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Mosley JD, Levinson RT, Farber-Eger E, Edwards TL, Hellwege JN, Hung AM, Giri A, Shuey MM, Shaffer CM, Shi M, Brittain EL, Chung WK, Kullo IJ, Arruda-Olson AM, Jarvik GP, Larson EB, Crosslin DR, Williams MS, Borthwick KM, Hakonarson H, Denny JC, Wang TJ, Stein CM, Roden DM, Wells QS. The polygenic architecture of left ventricular mass mirrors the clinical epidemiology. Scientific reports. 2020 May 5;10(10). 7561 p.
Abstract
Left ventricular (LV) mass is a prognostic biomarker for incident heart disease and all-cause mortality. Large-scale genome-wide association studies have identified few SNPs associated with LV mass. We hypothesized that a polygenic discovery approach using LV mass measurements made in a clinical population would identify risk factors and diseases associated with adverse LV remodeling. We developed a polygenic single nucleotide polymorphism-based predictor of LV mass in 7,601 individuals with LV mass measurements made during routine clinical care. We tested for associations between this predictor and 894 clinical diagnoses measured in 58,838 unrelated genotyped individuals. There were 29 clinical phenotypes associated with the LV mass genetic predictor at FDR q