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A Nelson-Aalen estimate of the incidence rates of early-onset Alzheimer’s disease associated with the presenilin-1 gene. (English) Zbl 1061.62571

Summary: We analyse, in a probabilistic setting, R. G. Newcombe’s [Ann. Hum. Genetics 45, 375-385 (1981)] life table method of estimating rates of onset of high-penetrance single-gene disorders, and extend this to a counting process model for individual life histories, including movement between risk groups arising from genetic testing and onset in relatives. A key result is that estimates of rates of onset at any age x must be conditioned only on information available when subjects were age x, even though their later life histories might be available to the investigator. This determines the data that must be included in pedigrees.
We derive a Nelson-Aalen-type estimate of a function of the rate of onset, and show that when all that is known is that the persons in the study inherited a mutation with probability 1/2, the function estimated is bounded. In practice, the treatment of censored observations or the methods of ascertainment might cause the estimate to exceed this bound, which results in infinite estimates of the rate of onset but might be a useful diagnostic check on the presence of these features. We summarise the literature on mutations in the Presenilin-1 (PSEN-1) gene, associated with early-onset Alzheimer’s disease (EOAD), and from published pedigrees we estimate rates of onset of EOAD.

MSC:

62P10 Applications of statistics to biology and medical sciences; meta analysis
62N02 Estimation in survival analysis and censored data
92D10 Genetics and epigenetics
92C50 Medical applications (general)
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References:

