| CPC C12Q 1/6883 (2013.01) [G16B 10/00 (2019.02); G16B 20/20 (2019.02); G16B 40/00 (2019.02); C12Q 2600/106 (2013.01); C12Q 2600/118 (2013.01); C12Q 2600/156 (2013.01)] | 20 Claims |
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1. A method for predicting a subject's risk of diabetes complications and/or response to therapy, the method comprising:
(a) genotyping said subject at a plurality of risk alleles associated with the diabetes complications and their risk factors;
(b) genotyping said subject at a plurality of ancestry-informative markers;
(c) providing a computer programmed with information of a matching cohort of subjects with outcome data over a selected period of interest, the matching cohort of subjects being diagnosed with diabetes or pre-diabetes and being genotyped at said plurality of risk alleles and at said plurality of ancestry-informative markers;
(d) generating a polygenic risk score (PRS) by calculating weighted genetic risk scores (wGRS) weighting the number of risk alleles by the effect size of their associations, adding to said wGRS a geo-ethnic principal component (PC) value determined from the subject's genotype at said ancestry-informative markers, and comparing the PRS of said subject with that constructed using a logistic regression model from said matching cohort of subjects with outcome data collected during the selected period of interest; and
(e) predicting said subject's risk of diabetes complications and/or response to therapy based on said PRS, wherein:
the plurality of risk alleles comprise at least 100 different single nucleotide polymorphisms (SNPs) selected from: rs10923931, rs2779116, rs340874, rs7578597, rs243021, rs7593730, rs552976, rs7578326, rs1801282, rs4607103, rs11708067, rs1470579, rs10010131, rs7754840, rs1800562, rs9472138, rs2191349, rs864745, rs1799884, rs4607517, rs972283, rs4737009, rs896854, rs13266634, rs10811661, rs13292136, rs12779790, rs1111875, rs2334499, rs231362, rs2237892, rs5215, rs1552224, rs1387153, rs10830963, rs1153188, rs1531343, rs7961581, rs7957197, rs7998202, rs11634397, rs8042680, rs9939609, rs1046896, rs855791, rs3127553, rs2815752, rs7531118, rs1514175, rs4130548, rs11165623, rs1555543, rs984222, rs1011731, rs633715, rs543874, rs2820292, rs4846567, rs6429082, rs2867125, rs6755502, rs713586, rs887912, rs6545714, rs2890652, rs10195252, rs2176040, rs6784615, rs6795735, rs3849570, rs2325036, rs13078807, rs6440003, rs9816226, rs1516725, rs10938397, rs2112347, rs4836133, rs6861681, rs1294421, rs806794, rs206936, rs16894959, rs6905288, rs987237, rs943005, rs9400239, rs9491696, rs2489623, rs1055144, rs10968576, rs6163, rs7903146, rs4929949, rs10840100, rs10767658, rs10767664, rs2293576, rs3817334, rs7121446, rs718314, rs7138803, rs1443512, rs4771122, rs12429545, rs10132280, rs12885454, rs10150332, rs7144011, rs4776970, rs2241423, rs2531992, rs12444979, rs12446632, rs2650492, rs7498665, rs7359397, rs1549293, rs1558902, rs7239883, rs6567160, rs571312, rs29941, rs3810291, rs16996700, rs4823006, rs11579312, rs4072037, rs914615, rs13427836, rs17346504, rs16827742, rs11678190, rs11678190, rs13079877, rs1077216, rs7634770, rs13160548, rs12719264, rs17738155, rs2110904, rs4722909, rs17301329, rs7851726, rs1109861, rs17343073, rs1801239, rs6602163, rs12764441, rs3740393, rs7922045, rs729014, rs10899033, rs649529, rs2303658, rs7145202, rs1728897, rs1528472, rs231227, rs6513791, rs2828785, rs1800615, rs12136063, rs267734, rs3850625, rs2802729, rs807601, rs1260326, rs6546838, rs13538, rs4667594, rs2712184, rs6795744, rs2861422, rs347685, rs9682041, rs10513801, rs17319721, rs228611, rs11959928, rs11959928, rs7759001, rs881858, rs9472135, rs316009, rs3127573, rs3750082, rs848490, rs7805747, rs7805747, rs3758086, rs1731274, rs4744712, rs1044261, rs10994860, rs163160, rs963837, rs4014195, rs10774021, rs10491967, rs7956634, rs1106766, rs653178, rs716877, rs626277, rs476633, rs2453533, rs2467853, rs491567, rs1394125, rs4293393, rs13329952, rs164748, rs11657044, rs8068318, rs12460876, rs11666497, rs6088580, rs17216707, rs4821467, rs17367504, rs17367504, rs848309, rs4360494, rs112557609, rs3889199, rs2932538, rs2289081, rs11690961, rs74181299, rs11689667, rs1250259, rs13082711, rs3774372, rs419076, rs419076, rs871606, rs1458038, rs13107325, rs78049276, rs146853253, rs13139571, rs1566497, rs17059668, rs1173771, rs10057188, rs31864, rs1799945, rs805303, rs185819, rs11154027, rs36083386, rs449789, rs1322639