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Cochran–Armitage test for trend

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1015: 753: 1176:, and we refer to these as aa, Aa and AA. The distribution of genotype counts can be put in a 2 × 3 contingency table. For example, consider the following data, in which the genotype frequencies vary linearly in the cases and are constant in the controls: 1332:
and the Pearson chi-squared test gives a standardized test statistic of 2. Thus, we obtain a stronger significance level if the weights corresponding to additive (codominant) inheritance are used. Note that for the significance level to give a
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categories of the second variable. For example, doses of a treatment can be ordered as 'low', 'medium', and 'high', and we may suspect that the treatment benefit cannot become smaller as the dose increases. The trend test is often used as a
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than the chi-squared test when the suspected trend is correct, but the ability to detect unsuspected trends is sacrificed. This is an example of a general technique of directing hypothesis tests toward narrow
640: 625: 1570: 1010:{\displaystyle {\rm {Var}}(T)={\frac {R_{1}R_{2}}{N}}\left(\sum _{i=1}^{k}t_{i}^{2}C_{i}(N-C_{i})-2\sum _{i=1}^{k-1}\sum _{j=i+1}^{k}t_{i}t_{j}C_{i}C_{j}\right),} 1156:. The trend test exploits the suspected effect direction to increase power, but this does not affect the sampling distribution of the test statistic under the 1026: 1337:
with the usual probabilistic interpretation, the weights must be specified before examining the data, and only one set of weights may be used.
351: 1346: 1135: = (0,1,2) should be used. These weights are also often used when the frequencies are suspected to change monotonically with 1371: 748:{\displaystyle \operatorname {E} (T)=\operatorname {E} \left(\operatorname {E} (T|R_{1},R_{2})\right)=\operatorname {E} (0)=0.} 1160:. Thus, the suspected trend in effects is not an assumption that must hold in order for the test results to be meaningful. 1287: 25: 537: 29: 41: 33: 21: 1259: 1153: 1131: = (1,1,0) should be used. If we suspect a linear trend in the frequencies, then the weights 1267: 60: 1498: 1463: 1398: 54: 1547: 1406: 1367: 1148: 1108: 75: 1419: 1537: 1529: 1490: 1455: 1390: 1173: 1293:
In the numerical example, the standardized test statistics for various weight vectors are
1283: 1157: 528: 1542: 1517: 631: 342: 1518:"PLINK: a tool set for whole-genome association and population-based linkage analyses" 1564: 1446:
Cochran, WG (1954). "Some methods for strengthening the common chi-squared tests".
1359: 1420:"A derivation for Armitage's trend test for the 2 × 3 genotype table" 1481:
Armitage, P (1955). "Tests for Linear Trends in Proportions and Frequencies".
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In genetics applications, the weights are selected according to the suspected
1088:{\displaystyle {\frac {T}{\sqrt {\mathrm {Var} (T)}}}\sim \mathrm {N} (0,1).} 1551: 1410: 160:
This table can be completed with the marginal totals of the two variables
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The trend test is applied when the data take the form of a 2 × 
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Sasieni, P (1997). "From genotypes to genes: doubling the sample size".
1502: 1467: 1402: 1334: 1266: = (1, 1, 0) is locally optimal. To test whether allele a is 453:{\displaystyle T\equiv \sum _{i=1}^{k}t_{i}(N_{1i}R_{2}-N_{2i}R_{1}),} 1255: 1494: 1459: 1394: 1123: = 2 have similar frequencies (within each row), but that 36:
between a variable with two categories and an ordinal variable with
1533: 1290:, the additive (or codominant) version of the test is often used. 1111:
for detecting particular types of associations. For example, if
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Purcell S, Neale B, Todd-Brown K, et al. (September 2007).
