The Genetic Determinants of Aortic Distention

James P Pirruccello; Joel T Rämö; Seung Hoan Choi; Mark D Chaffin; Shinwan Kany; Mahan Nekoui; Elizabeth L Chou; Sean J Jurgens; Samuel F Friedman; Dejan Juric; James R Stone; Puneet Batra; Kenney Ng; Anthony A Philippakis; Mark E Lindsay; Patrick T Ellinor

doi:10.1016/j.jacc.2023.01.044

The Genetic Determinants of Aortic Distention

Standard

The Genetic Determinants of Aortic Distention. / Pirruccello, James P; Rämö, Joel T; Choi, Seung Hoan; Chaffin, Mark D; Kany, Shinwan; Nekoui, Mahan; Chou, Elizabeth L; Jurgens, Sean J; Friedman, Samuel F; Juric, Dejan; Stone, James R; Batra, Puneet; Ng, Kenney; Philippakis, Anthony A; Lindsay, Mark E; Ellinor, Patrick T.

In: J AM COLL CARDIOL, Vol. 81, No. 14, 11.04.2023, p. 1320-1335.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Pirruccello, JP, Rämö, JT, Choi, SH, Chaffin, MD, Kany, S, Nekoui, M, Chou, EL, Jurgens, SJ, Friedman, SF, Juric, D, Stone, JR, Batra, P, Ng, K, Philippakis, AA, Lindsay, ME & Ellinor, PT 2023, 'The Genetic Determinants of Aortic Distention', J AM COLL CARDIOL, vol. 81, no. 14, pp. 1320-1335. https://doi.org/10.1016/j.jacc.2023.01.044

APA

Pirruccello, J. P., Rämö, J. T., Choi, S. H., Chaffin, M. D., Kany, S., Nekoui, M., Chou, E. L., Jurgens, S. J., Friedman, S. F., Juric, D., Stone, J. R., Batra, P., Ng, K., Philippakis, A. A., Lindsay, M. E., & Ellinor, P. T. (2023). The Genetic Determinants of Aortic Distention. J AM COLL CARDIOL, 81(14), 1320-1335. https://doi.org/10.1016/j.jacc.2023.01.044

Vancouver

Pirruccello JP, Rämö JT, Choi SH, Chaffin MD, Kany S, Nekoui M et al. The Genetic Determinants of Aortic Distention. J AM COLL CARDIOL. 2023 Apr 11;81(14):1320-1335. https://doi.org/10.1016/j.jacc.2023.01.044

Bibtex

@article{8ff01c701daf4fe6a89d28f06ebb79c1,

title = "The Genetic Determinants of Aortic Distention",

abstract = "BACKGROUND: As the largest conduit vessel, the aorta is responsible for the conversion of phasic systolic inflow from ventricular ejection into more continuous peripheral blood delivery. Systolic distention and diastolic recoil conserve energy and are enabled by the specialized composition of the aortic extracellular matrix. Aortic distensibility decreases with age and vascular disease.OBJECTIVES: In this study, we sought to discover epidemiologic correlates and genetic determinants of aortic distensibility and strain.METHODS: We trained a deep learning model to quantify thoracic aortic area throughout the cardiac cycle from cardiac magnetic resonance images and calculated aortic distensibility and strain in 42,342 UK Biobank participants.RESULTS: Descending aortic distensibility was inversely associated with future incidence of cardiovascular diseases, such as stroke (HR: 0.59 per SD; P = 0.00031). The heritabilities of aortic distensibility and strain were 22% to 25% and 30% to 33%, respectively. Common variant analyses identified 12 and 26 loci for ascending and 11 and 21 loci for descending aortic distensibility and strain, respectively. Of the newly identified loci, 22 were not significantly associated with thoracic aortic diameter. Nearby genes were involved in elastogenesis and atherosclerosis. Aortic strain and distensibility polygenic scores had modest effect sizes for predicting cardiovascular outcomes (delaying or accelerating disease onset by 2%-18% per SD change in scores) and remained statistically significant predictors after accounting for aortic diameter polygenic scores.CONCLUSIONS: Genetic determinants of aortic function influence risk for stroke and coronary artery disease and may lead to novel targets for medical intervention.",

keywords = "Humans, Aorta, Thoracic, Aorta, Aortic Diseases/pathology, Magnetic Resonance Imaging, Stroke",

author = "Pirruccello, {James P} and R{\"a}m{\"o}, {Joel T} and Choi, {Seung Hoan} and Chaffin, {Mark D} and Shinwan Kany and Mahan Nekoui and Chou, {Elizabeth L} and Jurgens, {Sean J} and Friedman, {Samuel F} and Dejan Juric and Stone, {James R} and Puneet Batra and Kenney Ng and Philippakis, {Anthony A} and Lindsay, {Mark E} and Ellinor, {Patrick T}",

