PT - JOURNAL ARTICLE AU - James P. Pirruccello AU - Alexander Bick AU - Minxian Wang AU - Mark Chaffin AU - Steven A. Lubitz AU - Patrick T. Ellinor AU - Amit V Khera AU - Sekar Kathiresan AU - Krishna G. Aragam TI - Analysis of cardiac magnetic resonance imaging traits in 29,000 individuals reveals shared genetic basis with dilated cardiomyopathy AID - 10.1101/2020.02.12.946038 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.02.12.946038 4099 - http://biorxiv.org/content/early/2020/02/13/2020.02.12.946038.short 4100 - http://biorxiv.org/content/early/2020/02/13/2020.02.12.946038.full AB - Dilated cardiomyopathy (DCM) is an important cause of heart failure and the leading indication for heart transplantation. Many rare genetic variants have been associated with DCM, but common variant studies of the disease have yielded few associated loci. As structural changes in the heart are a defining feature of DCM, we conducted a genome-wide association study (GWAS) of cardiac magnetic resonance imaging (MRI)-derived left ventricular measurements in 29,041 UK Biobank participants. 26 novel loci were associated with cardiac structure and function. These loci were found near 17 genes previously shown to cause Mendelian cardiomyopathies. A polygenic score of left ventricular end systolic volume was associated with incident DCM in previously disease-free individuals (hazard ratio = 1.54 per one standard deviation increase in the polygenic score, P = 2.1×10−16). Even among carriers of truncating mutations in TTN, the polygenic score influenced the size and function of the heart. These results further implicate common genetic polymorphisms in DCM pathogenesis.