Polygenic Risk Scores and Coronary Artery Disease

Name: Work Video:
Duration: 3 min 30 s
Michael G. Levin; Daniel J. Rader
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3432], '(GWAS),': [214], 'into': [215, 2133, 2232], 'simplified': [216], 'that': [218, 299, 697, 784, 1039, 1241, 1531, 1559, 1579, 2043, 2285], 'can': [219, 552, 572, 615, 1633, 2044], 'be': [220, 554, 617, 704, 728, 1535, 1590, 1634, 1812, 1834, 1872, 1949, 1961, 2046, 2141, 2152, 2240, 2291], 'used': [221, 1591, 2047, 2185], 'prediction.': [224, 352], 'The': [225, 353, 526, 875, 1503, 2978], 'first': [226, 354, 1696], 'GWAS': [227, 903, 919, 940, 1675, 1688, 1709], 'coronary': [229, 1375, 2414, 2559, 2613, 2705, 2814, 2951, 3486, 3731, 4162], 'artery': [230, 1715, 2415, 2706, 2952, 3487, 3732, 4163, 4415], '(CAD)': [232], 'was': [233, 1252, 1471, 1493], 'published': [234], '2007,': [236], 'identifying': [237, 1815, 1943], 'locus': [239, 896], 'at': [240, 263, 395, 635, 662, 674, 847, 969, 1015, 1271, 1695, 1769, 1798, 1883, 1924], '9p21': [241, 895, 2811], 'conferring': [242], '25%': [244], '30%': [246], 'increase': [247], 'CAD': [252, 301, 325, 337, 433, 508, 645, 702, 762, 812, 831, 841, 851, 888, 900, 921, 949, 963, 1004, 1059, 1089, 1097, 1161, 1250, 1561, 1584, 1613, 1620, 1668, 1735, 1830, 1869, 1878, 1904, 2203, 2237, 2264, 2287, 2328], 'per': [253], 'allele.': [255], 'Now,': [256], '<15': [257], 'years': [258], 'later,': [259], 'common': [260, 604, 2055, 2087, 2749], '>150': [264], 'loci': [265, 296], 'have': [266, 498, 695, 734, 760, 922, 958, 1346, 1621, 1670], 'been': [267, 346, 735, 806, 959, 1672, 2166], 'associated': [268, 506, 897, 1254, 2445], 'with': [269, 307, 324, 387, 419, 507, 533, 569, 747, 754, 766, 886, 899, 908, 1095, 1149, 1206, 1255, 1355, 1372, 1400, 1460, 1475, 1497, 1722, 1852, 2017, 2090, 2273, 2446, 2650, 2753, 2812, 2903, 2944, 3421, 4208], 'CAD.1': [272], 'These': [273, 550, 781, 1032], 'account': [276], 'substantial': [279, 807], 'proportion': [280], 'heritability': [283], 'cardiovascular': [285, 309, 350, 397, 406, 605, 722, 882, 910, 1045, 1104, 1256, 1564, 1705, 1744, 1773, 2170, 2215, 2269, 2451, 2506, 3383, 3419, 3490, 3596, 4075], '(approximately': [287], '35%),': [288], 'although': [290, 634, 1733, 1758, 2016], 'subset': [292], 'these': [294, 357, 529, 939, 1532, 1554, 1600, 1946], 'harbor': [297], 'genes': [298], 'modify': [300], 'based': [303], 'their': [305, 1204, 1234, 1656, 1664], 'traditional': [308, 405, 721, 749, 778, 794, 802, 843, 1024, 1263, 1575, 1743, 2280], 'factors': [311, 796, 845, 1026], '(such': [312], 'as': [313, 461, 463, 652, 764, 2110, 2120, 2243, 2348], 'low-density': [314, 866, 1424, 1596], 'lipoprotein': [315, 867, 1425, 1597], 'cholesterol': [316, 775, 868, 2447, 2502], 'blood': [318, 2501], 'pressure),': [319], 'mechanism': [321], 'unknown': [327], 'majority': [330], 'loci.Since': [332], 'early': [334], 'days': [335], 'GWAS,': [338, 1162], 'use': [340, 708, 876, 1845, 1973], 'has': [345, 536, 805, 904, 2165], 'proposed': [347], 'improve': [349, 403, 738], 'iterations': [355], 'were': [359, 392, 1099, 1216, 1275, 2009], 'simplistically': [360], 'calculated': [361, 555, 618], 'summing': [363], 'number': [365, 1703], 'alleles': [368], 'handful': [371], 'CAD-associated': [373], 'individual': [376, 664, 748, 2822], 'carried,': [377], 'equally,': [379], 'regardless': [380], 'underlying': [383, 577], 'strength': [384, 566], 'CAD.2': [388], 'Although': [389, 1836], 'initial': [390], 'efforts': [391], 'modestly': [393], 'successful': [394], 'predicting': [396, 2267, 4169], 'events,': [398, 1257, 1701, 1774, 2562], 'they': [399, 1539, 2126, 2301, 4166], 'did': [400, 1778], 'not': [401, 657, 670, 1779, 2368], 'substantially': [402], 'factors.': [408, 1265], 'At': [409], 