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

Anna Helgadottir; Gudmar Thorleifsson; Solveig Gretarsdottir; Olafur A Stefansson; Vinicius Tragante; Rosa B Thorolfsdottir; Ingileif Jonsdottir; Thorsteinn Bjornsson; Valgerdur Steinthorsdottir; Niek Verweij; Jonas B Nielsen; Wei Zhou; Lasse Folkersen; Andreas Martinsson; Mahyar Heydarpour; Siddharth Prakash; Gylfi Oskarsson; Tomas Gudbjartsson; Arnar Geirsson; Isleifur Olafsson; Emil L Sigurdsson; Peter Almgren; Olle Melander; Anders Franco-Cereceda; Anders Hamsten; Lars Fritsche; Maoxuan Lin; Bo Yang; Whitney Hornsby; Dongchuan Guo; Chad M Brummett; Gonçalo Abecasis; Michael Mathis; Dianna Milewicz; Simon C Body; Per Eriksson; Cristen J Willer; Kristian Hveem; Christopher Newton-Cheh; J Gustav Smith; Ragnar Danielsen; Gudmundur Thorgeirsson; Unnur Thorsteinsdottir; Daniel F Gudbjartsson; Hilma Holm; Kari Stefansson

doi:10.1038/s41467-018-03252-6

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

Anna Helgadottir, Gudmar Thorleifsson, Solveig Gretarsdottir, Olafur A Stefansson, Vinicius Tragante, Rosa B Thorolfsdottir, Ingileif Jonsdottir, Thorsteinn Bjornsson, Valgerdur Steinthorsdottir, Niek Verweij, Jonas B Nielsen, Wei Zhou, Lasse Folkersen, Andreas Martinsson, Mahyar Heydarpour, Siddharth Prakash, Gylfi Oskarsson, Tomas Gudbjartsson, Arnar Geirsson, Isleifur OlafssonEmil L Sigurdsson, Peter Almgren, Olle Melander, Anders Franco-Cereceda, Anders Hamsten, Lars Fritsche, Maoxuan Lin, Bo Yang, Whitney Hornsby, Dongchuan Guo, Chad M Brummett, Gonçalo Abecasis, Michael Mathis, Dianna Milewicz, Simon C Body, Per Eriksson, Cristen J Willer, Kristian Hveem, Christopher Newton-Cheh, J Gustav Smith, Ragnar Danielsen, Gudmundur Thorgeirsson, Unnur Thorsteinsdottir, Daniel F Gudbjartsson, Hilma Holm, Kari Stefansson

Psykiatrisk Center Sct. Hans

92 Citationer (Scopus)

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 × 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.

Originalsprog	Engelsk
Tidsskrift	Nature Communications
Vol/bind	9
Udgave nummer	1
Sider (fra-til)	987
ISSN	2041-1722
DOI	https://doi.org/10.1038/s41467-018-03252-6
Status	Udgivet - 7 mar. 2018

Adgang til dokumentet

10.1038/s41467-018-03252-6

Citationsformater

Helgadottir, A., Thorleifsson, G., Gretarsdottir, S., Stefansson, O. A., Tragante, V., Thorolfsdottir, R. B., Jonsdottir, I., Bjornsson, T., Steinthorsdottir, V., Verweij, N., Nielsen, J. B., Zhou, W., Folkersen, L., Martinsson, A., Heydarpour, M., Prakash, S., Oskarsson, G., Gudbjartsson, T., Geirsson, A., ... Stefansson, K. (2018). Genome-wide analysis yields new loci associating with aortic valve stenosis. Nature Communications, 9(1), 987. https://doi.org/10.1038/s41467-018-03252-6

Helgadottir, A, Thorleifsson, G, Gretarsdottir, S, Stefansson, OA, Tragante, V, Thorolfsdottir, RB, Jonsdottir, I, Bjornsson, T, Steinthorsdottir, V, Verweij, N, Nielsen, JB, Zhou, W, Folkersen, L, Martinsson, A, Heydarpour, M, Prakash, S, Oskarsson, G, Gudbjartsson, T, Geirsson, A, Olafsson, I, Sigurdsson, EL, Almgren, P, Melander, O, Franco-Cereceda, A, Hamsten, A, Fritsche, L, Lin, M, Yang, B, Hornsby, W, Guo, D, Brummett, CM, Abecasis, G, Mathis, M, Milewicz, D, Body, SC, Eriksson, P, Willer, CJ, Hveem, K, Newton-Cheh, C, Smith, JG, Danielsen, R, Thorgeirsson, G, Thorsteinsdottir, U, Gudbjartsson, DF, Holm, H & Stefansson, K 2018, 'Genome-wide analysis yields new loci associating with aortic valve stenosis', Nature Communications, bind 9, nr. 1, s. 987. https://doi.org/10.1038/s41467-018-03252-6

