Fig. 4: PGS associate with HCM risk and adverse outcomes in relatives of HCM cases.
To evaluate applications of PGS in families undergoing screening and surveillance for HCM, we studied the relatives of HCM cases in two cohorts, GeL and EMC cohort. a, OR for HCM among relatives of HCM probands in the two cohorts (GeL, n = 288; EMC, n = 214), stratified by PGS. b, Violin and box and whisker plot of maxLVWT in sarcomere-positive relatives stratified by highest (n = 40) and lowest (n = 38) PGSEMC quintiles. Box plot indicate median and interquartile range, whiskers denote 1.5× the interquartile range, outliers shown separately, and the edges of violin plots indicate minimum and maximum values. Dashed line indicates a 13-mm cutoff used for guideline diagnosis of HCM in relatives of individuals with HCM. c, Cumulative major adverse cardiovascular events (MACE) among 214 sarcomere-positive relatives of HCM index patients stratified by PGSEMC above or below the median. MACE was defined as a composite of septal reduction therapy, cardiac transplantation, aborted cardiac arrest, appropriate defibrillator shock or sudden cardiac death. To avoid inflation of PGS performance resulting from sample overlap, PGS were rederived from GWAS leaving out the cohort that the PGS was being evaluated in (GeL–PGSGeL, EMC–PGSEMC). HR calculated using Cox proportional hazards model, adjusted for sex, first four genetic PCs, and genetic relatedness matrix, with two-sided P value.