'time,': [411], 'negligible': [413], 'improvements': [414, 1914], 'predictive': [416, 799, 1661, 1724], 'capabilities': [417], 'coupled': [418], 'high': [421, 675, 698, 1249, 1272, 1477, 1480, 1515, 1925, 2286, 2945], 'cost': [422], 'genotyping': [424, 2029], 'made': [425], 'clinical': [426, 693, 817, 1056, 1457, 1481, 1580, 1609, 1859, 2103, 2146, 2155, 2233, 2323, 2565, 2772, 2957, 3057, 3387, 4079, 4174], 'implementation': [427, 2156, 2200, 2221, 2326], 'impractical.Over': [434], 'last': [436], 'decade,': [437], 'growth': [439], 'development': [441], 'large': [443, 464, 530, 1158], 'disease-based': [444], 'consortia': [445], '(eg,': [446, 469, 483, 1693, 2114], 'CARDIoGRAMplusC4D': [447], '[Coronary': [448], 'Replication': [452], 'Meta-Analysis': [454], 'plus': [455], 'Genetics])': [460], 'well': [462], 'disease-agnostic': [465], 'biobanks,': [466], 'both': [467, 713, 1238, 1435, 1506, 1916], 'population': [468, 637], 'deCODE': [470], 'Genetics,': [471, 3041], 'UK': [472, 2694, 4331], 'Biobank,': [473, 478], 'Biobank': [474, 2695, 4332], 'Japan,': [475], 'China': [476], 'Kadoorie': [477], 'Estonian': [479], 'Biobank)': [480], 'medical': [482, 2191], 'VA': [484], 'Million': [485], 'Veteran': [486], 'Program,': [487], 'Vanderbilt': [488], 'BioVu,': [489], 'Geisinger': [490], 'MyCode,': [491], 'Mount': [492, 4296], 'Sinai': [493], 'BioMe,': [494], 'Penn': [495], 'Biobank),': [497], 'enabled': [499], 'brisk': [501], 'discovery': [502], 'other': [510, 777, 833, 2091, 2190], 'complex': [511, 2056, 2413], 'diseases': [512, 2750], 'allowing': [514], 'aggregation': [517], 'hundreds': [519], 'thousands': [521, 557], 'cases': [523], 'controls.': [525], 'availability': [527], 'datasets,': [531], 'along': [532], 'computational': [534], 'advances,': [535], 'allowed': [537], 'easier': [540], 'derivation,': [541], 'calculation,': [542], 'validation': [544], 'polygenic': [546, 1429, 1630, 1802, 1900, 2746, 2775, 2947, 3422, 3483], '(PRS).': [549], 'PRS': [551, 733, 757, 786, 813, 852, 950, 1005, 1041, 1060, 1090, 1251, 1365, 1393, 1562, 1585, 1614, 1665, 1669, 1721, 1736, 1831, 1870, 1941, 1956, 1987, 2084, 2204, 2238, 2265, 2288, 2329], 'now': [553], 'millions': [559, 2005], 'variants,': [562, 1201, 2007], 'variant-level': [565], 'disease,': [570, 932, 1679, 1716], 'integrate': [573], 'information': [574, 2042], 'about': [575], 'relationships': [579], 'accounting': [583, 2278], 'linkage-disequilibrium.Because': [585], 'accumulated': [589], 'continuously': [590], 'over': [591, 603, 647, 1452], 'entire': [593], 'lifespan,': [594], 'may': [598, 703, 727, 787, 1719, 1811, 1948, 2040, 2290, 2954], 'offer': [599], 'potential': [601, 1055, 1844], 'advantage': [602], 'prediction': [607, 631, 740, 839, 2703, 3061], 'tools': [608, 668], 'like': [609, 720], 'Pooled': [611], 'Cohort': [612, 4327], 'Equation,3': [613], 'which': [614, 2008], 'only': [616], 'beginning': [619], 'adulthood.': [621], 'Age': [622], 'dominant': [625], 'factor': [627], 'many': [629, 2054], 'tools,': [632, 2137], 'level': [638], 'age': [639, 1694], 'excellent': [642], 'marker': [643], 'finite': [649], 'time': [650, 1454, 1698], 'such': [651], '10': [653], 'years,': [654], 'it': [655], 'does': [656], 'sufficiently': [658], 'capture': [659, 788, 1739], 'lifetime': [660], 'level.': [665], 'Traditional': [666], 'will': [669, 2138, 2149, 2239], 'identify': [671, 2751], 'young': [672], 'patients': [673, 1094, 1875, 2272, 2289, 2902], 'CAD,': [679, 1207, 1572, 1810, 1854, 2275], 'potentially': [680], 'missing': [681, 2979], 'opportunities': [682, 3029], 'aggressive': [684], 'primordial': [685], 'primary': [687, 714, 825, 1728, 2573, 2664, 2713], 'prevention.': [688], 'Post': [689], 'hoc': [690], 'analyses': [691, 1084, 1545, 1997], 'trials': [694, 990, 1106, 