year = "2023",

month = apr,

day = "11",

doi = "10.1016/j.jacc.2023.01.044",

language = "English",

volume = "81",

pages = "1320--1335",

journal = "J AM COLL CARDIOL",

issn = "0735-1097",

publisher = "Elsevier USA",

number = "14",

}

RIS

TY - JOUR

T1 - The Genetic Determinants of Aortic Distention

AU - Pirruccello, James P

AU - Rämö, Joel T

AU - Choi, Seung Hoan

AU - Chaffin, Mark D

AU - Kany, Shinwan

AU - Nekoui, Mahan

AU - Chou, Elizabeth L

AU - Jurgens, Sean J

AU - Friedman, Samuel F

AU - Juric, Dejan

AU - Stone, James R

AU - Batra, Puneet

AU - Ng, Kenney

AU - Philippakis, Anthony A

AU - Lindsay, Mark E

AU - Ellinor, Patrick T

PY - 2023/4/11

Y1 - 2023/4/11

N2 - BACKGROUND: As the largest conduit vessel, the aorta is responsible for the conversion of phasic systolic inflow from ventricular ejection into more continuous peripheral blood delivery. Systolic distention and diastolic recoil conserve energy and are enabled by the specialized composition of the aortic extracellular matrix. Aortic distensibility decreases with age and vascular disease.OBJECTIVES: In this study, we sought to discover epidemiologic correlates and genetic determinants of aortic distensibility and strain.METHODS: We trained a deep learning model to quantify thoracic aortic area throughout the cardiac cycle from cardiac magnetic resonance images and calculated aortic distensibility and strain in 42,342 UK Biobank participants.RESULTS: Descending aortic distensibility was inversely associated with future incidence of cardiovascular diseases, such as stroke (HR: 0.59 per SD; P = 0.00031). The heritabilities of aortic distensibility and strain were 22% to 25% and 30% to 33%, respectively. Common variant analyses identified 12 and 26 loci for ascending and 11 and 21 loci for descending aortic distensibility and strain, respectively. Of the newly identified loci, 22 were not significantly associated with thoracic aortic diameter. Nearby genes were involved in elastogenesis and atherosclerosis. Aortic strain and distensibility polygenic scores had modest effect sizes for predicting cardiovascular outcomes (delaying or accelerating disease onset by 2%-18% per SD change in scores) and remained statistically significant predictors after accounting for aortic diameter polygenic scores.CONCLUSIONS: Genetic determinants of aortic function influence risk for stroke and coronary artery disease and may lead to novel targets for medical intervention.

AB - BACKGROUND: As the largest conduit vessel, the aorta is responsible for the conversion of phasic systolic inflow from ventricular ejection into more continuous peripheral blood delivery. Systolic distention and diastolic recoil conserve energy and are enabled by the specialized composition of the aortic extracellular matrix. Aortic distensibility decreases with age and vascular disease.OBJECTIVES: In this study, we sought to discover epidemiologic correlates and genetic determinants of aortic distensibility and strain.METHODS: We trained a deep learning model to quantify thoracic aortic area throughout the cardiac cycle from cardiac magnetic resonance images and calculated aortic distensibility and strain in 42,342 UK Biobank participants.RESULTS: Descending aortic distensibility was inversely associated with future incidence of cardiovascular diseases, such as stroke (HR: 0.59 per SD; P = 0.00031). The heritabilities of aortic distensibility and strain were 22% to 25% and 30% to 33%, respectively. Common variant analyses identified 12 and 26 loci for ascending and 11 and 21 loci for descending aortic distensibility and strain, respectively. Of the newly identified loci, 22 were not significantly associated with thoracic aortic diameter. Nearby genes were involved in elastogenesis and atherosclerosis. Aortic strain and distensibility polygenic scores had modest effect sizes for predicting cardiovascular outcomes (delaying or accelerating disease onset by 2%-18% per SD change in scores) and remained statistically significant predictors after accounting for aortic diameter polygenic scores.CONCLUSIONS: Genetic determinants of aortic function influence risk for stroke and coronary artery disease and may lead to novel targets for medical intervention.

KW - Humans

KW - Aorta, Thoracic

KW - Aorta

KW - Aortic Diseases/pathology

KW - Magnetic Resonance Imaging

KW - Stroke

U2 - 10.1016/j.jacc.2023.01.044

DO - 10.1016/j.jacc.2023.01.044

M3 - SCORING: Journal article

C2 - 37019578

VL - 81

SP - 1320

EP - 1335

JO - J AM COLL CARDIOL

JF - J AM COLL CARDIOL

SN - 0735-1097

IS - 14

ER -