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

• Published in: European heart journal 2021-11, Vol.42 (44), p.4523-4534
• Main Authors: Ahlberg, Gustav, Andreasen, Laura, Ghouse, Jonas, Bertelsen, Litten, Bundgaard, Henning, Haunsø, Stig, Svendsen, Jesper H, Olesen, Morten S
• Format: Article
• Language: English
• Subjects: Atrial Appendage; Atrial Fibrillation - genetics; Atrial Function, Left; Clinical Research; Genome-Wide Association Study; Heart Atria - diagnostic imaging; Humans; Prospective Studies
• ISSN: 0195-668X; 1522-9645
• DOI: 10.1093/eurheartj/ehab466

Abstract 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. Graphical Abstract Genome-wide association study on left atrial volume and function based on cardiac magnetic resonance imaging. Imaging data from 35 658 individuals were exposed to machine learning algorithms to annotate five left atrial traits. A total of 18 novel genetic loci were associated with left atrial volume and function. Of these, 15 constituted unique loci. Genes marked with bold have previously been associated with cardiomyopathy.