1891], 'demonstrated': [696, 1928], 'mitigated': [705], 'statin': [707, 861, 2568, 2660], 'healthy': [710, 2610], 'lifestyle': [711], 'secondary': [716, 942, 956, 977, 1050, 1730, 2575], 'prevention,4–6': [717], 'suggesting': [718, 1053, 2309], 'that,': [719], 'factors,': [724, 751, 1577, 1746, 2093, 2282], 'modifiable.': [729], 'Studies': [730], 'leveraging': [731], 'newer': [732, 785], 'able': [736, 2011], 'incident': [742, 931, 3417], 'prevalent': [744, 929], 'compared': [746, 1459], 'individuals': [753, 765, 864, 885, 968, 1007, 1014, 1243, 1270, 1336, 1353, 1440, 1474, 1496, 1625, 1651, 1768, 1797, 1851, 1882, 1923, 2752], 'highest': [756], 'appear': [758, 1780], 'similar': [761], 'familial': [767, 2177], 'hypercholesterolemia,': [768, 2178], 'despite': [769], 'having': [770], 'relatively': [771], 'normal': [772], 'levels': [773, 869, 1766], 'factors.7,8': [780], 'findings': [782, 1533], 'suggest': [783, 1508, 1936, 2284], 'residual': [789, 1740], 'left': [791], 'unaccounted': [792], 'add': [798, 2302], 'value': [800, 1662, 2262], 'beyond': [801, 842, 1742], 'factors.There': [804], 'discussion': [808], 'whether': [810, 1629, 1687, 1867, 2125], 'suitable': [815], 'application,': [818], 'primarily': [819, 1140, 1970], 'focused': [820, 924, 1139, 1193, 1623, 1983, 2079], 'application': [823, 1057, 1581, 1610], 'prevention': [826, 943, 957, 1051, 1731, 2576, 2665, 3385, 4077], 'persons': [828], 'without': [829, 1546, 1876], 'pre-existing': [830, 1096, 1571, 1809, 1853, 1877, 2274], 'or': [832, 992, 1345, 1499, 1707, 1885, 2119, 2130, 2374], 'atherosclerotic': [834, 2505, 2904, 3418], 'vascular': [835, 1377, 1402], 'diseases.9': [836], 'By': [837, 3009], 'enhancing': [838], 'earlier': [848], 'ages,': [849], 'could,': [853], 'example,': [855, 1757], 'influence': [856], 'decision': [858, 2147, 2234], 'start': [860], 'therapy': [862, 2661, 2900], 'whose': [865], 'are': [870, 1540, 1864, 2107, 2131, 2367, 4165], 'borderline': [873, 1884], 'range.': [874], 'genetics': [878], 'predict': [880, 1043], 'recurrent': [881, 909, 973, 1044, 1069, 1700, 2268], 'events': [883, 911, 974, 1046, 1565, 2270], 'existing': [887], 'less': [890, 1341], 'clear.': [891], 'Indeed,': [892, 2058], 'well-known': [894], 'strongly': [898, 1253], 'no': [905, 2360], 'clear': [906, 2258], 'setting': [914, 954, 1569, 1588, 1807, 1863], 'established': [916], 'CAD.10': [917], 'Large': [918], 'traditionally': [923], 'combination': [927], 'applicability': [934], 'unclear.': [945, 1755], 'A': [946, 961, 1002, 3668], 'few': [947], 'small': [948], 'performed.': [960], '27-variant': [962], 'score': [966, 2647], 'elevated': [970], 'analysis': [978, 1116, 1168, 1657, 2571], 'CARE': [981], '(Cholesterol': [982], 'Recurrent': [984], 'Events)': [985], 'PROVE': [987], 'IT-TIMI': [988], '22': [989], '(Pravastatin': [991], 'Atorvastatin': [993], 'Evaluation': [994], 'Infection': [996], 'Therapy–Thrombolysis': [997], 'Myocardial': [999], 'Infarction': [1000], '22).4,11': [1001], 'who': [1008, 1098, 1441], 'underwent': [1009], 'cardiac': [1010, 1380, 1405, 2864], 'catheterization': [1011], 'successfully': [1012], 'increased': [1016], 'all-cause': [1019, 2861], 'mortality': [1020, 2862], 'after': [1021, 1259, 2277, 2863], 'adjustment': [1022], 'extent': [1028], 'angiographic': [1030], 'CAD.11': [1031], 'results': [1033, 1235, 1541, 2231, 2911], 'gave': [1034], 'promise': [1035], 'concept': [1038], 'could': [1042, 1589, 1871], 'even': [1047, 1258, 1566, 2276], 'setting,': [1052], 'guiding': [1062, 4173], 'intensity': [1064, 1594], 'preventive': [1066], 'therapies': [1067], 'against': [1068], 'events.In': [1070], 'this': [1071, 1469, 1491, 1587, 1750, 1775, 1862, 2365], 'issue': [1072], 'Circulation,': [1074], 'Marston': [1075, 1134, 1292, 1466, 1967, 2874], 