Polygenic risk scores for predicting disease complications and/or response to therapy

Patent metadata

Field	Value
Publication number	US-12467091-B2
Application number	US-201917252140-A
Country	US
Kind code	B2
Filing date	Jun 14, 2019
Priority date	Jun 15, 2018
Publication date	Nov 11, 2025
Grant date	Nov 11, 2025

Abstract

Methods, processes, and systems for predicting a subject's disease complications and/or response to therapy are described herein. The methods generally comprise genotyping or receiving genotyping information from the subject at a plurality of risk alleles associated with the disease and at a plurality of ancestry-informative markers. The genotyping information is used to generate a polygenic risk score (PRS) by weighting the number of risk alleles by the effect size of their association (weighted genetic risk score or wGRS), combined with a geo-ethnic principal component (PC) determined from the subject's genotype at said ancestry-informative markers. The PRS enables better prediction of the subject's disease complications and/or response to therapy, as compared to a corresponding PRS generated lacking the geo-ethnic principal component. Computer-implemented methods and processes are also described herein.

First claim

The invention claimed is:

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, rs1087

Assignees

• Opti Thera Inc
• Servier Lab
• Val Chum Lp

Inventors

• Hamet Pavel
• Tremblay Johanne

Classifications

• C12Q2600/156

  Polymorphic or mutational markers · CPC title

• C12Q2600/118

  Prognosis of disease development · CPC title

• C12Q2600/106

  Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism · CPC title

• G16B40/00

  ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding · CPC title

• G16B10/00

  ICT specially adapted for evolutionary bioinformatics, e.g. phylogenetic tree construction or analysis · CPC title