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

Anna Helgadóttir; Guðmar Þorleifsson; Sólveig Grétarsdóttir; Ólafur Andri Stefánsson; Vinicius Tragante; Rósa B. Þórólfsdóttir; Ingileif Jónsdóttir; Þorsteinn Björnsson; Valgerður Steinthórsdóttir; Niek Verweij; Jonas Bille Nielsen; Wei Zhou; Lasse Folkersen; Andreas Martinsson; Mahyar Heydarpour; Siddharth K. Prakash; Gylfi Óskarsson; Tómas Guðbjartsson; Arnar Geirsson; Ísleifur Ólafsson; Emil L. Sigurdsson; Peter Almgren; Olle Melander; Anders Franco‐Cereceda; Anders Hamsten; Lars G. Fritsche; Maoxuan Lin; Bo Yang; Whitney Hornsby; Dongchuan Guo

doi:10.1038/s41467-018-03252-6

GeneticsNature CommunicationsMar 1, 2018

Peer-reviewed journal article

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

Anna Helgadóttir iD, Guðmar Þorleifsson iD, Sólveig Grétarsdóttir iD, Ólafur Andri Stefánsson iD, Vinicius Tragante iD, Rósa B. Þórólfsdóttir iD, Ingileif Jónsdóttir iD, Þorsteinn Björnsson, Valgerður Steinthórsdóttir iD, Niek Verweij iD, Jonas Bille Nielsen iD, Wei Zhou iD, Lasse Folkersen iD, Andreas Martinsson iD, Mahyar Heydarpour iD, Siddharth K. Prakash iD, Gylfi Óskarsson iD, Tómas Guðbjartsson iD, Arnar Geirsson iD, Ísleifur Ólafsson iD, Emil L. Sigurdsson, Peter Almgren iD, Olle Melander iD, Anders Franco‐Cereceda iD, Anders Hamsten iD, , Kāri Stefánsson iD

Abstract

Aortic valve stenosis (AS) is the most common valvular heart disease, characterized by a thickened and calcified valve causing left ventricular outflow obstruction. Severe AS is a significant cause of morbidity and mortality, affecting approximately 5% of those over 70 years of age1,2,3. Little is known about the genetics of AS, although recently a variant at the LPA locus4 and a rare MYH6 missense variant were found to associate with AS5. We report a large genome-wide association study (GWAS) with a follow-up in up to 7,307 AS cases and 801,073 controls. We identified two new AS loci, on chromosome 1p21 near PALMD (rs7543130; OR=1.20, P=1.2x10-22) and on chromosome 2q22 in TEX41 (rs1830321; OR=1.15, P=1.8x10-13). Rs7543130 also associates with bicuspid aortic valve (BAV) (OR=1.28, P=6.6x10-10) and aortic root diameter (P=1.30x10-8) and rs1830321 associates with BAV (OR=1.12, P=5.3x10-3 and coronary artery disease (CAD) (OR=1.05, P=9.3x10-5). These results indicate that AS is partly rooted in the same processes as cardiac development and atherosclerosis.

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