'et': [1076, 1080, 1135, 1189, 1293, 1297, 1299, 1301, 1467, 1489, 1648, 1760, 1968, 1981, 2442, 2481, 2555, 2603, 2643, 2692, 2743, 2806, 2852, 2894, 2941, 4359, 4387], 'al12': [1077], 'Damask': [1079, 1188, 1296, 1488, 1647, 1759, 1980, 2921], 'al13': [1081], 'present': [1082], '2': [1083], 'investigating': [1085], 'role': [1087, 1939], 'stratification': [1092, 1222, 1313, 1632, 1827, 1849, 1902, 2160, 2182, 2316, 2859], 'enrolled': [1100], 'pivotal': [1103], 'outcome': [1105], 'PCSK9': [1109, 1126, 1286, 1448, 1524, 1911, 2297], 'inhibitors': [1110], 'alirocumab': [1111, 2960], 'evolocumab.': [1113], 'In': [1114, 1166, 1266, 1462, 1907], 'FOURIER': [1119, 2914], 'study': [1120, 1173, 1227, 1464, 1486, 1965, 2320, 2820], '(Further': [1121], 'Outcomes': [1123, 1177], 'Research': [1124, 2070], 'Inhibition': [1127], 'Subjects': [1129], 'Elevated': [1131], 'Risk)': [1132], 'al,': [1136, 1190, 1468], 'authors': [1138, 1192, 1433, 1504, 1931], '27–single': [1143, 1976], 'nucleotide': [1144, 1977, 2026], 'polymorphism': [1145, 1978], 'score,': [1148, 1979], 'each': [1150, 1226], 'variant': [1151], 'effect': [1155, 1752, 2022], 'meta-analysis': [1159], 'then': [1164], 'summed.': [1165], '(Evaluation': [1174], 'After': [1178], 'Acute': [1180, 3683], 'Syndrome': [1182], 'During': [1183], 'Alirocumab)': [1186], 'PRS,': [1197, 1428], 'including': [1198, 1804, 2002, 2172], '>6': [1199, 1989], 'million': [1200, 1990], 'adjusted': [1208], 'relationship': [1212], 'variants.': [1214, 1992], 'There': [1215], 'differences': [1217], 'schemes': [1223], 'employed': [1224], '(Table),': [1228], 'making': [1229], 'direct': [1231, 2032], 'comparison': [1232], 'challenging.': [1236], 'However,': [1237, 1551, 2199], 'found': [1240, 1276, 1660], 'among': [1242, 1850, 1922], 'placebo': [1246, 1369], 'arms,': [1247, 1269], 'adjusting': [1260], 'baseline': [1262], 'treatment': [1268, 1395, 1520, 1786, 2197, 2499, 2961], 'derive': [1278, 1444], 'greatest': [1280], 'absolute': [1281, 1919], 'relative': [1283, 1917, 2657], 'benefit': [1284, 1396, 1446, 1521, 1787, 2295, 2566, 2658, 2897, 2958], 'inhibitors.Table.': [1287], 'Comparison': [1288], 'Factors': [1290], 'Between': [1291, 3627], 'al': [1294, 1490, 1649, 1761, 1969, 1982], 'alMarston': [1298], 'al12Damask': [1300], 'al13Polygenic': [1302], 'score27': [1304], '(weighted-sum)≤6': [1306], '579': [1307], '025': [1308], '(LDpred': [1310], 'algorithm)Genetic': [1311], 'strategyHigh': [1314], 'PRS:': [1315, 1319, 1323, 1326, 1330], 'Quintile': [1316, 1324], '5': [1317], 'Intermediate': [1318], 'Quintiles': [1320], '2–4': [1321], 'Low': [1322, 1329], '1High': [1325], '>90th': [1327], 'percentile': [1328], '≤90th': [1331], 'percentileBaseline': [1332], 'characteristics': [1333], 'PRSHigh-risk': [1335], 'younger,': [1337, 1354], 'more': [1338, 1690], 'likely': [1339, 1342, 2293], 'female,': [1340], 'smoke': [1344], 'diabetes': [1347], 'mellitus,': [1348], 'higher': [1349, 1356, 1764, 1770, 2651], 'LDL-C,': [1350, 1357, 1423], 'lower': [1351], 'triglyceridesHigh-risk': [1352], 'non-HDL,': [1358], 'apolipoprotein': [1359], 'B,': [1360, 2439, 3123, 3164, 3216, 3254, 3270, 3334, 3448, 3450, 3470, 3537, 3661, 3815, 3856, 3908, 3946, 3962, 4026, 4260], 'lipoprotein(a)Ancestry>99%': [1361], 'European78%': [1362], 'EuropeanAssociation': [1363], 'group': [1370], '(compared': [1371, 1399], 'low': [1373, 1498, 2117], 'PRS)PRSMajor': [1374], 'eventsMajor': [1376], 'eventsPRSMajor': [1378, 1403], 'adverse': [1379, 1404, 2024], 'eventsHighHR': [1381, 1406], '1.37': [1382], '(1.10–1.71)HR': [1383], '1.65': [1384], '(1.3–2.1)HighHR': [1385], '1.59': [1386], '(1.28–1.96)IntermediateHR': [1387], '1.14': [1388], '(0.94–1.38)HR': [1389], '1.23': [1390], '(0.99–1.52)Association': [1391], 'PCSK9i': [1398], 