1274: = (0, 1, 1). To test whether alleles a and A are 1107:
can be chosen such that the trend test becomes locally most
1127: = 3 has a different frequency, then the weights 44:
to incorporate a suspected ordering in the effects of the
1029: 771: 643: 540: 354: 1286:, the underlying genetic model is often unknown. In 524:after reweighting the rows to have the same total. 1087: 1009: 747: 620:{\displaystyle \Pr(A=1|B=1)=\cdots =\Pr(A=1|B=k).} 619: 452: 32:when the aim is to assess for the presence of an 582: 541: 1489:(3). International Biometric Society: 375–386. 1454:(4). International Biometric Society: 417–451. 1389:(4). International Biometric Society: 1253–61. 1282: = (0, 1, 2) is locally optimal. For 1139:, even if the trend is not necessarily linear. 8: 1541: 1062: 1036: 1030: 1028: 993: 983: 973: 963: 953: 936: 920: 909: 890: 871: 861: 856: 846: 835: 814: 804: 797: 773: 772: 770: 707: 694: 685: 642: 597: 556: 539: 438: 425: 412: 399: 386: 376: 365: 353: 1571:Statistical tests for contingency tables 1295: 1254:. For example, in order to test whether 1178: 162: 84: 1438: 1168:Suppose that there are three possible 527:The hypothesis of no association (the 504:can be seen as the difference between 1020:and as a large sample approximation, 7: 1347:List of analyses of categorical data 1270:to allele A, the optimal choice is 1115: = 3 and we suspect that 1063: 1043: 1040: 1037: 780: 777: 774: 724: 673: 662: 644: 14: 630:Assuming this holds, then, using 1147:The trend test will have higher 758:The variance can be computed by 472:are weights, and the difference 1288:genome-wide association studies 18:Cochran–Armitage test for trend 1079: 1067: 1053: 1047: 896: 877: 791: 785: 736: 730: 713: 686: 679: 656: 650: 611: 598: 585: 570: 557: 544: 444: 392: 1: 40:categories. It modifies the 1302:Standardized test statistic 1587: 1366:(Second ed.). Wiley. 1262:over allele A, the choice 1364:Categorical Data Analysis 30:categorical data analysis 42:Pearson chi-squared test 1164:Application to genetics 1143:Interpretation and role 531:) can be expressed as: 82: = 3 we have 1089: 1011: 958: 931: 851: 749: 621: 454: 381: 1090: 1012: 932: 905: 831: 750: 622: 455: 361: 1418:statgen.org (2007). 1027: 769: 641: 632:iterated expectation 538: 352: 1252:mode of inheritance 1119: = 1 and 866: 78:. For example, if 61:association studies 1085: 1007: 852: 745: 617: 450: 1522:Am. J. Hum. Genet 1330: 1329: 1248: 1247: 1057: 1056: 824: 287: 286: 158: 157: 76:contingency table 1578: 1556: 1555: 1545: 1513: 1507: 1506: 1478: 1472: 1471: 1443: 1433: 1431: 1429: 1424: 1414: 1377: 1296: 1284:complex diseases 1179: 1094: 1092: 1091: 1086: 1066: 1058: 1046: 1035: 1031: 1016: 1014: 1013: 1008: 1003: 999: 998: 997: 988: 987: 978: 977: 968: 967: 