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Genome-wide analysis yields new loci associating with aortic valve stenosis

Helgadottir, Anna; Thorleifsson, Gudmar; Gretarsdottir, Solveig; Stefansson, Olafur A.; Tragante, Vinicius; Thorolfsdottir, Rosa B.; Jonsdottir, Ingileif; Bjornsson, Thorsteinn; Steinthorsdottir, Valgerdur and Verweij, Niek, et al. (2018) In Nature Communications 9(1).
Abstract

Aortic valve stenosis (AS) is the most common valvular heart disease, and valve replacement is the only definitive treatment. Here we report a large genome-wide association (GWA) study of 2,457 Icelandic AS cases and 349,342 controls with a follow-up in up to 4,850 cases and 451,731 controls of European ancestry. We identify two new AS loci, on chromosome 1p21 near PALMD (rs7543130; odds ratio (OR) = 1.20, P = 1.2 × 10-22) and on chromosome 2q22 in TEX41 (rs1830321; OR = 1.15, P = 1.8 × 10-13). Rs7543130 also associates with bicuspid aortic valve (BAV) (OR = 1.28, P = 6.6 × 10-10) and aortic root diameter (P = 1.30 × 10-8), and rs1830321 associates with BAV (OR = 1.12, P = 5.3 ×... (More)

Aortic valve stenosis (AS) is the most common valvular heart disease, and valve replacement is the only definitive treatment. Here we report a large genome-wide association (GWA) study of 2,457 Icelandic AS cases and 349,342 controls with a follow-up in up to 4,850 cases and 451,731 controls of European ancestry. We identify two new AS loci, on chromosome 1p21 near PALMD (rs7543130; odds ratio (OR) = 1.20, P = 1.2 × 10-22) and on chromosome 2q22 in TEX41 (rs1830321; OR = 1.15, P = 1.8 × 10-13). Rs7543130 also associates with bicuspid aortic valve (BAV) (OR = 1.28, P = 6.6 × 10-10) and aortic root diameter (P = 1.30 × 10-8), and rs1830321 associates with BAV (OR = 1.12, P = 5.3 × 10-3) and coronary artery disease (OR = 1.05, P = 9.3 × 10-5). The results implicate both cardiac developmental abnormalities and atherosclerosis-like processes in the pathogenesis of AS. We show that several pathways are shared by CAD and AS. Causal analysis suggests that the shared risk factors of Lp(a) and non-high-density lipoprotein cholesterol contribute substantially to the frequent co-occurence of these diseases.

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Nature Communications
volume
9
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1
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Nature Publishing Group
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  • scopus:85043290754
ISSN
2041-1723
DOI
10.1038/s41467-018-03252-6
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English
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55c08a87-7fa3-434a-8886-b46460dc7268
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2018-03-19 14:11:50
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@article{55c08a87-7fa3-434a-8886-b46460dc7268,
  abstract     = {<p>Aortic valve stenosis (AS) is the most common valvular heart disease, and valve replacement is the only definitive treatment. Here we report a large genome-wide association (GWA) study of 2,457 Icelandic AS cases and 349,342 controls with a follow-up in up to 4,850 cases and 451,731 controls of European ancestry. We identify two new AS loci, on chromosome 1p21 near PALMD (rs7543130; odds ratio (OR) = 1.20, P = 1.2 × 10<sup>-22</sup>) and on chromosome 2q22 in TEX41 (rs1830321; OR = 1.15, P = 1.8 × 10<sup>-13</sup>). Rs7543130 also associates with bicuspid aortic valve (BAV) (OR = 1.28, P = 6.6 × 10<sup>-10</sup>) and aortic root diameter (P = 1.30 × 10<sup>-8</sup>), and rs1830321 associates with BAV (OR = 1.12, P = 5.3 × 10<sup>-3</sup>) and coronary artery disease (OR = 1.05, P = 9.3 × 10<sup>-5</sup>). The results implicate both cardiac developmental abnormalities and atherosclerosis-like processes in the pathogenesis of AS. We show that several pathways are shared by CAD and AS. Causal analysis suggests that the shared risk factors of Lp(a) and non-high-density lipoprotein cholesterol contribute substantially to the frequent co-occurence of these diseases.</p>},
  articleno    = {987},
  author       = {Helgadottir, Anna and Thorleifsson, Gudmar and Gretarsdottir, Solveig and Stefansson, Olafur A. and Tragante, Vinicius and Thorolfsdottir, Rosa B. and Jonsdottir, Ingileif and Bjornsson, Thorsteinn and Steinthorsdottir, Valgerdur and Verweij, Niek and Nielsen, Jonas B. and Zhou, Wei and Folkersen, Lasse and Martinsson, Andreas and Heydarpour, Mahyar and Prakash, Siddharth and Oskarsson, Gylfi and Gudbjartsson, Tomas and Geirsson, Arnar and Olafsson, Isleifur and Sigurdsson, Emil L. and Almgren, Peter and Melander, Olle and Franco-Cereceda, Anders and Hamsten, Anders and Fritsche, Lars and Lin, Maoxuan and Yang, Bo and Hornsby, Whitney and Guo, Dongchuan and Brummett, Chad M. and Abecasis, Gonçalo and Mathis, Michael and Milewicz, Dianna and Body, Simon C. and Eriksson, Per and Willer, Cristen J. and Hveem, Kristian and Newton-Cheh, Christopher and Smith, J. Gustav and Danielsen, Ragnar and Thorgeirsson, Gudmundur and Thorsteinsdottir, Unnur and Gudbjartsson, Daniel F. and Holm, Hilma and Stefansson, Kari},
  issn         = {2041-1723},
  language     = {eng},
  month        = {12},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Genome-wide analysis yields new loci associating with aortic valve stenosis},
  url          = {http://dx.doi.org/10.1038/s41467-018-03252-6},
  volume       = {9},
  year         = {2018},
}