'placebo)PRSMajor': [1401], '0.69': [1407], '(0.55–.86)HighHR': [1408], '0.61': [1409], '(0.45–0.84)IntermediateHR': [1410], '0.91': [1411], '(0.79–1.03)LowHR': [1412], '0.87': [1413], '(0.77–0.97)LowHR': [1414], '0.92': [1415], '(0.72–1.18)HDL': [1416], 'indicates': [1417], 'high-density': [1418], 'lipoprotein;': [1419], 'HR,': [1420], 'hazard': [1421], 'ratio;': [1422], 'cholesterol;': [1426], 'score.Similarly,': [1431], 'articles': [1436, 1507], 'subgroups': [1438, 1944], 'appeared': [1442], 'little': [1445], 'inhibition': [1449], '(at': [1450], 'least': [1451], 'trials)': [1458], 'placebo.': [1461], 'finding': [1470, 1492], 'evident': [1472, 1494], 'neither': [1476], 'nor': [1479], 'risk,': [1482, 1803, 2558, 2606], 'whereas': [1483], 'intermediate': [1500, 1886], 'risk.': [1502], 'possibility': [1510], 'interaction': [1513], 'derived': [1522], 'inhibitors.': [1525], 'It': [1526], 'important': [1528, 1603], 'note': [1530], 'should': [1534], 'interpreted': [1536], 'cautiously': [1537], 'because': [1538], 'post': [1543], 'hoc/subgroup': [1544], 'correction': [1547], 'multiple': [1549, 2086], 'testing.': [1550], 'taken': [1552], 'together,': [1553], 'provide': [1556, 1840, 2041, 2257], 'strong': [1557], 'evidence': [1558, 1841, 2259, 2308], 'predicts': [1563, 2860], 'independent': [1573], 'titrate': [1593], 'cholesterol–lowering': [1598], 'therapy.Despite': [1599], 'encouraging': [1601], 'findings,': [1602], 'caveats': [1604], 'considerations': [1606], 'regarding': [1607], 'remain.': [1615], 'First,': [1616], 'largely': [1622], 'European': [1627, 3389, 4081], 'ancestry14;': [1628], 'further': [1635, 1681], 'optimized': [1636], 'diverse': [1638], 'populations': [1639, 1823], 'topic': [1642], 'current': [1644, 1838, 1934, 2253], 'intense': [1645], 'investigation.': [1646], 'included': [1650], 'non-European': [1653], 'ancestry': [1654], 'qualitatively': [1659], 'across': [1666], 'ancestries.Second,': [1667], 'typically': [1671], 'using': [1674, 1828, 1998, 2906], 'mixed': [1677], 'incident/prevalent': [1678], 'investigation': [1682], 'warranted': [1684], 'determine': [1686], 'nuanced': [1691], 'phenotypes': [1692], 'event,': [1697], 'total': [1702], 'events)': [1706], 'combined': [1708], 'macrovascular': [1711], '(CAD,': [1713], 'peripheral': [1714], 'ischemic': [1717], 'stroke)': [1718], 'enable': [1720], 'improved': [1723], 'capacity': [1725], 'settings.Third,': [1732], 'appears': [1737], 'mechanisms': [1748], 'behind': [1749], 'modification': [1753], 'remain': [1754, 1832], 'For': [1756], 'genetically': [1763], 'lipoprotein(a)': [1765], 'difference': [1776], 'alone': [1777], 'explain': [1782], 'variation': [1784, 2018], 'high-': [1790], 'low-genetic-risk': [1792], 'groups.': [1793], 'Future': [1794], 'extremes': [1800], 'useful': [1813, 3056, 4167], 'pathways': [1816], 'leading': [1817], 'novel': [1819], 'treatments.Fourth,': [1820], 'target': [1822], 'defined.': [1835, 1962], 'additional': [1855, 1999], 'utility': [1860, 2324, 2773], 'needed.': [1865], 'Determining': [1866], 'applied': [1873, 2167], 'help': [1880], 'reclassify': [1881], 'also': [1888], 'requires': [1889], 'larger': [1890, 2134], 'demonstrate': [1893], 'clinically': [1894, 2109, 2186, 2310], 'meaningful': [1895], 'benefit.Fifth,': [1896], 'cost-effectiveness': [1898], 'remains': [1905, 1959], 'unstudied.': [1906], 'case': [1909], 'inhibitors,': [1912], 'reduction': [1921], 'possible': [1938], 'where': [1945], 'medications': [1947], 'most': [1950, 1954, 2292], 'cost-effective.': [1951], 'Finally,': [1952], 'effective': [1955], 'screening': [1957, 2195], 'technology': [1958], 'Whereas': [1963], 'studied': [1971], 'comprising': [1988], 'Both': [1993], 'groups': [1994], 'performed': [1995], 'sensitivity': [1996], 'tens': [2003], 'broadly': [2010], 