprotein (a)

KW - Risk factors

KW - Valvular heart disease

U2 - 10.1016/j.ijcard.2018.11.094

DO - 10.1016/j.ijcard.2018.11.094

M3 - Article

C2 - 30482443

AN - SCOPUS:85057002644

VL - 276

SP - 212

EP - 217

JO - International Journal of Cardiology

JF - International Journal of Cardiology

SN - 0167-5273

ER -