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

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title = "Effects of the coronary artery disease associated LPA and 9p21 loci on risk of aortic valve stenosis",
abstract = "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.",
keywords = "9p21, Aortic valve stenosis, Lipoprotein (a), Risk factors, Valvular heart disease",
author = "Teresa Trenkwalder and Nelson, {Christopher P.} and Musameh, {Muntaser D.} and Mordi, {Ify R.} and Thorsten Kessler and Costanza Pellegrini and Radoslaw Debiec and Tobias Rheude and Viktor Lazovic and Lingyao Zeng and Andreas Martinsson and {Gustav Smith}, J. and G{\aa}din, {Jesper R.} and Anders Franco-Cereceda and Per Eriksson and Nielsen, {Jonas B.} and Graham, {Sarah E.} and Willer, {Cristen J.} and Kristian Hveem and Adnan Kastrati and Braund, {Peter S.} and Palmer, {Colin N.A.} and Amparo Aracil and Oliver Husser and Wolfgang Koenig and Heribert Schunkert and Lang, {Chim C.} and Christian Hengstenberg and Samani, {Nilesh J.}",
year = "2019",
month = feb,
doi = "10.1016/j.ijcard.2018.11.094",
language = "English",
volume = "276",
pages = "212--217",
journal = "International Journal of Cardiology",
issn = "0167-5273",
publisher = "Elsevier",