'stratify': [2014], 'individuals,': [2015], 'estimated': [2021], 'outcomes.Single': [2025], 'polymorphism–based': [2027], 'available': [2031], 'consumers': [2034], '$50': [2036], '$100': [2038], 'simultaneously': [2045], 'assessing': [2049], 'diseases.8': [2057], 'next': [2060], 'iteration': [2061], 'NHGRI': [2064], 'eMERGE': [2065], 'consortium': [2066], '(National': [2067], 'Human': [2068, 3040], 'Genome': [2069], 'Institute': [2071], 'Electronic': [2072, 2990], 'Medical': [2073, 2991], 'Records': [2074, 2992], 'Genomics': [2076, 2994, 4274], 'Network)': [2077], 'generation': [2082], 'diseases,': [2088, 2171], 'integration': [2089], 'return': [2095], 'genomic': [2098], 'assessment': [2100], 'context.15': [2104], 'Whether': [2105], 'implemented': [2108], 'stratified': [2112], 'variable': [2113], 'high,': [2115], 'intermediate,': [2116], 'risk)': [2118], 'continuous': [2122], 'variable,': [2123], 'function': [2127], 'isolation': [2129], 'incorporated': [2132], 'calculation': [2136], 'need': [2139, 2150], 'determined.': [2142], 'Pathways,': [2143], 'guidelines,': [2144], 'support': [2148, 2235], 'developed': [2153], 'CAD.': [2162, 2318], 'testing': [2164, 2249], 'Mendelian': [2169, 2214], 'inherited': [2173], 'cardiomyopathies,': [2174], 'arrhythmias,': [2175], 'currently': [2184], 'within': [2187], 'oncology': [2188], 'subspecialties': [2192], 'alter': [2194], 'decisions.': [2198], 'fundamentally': [2206], 'different': [2207], 'molecular': [2210], 'diagnosis': [2211], 'condition,': [2216], 'route': [2219], 'clinical-grade': [2223], 'testing,': [2225], 'appropriate': [2226], 'counseling,': [2227], 'incorporation': [2229], 'challenging,': [2241], 'particularly': [2242], 'market': [2245], 'consumer': [2247], 'grows.In': [2250], 'summary,': [2251], 'Circulation': [2256], 'inhibition.': [2298], 'As': [2299], 'such,': [2300], 'growing': [2305], 'body': [2306], 'impactful': [2311], 'roles': [2312], 'Ongoing': [2319], 'warranted.DisclosuresDr': [2331], 'Scientific': [2335, 2350], 'Advisory': [2336], 'Boards': [2337], 'Alnylam': [2339], 'Pharmaceuticals,': [2340], 'Novartis,': [2341], 'Pfizer,': [2342], 'Verve': [2344], 'Therapeutics': [2345], 'serves': [2347], 'Chief': [2349], 'Advisor': [2351], 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[3092, 3644, 3689], 'Advances': [3095], 'Technology,': [3098], '10.1016/B978-0-12-816861-5.00004-6,': [3099], '(603-624),': [3100], '.': [3101, 3722], 'Visseren': [3102, 3513, 3794], 'Mach': [3104, 3515, 3796], 'Smulders': [3106, 3317, 3518, 3798, 4009], 'Carballo': [3108, 3319, 3520, 3800, 4011], 'Koskinas': [3110, 3321, 3523, 3802, 4013], 'Bäck': [3112, 3180, 3323, 3525, 3804, 3872, 4015], 'Benetos': [3114, 3325, 3527, 3806, 4017], 'Biffi': [3116, 3327, 3529, 3808, 4019], 'Boavida': [3118, 3329, 3532, 3810, 4021], 'Capodanno': [3120, 3331, 3534, 3812, 4023], 'Cosyns': [3122, 3333, 3536, 3814, 4025], 'Crawford': [3124, 3335, 3538, 3816, 4027], 'Davos': [3126, 3337, 3541, 3818, 4029], 'Desormais': [3128, 3339, 3543, 3820, 4031], 'Di': [3130, 3341, 3545, 3822, 4033], 'Angelantonio': [3131, 3342, 3546, 3823, 4034], 'Franco': [3133, 3344, 3549, 3825, 4036], 'Halvorsen': [3135, 3347, 3551, 3827, 4039], 'Hobbs': [3137, 3350, 3554, 3829, 4042], 'Hollander': [3139, 3352, 3556, 3831, 4044], 'Jankowska': [3141, 3354, 3559, 3833, 4046], 'Michal': [3143, 3356, 3561, 3835, 4048], 'Sacco': [3145, 3358, 3563, 3837, 4050], 'Sattar': [3147, 3360, 3565, 3839, 4052], 'N,': [3148, 3195, 3284, 3361, 3452, 3566, 3655, 3840, 3887, 3976, 4053], 'Tokgozoglu': [3149, 3362, 3567, 3841, 4054], 'Tonstad': [3151, 3364, 3569, 3843, 4056], 'Tsioufis': [3153, 3366, 3572, 3845, 4058], 'van': [3155, 3158, 3370, 3574, 3578, 3847, 3850, 4062, 4301], 'Dis': [3156, 3368, 3575, 3848, 4060], 'Gelder': [3159, 