957: 952: 930: 919: 895: 894: 876: 875: 865: 860: 850: 845: 825: 820: 819: 818: 809: 808: 798: 784: 783: 754: 752: 751: 746: 720: 716: 712: 711: 699: 698: 689: 626: 624: 623: 618: 601: 560: 459: 457: 456: 451: 443: 442: 433: 432: 417: 416: 407: 406: 391: 390: 380: 375: 163: 85: 53:-based test for 1586: 1585: 1581: 1580: 1579: 1577: 1576: 1575: 1561: 1560: 1559: 1515: 1514: 1510: 1495:10.2307/3001775 1480: 1479: 1475: 1460:10.2307/3001616 1445: 1444: 1440: 1427: 1425: 1422: 1417: 1395:10.2307/2533494 1380: 1374: 1358: 1355: 1343: 1166: 1158:null hypothesis 1145: 1106: 1025: 1024: 989: 979: 969: 959: 886: 867: 830: 826: 810: 800: 799: 767: 766: 703: 690: 672: 668: 639: 638: 536: 535: 529:null hypothesis 523: 513: 503: 497: 487: 481: 471: 434: 421: 408: 395: 382: 350: 349: 337: 330: 323: 316: 309: 302: 295: 280: 272: 264: 251: 243: 235: 227: 214: 206: 198: 190: 154: 146: 138: 125: 117: 109: 69: 22:William Cochran 12: 11: 5: 1584: 1582: 1574: 1573: 1563: 1562: 1558: 1557: 1534:10.1086/519795 1508: 1473: 1437: 1436: 1435: 1415: 1378: 1372: 1354: 1351: 1350: 1349: 1342: 1339: 1328: 1327: 1324: 1320: 1319: 1316: 1312: 1311: 1308: 1304: 1303: 1300: 1246: 1245: 1242: 1239: 1236: 1233: 1229: 1228: 1225: 1222: 1219: 1216: 1212: 1211: 1208: 1205: 1202: 1199: 1195: 1194: 1191: 1188: 1185: 1182: 1165: 1162: 1144: 1141: 1102: 1096: 1095: 1084: 1081: 1078: 1075: 1072: 1069: 1065: 1061: 1055: 1052: 1049: 1045: 1042: 1039: 1034: 1018: 1017: 1006: 1002: 996: 992: 986: 982: 976: 972: 966: 962: 956: 951: 948: 945: 942: 939: 935: 929: 926: 923: 918: 915: 912: 908: 904: 901: 898: 893: 889: 885: 882: 879: 874: 870: 864: 859: 855: 849: 844: 841: 838: 834: 829: 823: 817: 813: 807: 803: 796: 793: 790: 787: 782: 779: 776: 756: 755: 744: 741: 738: 735: 732: 729: 726: 723: 719: 715: 710: 706: 702: 697: 693: 688: 684: 681: 678: 675: 671: 667: 664: 661: 658: 655: 652: 649: 646: 628: 627: 616: 613: 610: 607: 604: 600: 596: 593: 590: 587: 584: 581: 578: 575: 572: 569: 566: 563: 559: 555: 552: 549: 546: 543: 518: 508: 501: 492: 485: 476: 467: 461: 460: 449: 446: 441: 437: 431: 428: 424: 420: 415: 411: 405: 402: 398: 394: 389: 385: 379: 374: 371: 368: 364: 360: 357: 343:test statistic 335: 328: 321: 314: 307: 300: 293: 285: 284: 281: 278: 273: 270: 265: 262: 257: 253: 252: 249: 244: 241: 236: 233: 228: 225: 220: 216: 215: 212: 207: 204: 199: 196: 191: 188: 183: 179: 178: 175: 172: 169: 166: 156: 155: 152: 147: 144: 139: 136: 131: 127: 126: 123: 118: 115: 110: 107: 102: 98: 97: 94: 91: 88: 68: 65: 26:Peter Armitage 13: 10: 9: 6: 4: 3: 2: 1583: 1572: 1569: 1568: 1566: 1553: 1549: 1544: 1539: 1535: 1531: 1528:(3): 559–75. 