@article{b5662bb301bc4369939b9f5e5ce50181,

title = "Genome-wide analysis yields new loci associating with aortic valve stenosis",

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 × 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.",

author = "Anna Helgadottir and Gudmar Thorleifsson and Solveig Gretarsdottir and Stefansson, {Olafur A} and Vinicius Tragante and Thorolfsdottir, {Rosa B} and Ingileif Jonsdottir and Thorsteinn Bjornsson and Valgerdur Steinthorsdottir and Niek Verweij and Nielsen, {Jonas B} and Wei Zhou and Lasse Folkersen and Andreas Martinsson and Mahyar Heydarpour and Siddharth Prakash and Gylfi Oskarsson and Tomas Gudbjartsson and Arnar Geirsson and Isleifur Olafsson and Sigurdsson, {Emil L} and Peter Almgren and Olle Melander and Anders Franco-Cereceda and Anders Hamsten and Lars Fritsche and Maoxuan Lin and Bo Yang and Whitney Hornsby and Dongchuan Guo and Brummett, {Chad M} and Gon{\c c}alo Abecasis and Michael Mathis and Dianna Milewicz and Body, {Simon C} and Per Eriksson and Willer, {Cristen J} and Kristian Hveem and Christopher Newton-Cheh and Smith, {J Gustav} and Ragnar Danielsen and Gudmundur Thorgeirsson and Unnur Thorsteinsdottir and Gudbjartsson, {Daniel F} and Hilma Holm and Kari Stefansson",

year = "2018",

month = mar,

day = "7",

doi = "10.1038/s41467-018-03252-6",

language = "English",

volume = "9",

pages = "987",

journal = "Nature Communications",

issn = "2041-1722",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Genome-wide analysis yields new loci associating with aortic valve stenosis

AU - Helgadottir, Anna

AU - Thorleifsson, Gudmar

AU - Gretarsdottir, Solveig

AU - Stefansson, Olafur A

AU - Tragante, Vinicius

AU - Thorolfsdottir, Rosa B

AU - Jonsdottir, Ingileif

AU - Bjornsson, Thorsteinn

AU - Steinthorsdottir, Valgerdur

AU - Verweij, Niek

AU - Nielsen, Jonas B

AU - Zhou, Wei

AU - Folkersen, Lasse

AU - Martinsson, Andreas

AU - Heydarpour, Mahyar

AU - Prakash, Siddharth

AU - Oskarsson, Gylfi

AU - Gudbjartsson, Tomas

AU - Geirsson, Arnar

AU - Olafsson, Isleifur

AU - Sigurdsson, Emil L

AU - Almgren, Peter

AU - Melander, Olle

AU - Franco-Cereceda, Anders

AU - Hamsten, Anders

AU - Fritsche, Lars

AU - Lin, Maoxuan

AU - Yang, Bo

AU - Hornsby, Whitney

AU - Guo, Dongchuan

AU - Brummett, Chad M

AU - Abecasis, Gonçalo

AU - Mathis, Michael

AU - Milewicz, Dianna

AU - Body, Simon C

AU - Eriksson, Per

AU - Willer, Cristen J

AU - Hveem, Kristian

AU - Newton-Cheh, Christopher

AU - Smith, J Gustav

AU - Danielsen, Ragnar

AU - Thorgeirsson, Gudmundur

AU - Thorsteinsdottir, Unnur

AU - Gudbjartsson, Daniel F

AU - Holm, Hilma

AU - Stefansson, Kari

PY - 2018/3/7

Y1 - 2018/3/7

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-018-03252-6

DO - 10.1038/s41467-018-03252-6

M3 - Journal article

C2 - 29511194

SN - 2041-1722

VL - 9

SP - 987

JO - Nature Communications

JF - Nature Communications

IS - 1

ER -

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

Abstract

Adgang til dokumentet

Fingeraftryk

Citationsformater