, rs76206723, rs17477177, rs6557876, rs35783704, rs2071518, rs4454254, rs72765298, rs4373814, rs1813353, rs9337951, rs10826995, rs4590817, rs932764, rs11191548, rs7129220, rs381815, rs11442819, rs2289125, rs633185, rs8258, rs11222084, rs10770612, rs73099903, rs7312464, rs17249754, rs139236208, rs3184504, rs3184504, rs10850411, rs12434998, rs9323988, rs1378942, rs56249585, rs7500448, rs7226020, rs62080325, rs17608766, rs12940887, rs57927100, rs7236548, rs2116941, rs2206815, rs1327235, rs6081613, rs6015450, rs6015450, rs73161324, rs12628032, rs12037222, rs4420065, rs4129267, rs2794520, rs12239046, rs1260326, rs6734238, rs511154, rs1800789, rs2522056, rs4705952, rs6901250, rs13233571, rs9987289, rs10745954, rs1183910, rs340029, rs2847281, rs4420638, rs12027135, rs4660293, rs2479409, rs2131925, rs7515577, rs629301, rs1689800, rs2642442, rs4846914, rs514230, rs1367117, rs4299376, rs7570971, rs2972146, rs2290159, rs645040, rs442177, rs6450176, rs9686661, rs12916, rs6882076, rs3757354, rs3177928, rs2814944, rs9488822, rs605066, rs1564348, rs12670798, rs2072183, rs17145738, rs4731702, rs11776767, rs1495741, rs12678919, rs2081687, rs2293889, rs2954029, rs11136341, rs581080, rs1883025, rs9411489, rs10761731, rs2255141, rs2923084, rs10128711, rs3136441, rs174546, rs12280753, rs964184, rs7941030, rs11220462, rs7134375, rs11613352, rs7134594, rs1169288, rs4759375, rs4765127, rs2929282, rs1532085, rs11649653, rs3764261, rs16942887, rs2000999, rs2925979, rs11869286, rs7206971, rs4148008, rs4129767, rs7241918, rs12967135, rs737337, rs10401969, rs2277862, rs2902940, rs6029526, rs6065906, rs181362, rs5756931, rs161802, rs225132, rs11206510, rs17114036, rs9970807, rs56170783, rs7528419, rs646776, rs646776, rs602633, rs12122341, rs11810571, rs6689306, rs12118721, rs13376333, rs1800594, rs10911021, rs35700460, rs17465637, rs17465637, rs67180937, rs585967, rs4299376, rs13407662, rs10176176, rs7568458, rs17678683, rs6725887, rs6725887, rs114123510, rs1250229, rs13003675, rs7623687, rs142695226, rs139016349, rs9818870, rs16851055, rs12493885, rs72627509, rs10857147, rs2634074, rs12646447, rs17042171, rs2200733, rs1906599, rs6843082, rs7678555, rs4593108, rs6841581, rs2306556, rs72689147, rs7692395, rs4975709, rs9369640, rs9349379, rs12526453, rs6909752, rs3130683, rs4472337, rs12205331, rs1544935, rs56015508, rs2916260, rs556621, rs632728, rs783396, rs12202017, rs12190287, rs6922269, rs2048327, rs10455872, rs10455872, rs2315065, rs6941513, rs4721377, rs10486776, rs12669789, rs11984041, rs11984041, rs7798197, rs2107595, rs2107595, rs10230207, rs112370447, rs11556924, rs11556924, rs264, rs2083636, rs2001846, rs2954029, rs6475606, rs1537370, rs4977574, rs4977574, rs2891168, rs10757278, rs1333047, rs1333049, rs514659, rs514659, rs532436, rs1887318, rs2505083, rs1870634, rs501120, rs1746048, rs1746048, rs1004467, rs11191416, rs12413409, rs11196288, rs10840293, rs3993105, rs2019090, rs2839812, rs9326246, rs964184, rs12425791, rs2229357, rs2681472, rs3184504, rs10774625, rs653178, rs2238151, rs10744777, rs17696736, rs2244608, rs11057830, rs4304924, rs16945184, rs11617955, rs55940034, rs1924981, rs12435908, rs1005224, rs963474, rs10139550, rs72743461, rs1994016, rs1994016, rs3825807, rs7164479, rs7165042, rs7173743, rs2083460, rs247616, rs7193343, rs2106261, rs879324, rs7500448, rs4843416, rs113348108, rs2281727, rs9914266, rs4792143, rs12936587, rs9897596, rs35895680, rs4643373, rs7212798, rs8068952, rs6565653, rs1122608, rs1122608, rs8108632, rs56131196, rs28451064, rs9982601, rs9982601, rs2473248, rs4330912, rs72480273, rs61830764, rs7575873, rs1374204, rs2168443, rs11719201, rs10935733, rs900399, rs2724475, rs2131354, rs4432842, rs2946179, rs35261542, rs9379832, rs9368777, rs1187118, rs1415701, rs10872678, rs798489, rs11765649, rs6959887, rs62466330, rs13266210, rs6989280, rs12543725, rs12551019, rs3780573, rs1411424, rs4836833, rs10818797, rs2497304, rs79237883, rs740746, rs2421016, rs10830963, rs11055034, rs2306547, rs1351394, rs7964361, rs7998537, rs34217484, rs1819436, rs7402982, rs1011939, rs113086489, rs72833480, rs10402712, rs6040076, rs28530618, rs6016377, rs2229742, and rs134594;
the plurality of ancestry-informative markers comprise at least 1000 different SNPs; and
the wGRS is determined by the equation
 where Xijk is the allele frequency of ith subject in jth SNP for kth phenotype, and β is the effect size of the phenotype.
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