3371, 3579, 3851, 4063], 'Wanner': [3161, 3373, 3581, 3853, 4065], 'De': [3165, 3196, 3199, 3857, 3888, 3891], 'Backer': [3166, 3197, 3858, 3889], 'Regitz-Zagrosek': [3168, 3860], 'Aamodt': [3170, 3862], 'Abdelhamid': [3172, 3864], 'Aboyans': [3174, 3866], 'Albus': [3176, 3868], 'Asteggiano': [3178, 3870], 'Borger': [3182, 3874], 'Brotons': [3184, 3876], 'Čelutkienė': [3186, 3878], 'Cifkova': [3188, 3880], 'Cikes': [3190, 3882], 'Cosentino': [3192, 3884], 'Dagres': [3194, 3886], 'Bacquer': [3200, 3892], 'Delgado': [3202, 3894], 'Den': [3204, 3896], 'Ruijter': [3205, 3897], 'Dendale': [3207, 3899], 'Drexel': [3209, 3901], 'Falk': [3211, 3903], 'Fauchier': [3213, 3905], 'Ference': [3215, 3907], 'Ferrières': [3217, 3909], 'Ferrini': [3219, 3911], 'Fisher': [3221, 3913], 'Fliser': [3223, 3915], 'Fras': [3225, 3917], 'Gaita': [3227, 3919], 'Giampaoli': [3229, 3921], 'Gielen': [3231, 3923], 'Graham': [3233, 3925], 'Jennings': [3235, 3927], 'Jorgensen': [3237, 3929], 'Kautzky-Willer': [3239, 3931], 'Kavousi': [3241, 3933], 'Koenig': [3243, 3935], 'W,': [3244, 3310, 3619, 3936, 4002], 'Konradi': [3245, 3937], 'Kotecha': [3247, 3939], 'Landmesser': [3249, 3941], 'Lettino': [3251, 3943], 'Lewis': [3253, 3945], 'Linhart': [3255, 3947], 'Løchen': [3257, 3949], 'Makrilakis': [3259, 3951], 'Mancia': [3261, 3953], 'Marques-Vidal': [3263, 3955], 'McEvoy': [3265, 3957], 'McGreavy': [3267, 3959], 'Merkely': [3269, 3961], 'Neubeck': [3271, 3963], 'Nielsen': [3273, 3965], 'Perk': [3275, 3967], 'Petersen': [3277, 3969], 'Petronio': [3279, 3971], 'Piepoli': [3281, 3973], 'Pogosova': [3283, 3975], 'Prescott': [3285, 3977], 'Ray': [3287, 3979], 'Reiner': [3289, 3981], 'Richter': [3291, 3983], 'Rydén': [3293, 3985], 'Shlyakhto': [3295, 3987], 'Sitges': [3297, 3989], 'Sousa-Uva': [3299, 3991], 'Sudano': [3301, 3993], 'Tiberi': [3303, 3995], 'Touyz': [3305, 3997], 'Ungar': [3307, 3999], 'Verschuren': [3309, 4001], 'Wiklund': [3311, 4003], 'Zamorano': [3315, 4007], 'Duran': [3345, 4037], 'Richard': [3349, 3553, 4041], 'B': [3377, 3585, 4069, 4306], '2021': [3379, 3589, 4071], 'ESC': [3380, 3588, 4072], 'Guidelines': [3381, 4073], 'practice,': [3388, 4080], 'Journal': [3390, 3738, 4106, 4135, 4213, 4334], 'Preventive': [3392, 4325], 'Cardiology,': [3393, 4141], '10.1093/eurjpc/zwab154,': [3394], '29:1,': [3395], '(5-115),': [3396], '19-Feb-2022.': [3400], 'Song': [3401], 'Koh': [3403], 'Rhee': [3405], 'Kang': [3409], 'S': [3410, 3413, 4303], 'Lee': [3412, 3757, 3759], 'Prediction': [3415, 3681, 4199], 'metabolic': [3425], 'disease:': [3426, 4164], 'Analysis': [3427], '3': [3429], 'prospective': [3430], 'cohort': [3431], 'Korea,': [3434], 'Atherosclerosis,': [3435], '10.1016/j.atherosclerosis.2022.03.021,': [3436], '348,': [3437], '(16-24),': [3438], '1-May-2022.': [3442, 3611], 'Zhang': [3443], 'Hill': [3445], 'Guo': [3447], 'Wu': [3449], 'Alliey-Rodriguez': [3451], 'Eum': [3453], 'Lizano': [3455], 'Ivleva': [3457], 'Keefe': [3461], 'Keedy': [3463], 'Tamminga': [3465], 'Pearlson': [3467], 'Clementz': [3469], 'Keshavan': [3471], 'Gershon': [3473], 'Sweeney': [3475], 'Bishop': [3478], 'Impact': [3481, 3674], 'medication': [3491], 'cognitive': [3494], 'impairment': [3495], 'psychotic': [3497], 'disorders,': [3498], 'Progress': [3499], 'Neuro-Psychopharmacology': [3501], 'Biological': [3503], 'Psychiatry,': [3504], '10.1016/j.pnpbp.2021.110464,': [3505], '113,': [3506], '(110464),': [3507], '1-Mar-2022.': [3511], 'L.J.': [3512], 'C.': [3522, 3577], 'Manuel': [3531], 'H.': [3540, 3548], 'A.': [3558, 4357], 'P.': [3571], 'Guía': [3587], 'sobre': [3590], 'la': [3591, 3594, 3598], 'prevención': [3592], 'de': [3593, 3603, 4298], 'enfermedad': [3595], 'en': [3597], 'práctica': [3599], 'clínica,': [3600], 'Revista': [3601], 'Española': [3602], 