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
SN - 0167-5273
VL - 276
SP - 212
EP - 217
JO - International Journal of Cardiology
JF - International Journal of Cardiology
ER -