1527: 1523: 1519: 1512: 1509: 1504: 1500: 1496: 1492: 1488: 1484: 1477: 1474: 1469: 1465: 1461: 1457: 1453: 1449: 1442: 1439: 1421: 1416: 1412: 1408: 1404: 1400: 1396: 1392: 1388: 1384: 1379: 1375: 1373:0-471-36093-7 1369: 1365: 1361: 1360:Agresti, Alan 1357: 1356: 1352: 1348: 1345: 1344: 1340: 1338: 1336: 1325: 1322: 1321: 1317: 1314: 1313: 1309: 1306: 1305: 1301: 1298: 1297: 1294: 1291: 1289: 1285: 1281: 1278:, the choice 1277: 1273: 1269: 1265: 1261: 1257: 1253: 1243: 1240: 1237: 1234: 1231: 1230: 1226: 1223: 1220: 1217: 1214: 1213: 1209: 1206: 1203: 1200: 1197: 1196: 1192: 1189: 1186: 1183: 1181: 1180: 1177: 1175: 1171: 1163: 1161: 1159: 1155: 1150: 1142: 1140: 1138: 1134: 1130: 1126: 1122: 1118: 1114: 1110: 1105: 1101: 1082: 1076: 1073: 1070: 1059: 1050: 1032: 1023: 1022: 1021: 1004: 1000: 994: 990: 984: 980: 974: 970: 964: 960: 954: 949: 946: 943: 940: 937: 933: 927: 924: 921: 916: 913: 910: 906: 902: 899: 891: 887: 883: 880: 872: 868: 862: 857: 853: 847: 842: 839: 836: 832: 827: 821: 815: 811: 805: 801: 794: 788: 765: 764: 763: 761: 760:decomposition 742: 739: 733: 727: 721: 717: 708: 704: 700: 695: 691: 682: 676: 669: 665: 659: 653: 647: 637: 636: 635: 633: 614: 608: 605: 602: 594: 591: 588: 579: 576: 573: 567: 564: 561: 553: 550: 547: 534: 533: 532: 530: 525: 522: 517: 512: 507: 500: 496: 491: 484: 480: 475: 470: 466: 447: 439: 435: 429: 426: 422: 418: 413: 409: 403: 400: 396: 387: 383: 377: 372: 369: 366: 362: 358: 355: 348: 347: 346: 344: 339: 334: 331: +  327: 324: =  320: 313: 310: +  306: 303: +  299: 296: =  292: 282: 277: 274: 269: 266: 261: 258: 255: 254: 248: 245: 240: 237: 232: 229: 224: 221: 218: 217: 211: 208: 203: 200: 195: 192: 187: 184: 181: 180: 176: 173: 170: 167: 165: 164: 161: 151: 148: 143: 140: 135: 132: 129: 128: 122: 119: 114: 111: 106: 103: 100: 99: 95: 92: 89: 87: 86: 83: 81: 77: 74: 66: 64: 62: 59: 56: 52: 47: 43: 39: 35: 31: 28:, is used in 27: 23: 19: 1525: 1521: 1511: 1486: 1482: 1476: 1451: 1447: 1441: 1426:. Retrieved 1386: 1382: 1363: 1331: 1292: 1279: 1271: 1263: 1249: 1167: 1154:alternatives 1146: 1136: 1132: 1128: 1124: 1120: 1116: 1112: 1103: 1099: 1098:The weights 1097: 1019: 757: 629: 526: 520: 515: 510: 505: 498: 494: 489: 482: 478: 473: 468: 464: 462: 340: 332: 325: 318: 311: 304: 297: 290: 288: 275: 267: 259: 246: 238: 230: 222: 209: 201: 193: 185: 159: 149: 141: 133: 120: 112: 104: 79: 72: 70: 67:Introduction 55:case-control 45: 37: 20:, named for 17: 15: 1190:Genotype AA 1187:Genotype Aa 1184:Genotype aa 762:, yielding 34:association 1483:Biometrics 1448:Biometrics 1428:6 February 1383:Biometrics 1353:References 1276:codominant 463:where the 341:The trend 1268:recessive 1198:Controls 1170:genotypes 1060:∼ 934:∑ 925:− 907:∑ 900:− 884:− 833:∑ 728:⁡ 677:⁡ 666:⁡ 648:⁡ 577:⋯ 419:− 363:∑ 359:≡ 1565:Category 1552:17701901 1362:(2002). 