'Cardiología,': [3604], '10.1016/j.recesp.2021.10.016,': [3605], '75:5,': [3606], '(429.e1-429.e104),': [3607], 'Ye': [3612], 'X,': [3615, 4223], 'Han': [3616], 'Jiang': [3618], 'Zhao': [3623], 'H': [3624, 3727, 4124, 4196], 'Interactions': [3626], 'Enhanced': [3628], 'Lifestyle': [3633], 'Disease,': [3636, 4134, 4319], 'Diabetes,': [3637, 4320], 'Lipid': [3639], 'Levels,': [3640], 'Circulation:': [3641, 3686], '14:1,': [3646], '1-Feb-2021.Lee': [3650], 'Kiiskinen': [3652], 'Mars': [3654], 'Jukarainen': [3656], 'Ingelsson': [3658], 'Neale': [3660], 'Ripatti': [3662], 'Ganna': [3667], 'Conditions': [3671], 'Their': [3673], 'Utility': [3676], 'Syndrome,': [3685], '14:4,': [3691], '1-Aug-2021.': [3695], 'Chang': [3696, 3755], 'Y': [3697], 'K': [3700, 4095], 'Therapeutic': [3702], 'perspectives': [3703], 'extracellular': [3705, 3708], 'vesicles': [3706], 'microRNAs': [3709], 'Cellular': [3712], 'Mechanotransduction': [3713], 'Mechanisms': [3714], 'Fibrotic': [3718], 'Diseases,': [3719], '10.1016/bs.ctm.2021.08.005,': [3720], '(255-277),': [3721], 'Z': [3724], 'Schunkert': [3726, 4195], 'post‐GWAS': [3736], 'era,': [3737], 'Internal': [3740], '10.1111/joim.13362,': [3742], '290:5,': [3743], '(980-992),': [3744], '1-Nov-2021.': [3748], 'Liu': [3749, 3772], 'Huang': [3751], 'Hsu': [3753], 'Li': [3763, 4220], 'Chao': [3765], 'Su': [3767], 'Shen': [3769], 'model': [3777], 'in-stent': [3779], 'restenosis': [3780], 'second-and': [3782], 'third-generation': [3783], 'drug-eluting': [3784], 'stents,': [3785], 'iScience,': [3786], '10.1016/j.isci.2021.103082,': [3787], '24:9,': [3788], '(103082),': [3789], '1-Sep-2021.': [3793], 'Journal,': [4083], '10.1093/eurheartj/ehab484,': [4084], '42:34,': [4085], '(3227-3337),': [4086], '7-Sep-2021.': [4090], 'Lin': [4091, 4123], 'Susztak': [4094], '(2020)': [4096, 4125, 4154], 'Complexities': [4097], 'Understanding': [4099], 'Function': [4100], 'CKD-Associated': [4102], 'DNA': [4103], 'Variants,': [4104], 'Society': [4110], 'Nephrology,': [4112], '10.2215/CJN.15771219,': [4113], '15:7,': [4114], '(1028-1040),': [4115], '1-Jul-2020.': [4119], 'Rotter': [4120], 'An': [4126, 4155], 'Outbreak': [4127], '10.1016/j.jacc.2020.04.054,': [4142], '75:22,': [4143], '(2781-2784),': [4144], '1-Jun-2020.': [4148], 'Lieb': [4149], 'Vasan': [4152], 'R': [4153], 'update': [4156], 'decisions?,': [4175], 'Expert': [4176], 'Review': [4177], 'Therapy,': [4180], '10.1080/14779072.2020.1797489,': [4181], '18:8,': [4182], '(443-447),': [4183], '2-Aug-2020.': [4187], 'Westerlund': [4188], 'Hawe': [4190], 'Heinig': [4192], 'Events': [4202], 'Exploration': [4204], 'Molecular': [4206, 4215], 'Data': [4207], 'Explainable': [4209], 'Artificial': [4210], 'Intelligence,': [4211], 'International': [4212], 'Sciences,': [4216], '10.3390/ijms221910291,': [4217], '22:19,': [4218], '(10291)': [4219], 'Q,': [4221], 'Lv': [4222], 'Jin': [4224], 'Liao': [4226], 'Gao': [4228], 'L': [4229], 'Xu': [4231], 'Associations': [4234], 'Score': [4238], 'Late-Onset': [4240], "Alzheimer's": [4241], 'Biomarkers,': [4244], 'Frontiers': [4245, 4281], 'Aging': [4247], 'Neuroscience,': [4248], '10.3389/fnagi.2022.849443,': [4249], '14': [4250], 'Zimmermann': [4253], 'Hekman': [4255], 'Lord': [4257], 'Logan': [4259], 'Russenberger': [4261], 'Leighton': [4263], 'E': [4264, 4267], 'Karlsson': [4266], 'Advancing': [4269], 'Selection': [4271], 'Behavioral': [4273], 'Dogs': [4277], 'Through': [4278], 'Collaborative': [4279], 'Science,': [4280, 4284], 'Veterinary': [4283], '10.3389/fvets.2021.662429,': [4285], '8': [4286, 4396], 'Castela': [4287], 'Forte': [4288], 'Folkertsma': [4290], 'Gannamani': [4292], 'Kumaraswamy': [4294], 'Koning': [4299], 'Dam': [4302], 'Wolffenbuttel': [4305], 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