TY - JOUR

T1 - Genome-wide association study identifies 18 novel loci associated with left atrial volume and function

AU - Ahlberg, Gustav

AU - Andreasen, Laura

AU - Ghouse, Jonas

AU - Bertelsen, Litten

AU - Bundgaard, Henning

AU - Haunsø, Stig

AU - Svendsen, Jesper H

AU - Olesen, Morten S

N1 - © The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

PY - 2021

Y1 - 2021

N2 - AIMS : Left atrial (LA) volume and function impose significant impact on cardiovascular pathogenesis if compromised. We aimed at investigating the genetic architecture of LA volume and function using cardiac magnetic resonance imaging data.METHODS AND RESULTS : We used the UK Biobank, which is a large prospective population study with available phenotypic and genetic data. On a subset of 35 658 European individuals, we performed genome-wide association studies on five volumetric and functional LA variables, generated using a machine learning algorithm. In total, we identified 18 novel genetic loci, mapped to genes with known roles in cardiomyopathy (e.g. MYO18B, TTN, DSP, ANKRD1) and arrhythmia (e.g. TTN, CASQ2, MYO18B, C9orf3). We observed high genetic correlation between LA volume and function and stroke, which was most pronounced for LA passive emptying fraction (rg = 0.40, P = 4 × 10-6). To investigate whether the genetic risk of atrial fibrillation (AF) is associated with LA traits that precede overt AF, we produced a polygenetic risk score for AF. We found that polygenetic risk for AF is associated with increased LA volume and decreased LA function in participants without AF [LAmax 0.25 (mL/m2)/standard deviation (SD), 95% confidence interval (CI) (0.15; 0.36), P = 5.13 × 10-6; LAmin 0.21 (mL/m2)/SD, 95% CI (0.15; 0.28), P = 1.86 × 10-10; LA active emptying fraction -0.35%/SD, 95% CI (-0.43; -0.26), P = 3.14 × 10-14].CONCLUSION : We report on 18 genetic loci associated with LA volume and function and show evidence for several plausible candidate genes important for LA structure.

AB - AIMS : Left atrial (LA) volume and function impose significant impact on cardiovascular pathogenesis if compromised. We aimed at investigating the genetic architecture of LA volume and function using cardiac magnetic resonance imaging data.METHODS AND RESULTS : We used the UK Biobank, which is a large prospective population study with available phenotypic and genetic data. On a subset of 35 658 European individuals, we performed genome-wide association studies on five volumetric and functional LA variables, generated using a machine learning algorithm. In total, we identified 18 novel genetic loci, mapped to genes with known roles in cardiomyopathy (e.g. MYO18B, TTN, DSP, ANKRD1) and arrhythmia (e.g. TTN, CASQ2, MYO18B, C9orf3). We observed high genetic correlation between LA volume and function and stroke, which was most pronounced for LA passive emptying fraction (rg = 0.40, P = 4 × 10-6). To investigate whether the genetic risk of atrial fibrillation (AF) is associated with LA traits that precede overt AF, we produced a polygenetic risk score for AF. We found that polygenetic risk for AF is associated with increased LA volume and decreased LA function in participants without AF [LAmax 0.25 (mL/m2)/standard deviation (SD), 95% confidence interval (CI) (0.15; 0.36), P = 5.13 × 10-6; LAmin 0.21 (mL/m2)/SD, 95% CI (0.15; 0.28), P = 1.86 × 10-10; LA active emptying fraction -0.35%/SD, 95% CI (-0.43; -0.26), P = 3.14 × 10-14].CONCLUSION : We report on 18 genetic loci associated with LA volume and function and show evidence for several plausible candidate genes important for LA structure.

U2 - 10.1093/eurheartj/ehab466

DO - 10.1093/eurheartj/ehab466

M3 - Journal article

C2 - 34338756

VL - 42

SP - 4523

EP - 4534

JO - European Heart Journal

JF - European Heart Journal

SN - 0195-668X

IS - 44

ER -