1341:See also 1260:dominant 1172:at some 1109:powerful 51:genotype 1543:1950838 1503:3001775 1468:3001616 1411:9423247 1403:2533494 1335:p-value 1299:Weights 488: − 338:, etc. 317:, and 58:genetic 1550:  1540:  1501:  1466:  1409:  1401:  1370:  1326:−4.67 1323:0,1,2 1315:0,1,1 1307:1,1,0 1256:allele 1215:Cases 289:where 219:A = 2 182:A = 1 130:A = 2 101:A = 1 96:B = 3 1499:JSTOR 1464:JSTOR 1423:(PDF) 1399:JSTOR 1318:−2.1 1310:1.85 1258:a is 1174:locus 1149:power 174:B = 3 171:B = 2 168:B = 1 93:B = 2 90:B = 1 1548:PMID 1430:2009 1407:PMID 1368:ISBN 1244:120 1232:Sum 1193:Sum 514:and 256:Sum 177:Sum 24:and 16:The 1538:PMC 1530:doi 1491:doi 1456:doi 1391:doi 1227:60 1210:60 345:is 1567:: 1546:. 1536:. 1526:81 1524:. 1520:. 1497:. 1487:11 1485:. 1462:. 1452:10 1450:. 1405:. 1397:. 1387:53 1385:. 1241:50 1238:40 1235:30 1224:30 1221:20 1218:10 1207:20 1204:20 1201:20 743:0. 634:, 583:Pr 542:Pr 336:21 329:11 315:13 308:12 301:11 283:N 242:23 234:22 226:21 205:13 197:12 189:11 153:23 145:22 137:21 124:13 116:12 108:11 63:. 1554:. 1532:: 1505:. 1493:: 1470:. 1458:: 1434:– 1432:. 1413:. 1393:: 1376:. 1280:t 1272:t 1264:t 1137:B 1133:t 1129:t 1125:B 1121:B 1117:B 1113:k 1104:i 1100:t 1083:. 1080:) 1077:1 1074:, 1071:0 1068:( 1064:N 1054:) 1051:T 1048:( 1044:r 1041:a 1038:V 1033:T 1005:, 1001:) 995:j 991:C 985:i 981:C 975:j 971:t 965:i 961:t 955:k 950:1 947:+ 944:i 941:= 938:j 928:1 922:k 917:1 914:= 911:i 903:2 897:) 892:i 888:C 881:N 878:( 873:i 869:C 863:2 858:i 854:t 848:k 843:1 840:= 837:i 828:( 822:N 816:2 812:R 806:1 802:R 795:= 792:) 789:T 786:( 781:r 778:a 775:V 740:= 737:) 734:0 731:( 725:E 722:= 718:) 714:) 709:2 705:R 701:, 696:1 692:R 687:| 683:T 680:( 674:E 670:( 663:E 660:= 657:) 654:T 651:( 645:E 615:. 612:) 609:k 606:= 603:B 599:| 595:1 592:= 589:A 586:( 580:= 574:= 571:) 568:1 565:= 562:B 558:| 554:1 551:= 548:A 545:( 521:i 519:2 516:N 511:i 509:1 506:N 502:1 499:R 495:i 493:2 490:N 486:2 483:R 479:i 477:1 474:N 469:i 465:t 448:, 445:) 440:1 436:R 430:i 427:2 423:N 414:2 410:R 404:i 401:1 397:N 393:( 388:i 384:t 378:k 373:1 370:= 367:i 356:T 333:N 326:N 322:1 319:C 312:N 305:N 298:N 294:1 291:R 279:3 276:C 271:2 268:C 263:1 260:C 250:2 247:R 239:N 231:N 223:N 213:1 210:R 202:N 194:N 186:N 150:N 142:N 134:N 121:N 113:N 105:N 80:k 73:k 46:k 38:k

Index

William Cochran
Peter Armitage
categorical data analysis
association
Pearson chi-squared test
genotype
case-control
genetic
association studies
contingency table
test statistic
null hypothesis
iterated expectation
decomposition
powerful
power
alternatives
null hypothesis
genotypes
locus
mode of inheritance
allele
dominant
recessive
codominant
complex diseases
genome-wide association studies
p-value
List of analyses of categorical data
Agresti, Alan

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