Genome-wide association analysis of left ventricular imaging-derived phenotypes identifies 72 risk loci and yields genetic insights into hypertrophic cardiomyopathy

• Published in: Nature communications Vol. 14; no. 1; pp. 7900 - 15
• Main Authors: Ning, Caibo, Fan, Linyun, Jin, Meng, Wang, Wenji, Hu, Zhiqiang, Cai, Yimin, Chen, Liangkai, Lu, Zequn, Zhang, Ming, Chen, Can, Li, Yanmin, Zhang, Fuwei, Wang, Wenzhuo, Liu, Yizhuo, Chen, Shuoni, Jiang, Yuan, He, Chunyi, Wang, Zhuo, Chen, Xu, Li, Hanting, Li, Gaoyuan, Ma, Qianying, Geng, Hui, Tian, Wen, Zhang, Heng, Liu, Bo, Xia, Qing, Yang, Xiaojun, Liu, Zhongchun, Li, Bin, Zhu, Ying, Li, Xiangpan, Zhang, Shaoting, Tian, Jianbo, Miao, Xiaoping
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.11.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 45/43; 59/57; 692/4019/592/2727; 692/4019/592/75/74/1540; 692/53/2423; 692/700/1421/1628; Algorithms; Association analysis; Cardiomyopathy; Cardiomyopathy, Hypertrophic - diagnostic imaging; Cardiomyopathy, Hypertrophic - genetics; Cardiovascular diseases; Deep learning; Gene loci; Genome-wide association studies; Genome-Wide Association Study; Genomes; Heart; Heart Ventricles - pathology; Humanities and Social Sciences; Humans; Machine learning; Magnetic resonance; Magnetic resonance imaging; Morbidity; Mortality; multidisciplinary; Phenotype; Phenotypes; Polygenic inheritance; Population genetics; Risk; Science; Science (multidisciplinary); Systole; Technology assessment; Thickness; Ventricle
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-43771-5

Left ventricular regional wall thickness (LVRWT) is an independent predictor of morbidity and mortality in cardiovascular diseases (CVDs). To identify specific genetic influences on individual LVRWT, we established a novel deep learning algorithm to calculate 12 LVRWTs accurately in 42,194 individuals from the UK Biobank with cardiac magnetic resonance (CMR) imaging. Genome-wide association studies of CMR-derived 12 LVRWTs identified 72 significant genetic loci associated with at least one LVRWT phenotype ( P  < 5 × 10 −8 ), which were revealed to actively participate in heart development and contraction pathways. Significant causal relationships were observed between the LVRWT traits and hypertrophic cardiomyopathy (HCM) using genetic correlation and Mendelian randomization analyses ( P  < 0.01). The polygenic risk score of inferoseptal LVRWT at end systole exhibited a notable association with incident HCM, facilitating the identification of high-risk individuals. The findings yield insights into the genetic determinants of LVRWT phenotypes and shed light on the biological basis for HCM etiology. Changes of left ventricular structure are used to predict morbidity and mortality in cardiovascular diseases. Here the authors conducted a study using advanced deep learning technology to analyze left ventricular regional wall thickness (LVRWT) in a large population, identifying 72 significant genetic loci linked to LVRWT traits.