[1] DOI: 10.2143/AST.30.1.504627 · doi:10.2143/AST.30.1.504627
[2] DOI: 10.1080/10920277.1999.10595777 · Zbl 1082.62540 · doi:10.1080/10920277.1999.10595777
[3] DOI: 10.1098/rstb.1997.0087 · doi:10.1098/rstb.1997.0087
[4] DOI: 10.1017/S1357321700003524 · doi:10.1017/S1357321700003524
[5] DOI: 10.1002/(SICI)1098-1004(1997)10:3&lt;186::AID-HUMU2&gt;3.0.CO;2-H · doi:10.1002/(SICI)1098-1004(1997)10:3<186::AID-HUMU2>3.0.CO;2-H
[6] Neurobiology of Aging 21 pp S25– (2000)
[7] Neuro Report 8 pp 1537– (1997)
[8] Folia Neuropathologica 37 pp 415– (1999)
[9] Survival analysis: Techniques for censored and truncated data (1997) · Zbl 0871.62091
[10] DOI: 10.1016/0304-3940(96)12587-8 · doi:10.1016/0304-3940(96)12587-8
[11] DOI: 10.1016/S0022-510X(98)00219-6 · doi:10.1016/S0022-510X(98)00219-6
[12] Clinical Genetics 50 pp 281– (1996)
[13] Neurobiology of Aging 21 pp S176– (2000)
[14] DOI: 10.1002/ana.410400614 · doi:10.1002/ana.410400614
[15] DOI: 10.1007/s004060050028 · doi:10.1007/s004060050028
[16] DOI: 10.1038/sj.ejhg.5200423 · doi:10.1038/sj.ejhg.5200423
[17] Alzheimer’s Reports 3 pp 227– (2000)
[18] DOI: 10.1093/biomet/81.4.701 · Zbl 0810.62008 · doi:10.1093/biomet/81.4.701
[19] DOI: 10.1136/jnnp.64.1.44 · doi:10.1136/jnnp.64.1.44
[20] DOI: 10.1136/jmg.29.4.239 · doi:10.1136/jmg.29.4.239
[21] DOI: 10.1016/S0166-2236(96)01030-2 · doi:10.1016/S0166-2236(96)01030-2
[22] DOI: 10.1007/s004390050688 · doi:10.1007/s004390050688
[23] DOI: 10.1002/ana.410410618 · doi:10.1002/ana.410410618
[24] DOI: 10.1016/S0002-9440(10)65094-8 · doi:10.1016/S0002-9440(10)65094-8
[25] DOI: 10.1212/WNL.54.5.1103 · doi:10.1212/WNL.54.5.1103
[26] DOI: 10.1016/S0925-4439(00)00028-4 · doi:10.1016/S0925-4439(00)00028-4
[27] DOI: 10.1086/301672 · doi:10.1086/301672
[28] DOI: 10.1093/brain/120.3.491 · doi:10.1093/brain/120.3.491
[29] Neurobiology of Aging 21 pp S176– (2000)
[30] DOI: 10.1016/S0304-3940(97)00603-4 · doi:10.1016/S0304-3940(97)00603-4
[31] DOI: 10.1212/WNL.55.10.1590 · doi:10.1212/WNL.55.10.1590
[32] Counting processes and survival analysis (1991) · Zbl 0727.62096
[33] DOI: 10.1016/S0304-3940(96)13138-4 · doi:10.1016/S0304-3940(96)13138-4
[34] Impact of modern genetics on insurance (1999)
[35] Lancet 346 pp 440– (1995)
[36] DOI: 10.1097/00001756-199810050-00034 · doi:10.1097/00001756-199810050-00034
[37] Human Mutation 14 pp 90– (1999)
[38] Journal of Risk and Insurance 66 pp 531– (2000)
[39] Human molecular genetics, second edition (1999)
[40] DOI: 10.1086/302702 · doi:10.1086/302702
[41] DOI: 10.1097/00001756-199602290-00029 · doi:10.1097/00001756-199602290-00029
[42] Neurobiology of Aging 21 (2000)
[43] DOI: 10.1001/archneur.57.4.485 · doi:10.1001/archneur.57.4.485
[44] DOI: 10.1212/WNL.52.3.566 · doi:10.1212/WNL.52.3.566
[45] DOI: 10.1016/0021-9681(73)90004-0 · doi:10.1016/0021-9681(73)90004-0
[46] DOI: 10.1136/jmg.35.8.672 · doi:10.1136/jmg.35.8.672
[47] DOI: 10.1016/S0140-6736(95)92809-X · doi:10.1016/S0140-6736(95)92809-X
[48] Human Molecular Genetics 8 pp 1539– (1999)
[49] DOI: 10.1002/1531-8249(200101)49:1&lt;125::AID-ANA21&gt;3.0.CO;2-1 · doi:10.1002/1531-8249(200101)49:1<125::AID-ANA21>3.0.CO;2-1
[50] DOI: 10.1097/00019052-200008000-00004 · doi:10.1097/00019052-200008000-00004
[51] DOI: 10.1097/00001756-199902250-00011 · doi:10.1097/00001756-199902250-00011
[52] Progress in Neurobiology 60 pp 363– (1999)
[53] DOI: 10.1038/375754a0 · doi:10.1038/375754a0
[54] DOI: 10.1002/(SICI)1098-1004(1998)11:3&lt;183::AID-HUMU1&gt;3.0.CO;2-J · doi:10.1002/(SICI)1098-1004(1998)11:3<183::AID-HUMU1>3.0.CO;2-J
[55] Human Mutation pp 591– (1998)
[56] DOI: 10.1002/ana.410400225 · doi:10.1002/ana.410400225
[57] DOI: 10.1016/S0006-3223(99)00301-7 · doi:10.1016/S0006-3223(99)00301-7
[58] DOI: 10.1016/S0197-4580(98)00020-7 · doi:10.1016/S0197-4580(98)00020-7
[59] DOI: 10.1038/35014735 · doi:10.1038/35014735
[60] DOI: 10.1093/hmg/7.1.43 · doi:10.1093/hmg/7.1.43
[61] Human Molecular Genetics 5 pp 1449– (1996) · doi:10.1093/hmg/5.Supplement_1.1449
[62] DOI: 10.1093/hmg/4.12.2363 · doi:10.1093/hmg/4.12.2363
[63] DOI: 10.1038/nm0498-452 · doi:10.1038/nm0498-452
[64] DOI: 10.1038/ng1095-219 · doi:10.1038/ng1095-219
[65] Lancet 347 pp 1560– (1996)
[66] Lancet 346 pp 1040– (1995)
[67] Neuro Report 10 pp 2255– (1999)
[68] American Journal of Human Genetics 59 pp A252– (1996)
[69] DOI: 10.1038/376775a0 · doi:10.1038/376775a0
[70] DOI: 10.1086/302553 · doi:10.1086/302553
[71] Neurobiology of Aging 17 pp S14– (1996)
[72] Neuro Report 7 pp 1582– (1996)
[73] DOI: 10.1007/s004390050288 · doi:10.1007/s004390050288
[74] DOI: 10.1212/WNL.45.1.80 · doi:10.1212/WNL.45.1.80
[75] Human Mutation 16 pp 95– (2000)
[76] DOI: 10.1212/WNL.55.10.1577 · doi:10.1212/WNL.55.10.1577
[77] Annals Génét 41 pp 149– (1998)
[78] DOI: 10.1016/S0304-3940(01)01498-7 · doi:10.1016/S0304-3940(01)01498-7
[79] DOI: 10.1038/13383 · doi:10.1038/13383
[80] Neurobiology of Aging 17 (1996)
[81] DOI: 10.1136/jnnp.68.2.220 · doi:10.1136/jnnp.68.2.220
[82] DOI: 10.1001/archneur.56.1.65 · doi:10.1001/archneur.56.1.65
[83] DOI: 10.1016/S0304-3940(97)00569-7 · doi:10.1016/S0304-3940(97)00569-7
[84] DOI: 10.1093/hmg/4.12.2373 · doi:10.1093/hmg/4.12.2373
[85] Neuro Report 9 pp 217– (1998)
[86] DOI: 10.1016/S0140-6736(96)90261-5 · doi:10.1016/S0140-6736(96)90261-5
[87] DOI: 10.1074/jbc.M007183200 · doi:10.1074/jbc.M007183200
[88] Nature Medicine 1 pp 848– (1995)
[89] DOI: 10.1002/ana.410400619 · doi:10.1002/ana.410400619
[90] Genetic tests and future need for long-term care in the UK: report of a Work Group of the Continuing Care Conference Genetic Tests and Long-term Care Study Group (1999)
[91] Human Mutation (Mutation in Brief) 141 (1997)
[92] DOI: 10.1001/archneur.55.5.698 · doi:10.1001/archneur.55.5.698
[93] DOI: 10.1212/WNL.48.4.1118 · doi:10.1212/WNL.48.4.1118
[94] DOI: 10.1002/(SICI)1098-1004(1998)11:3&lt;216::AID-HUMU6&gt;3.0.CO;2-F · doi:10.1002/(SICI)1098-1004(1998)11:3<216::AID-HUMU6>3.0.CO;2-F
[95] Statistical models based on counting processes (1993) · Zbl 0769.62061
[96] DOI: 10.1097/00001756-199608120-00033 · doi:10.1097/00001756-199608120-00033
[97] DOI: 10.1002/(SICI)1098-1004(199911)14:5&lt;433::AID-HUMU10&gt;3.0.CO;2-K · doi:10.1002/(SICI)1098-1004(199911)14:5<433::AID-HUMU10>3.0.CO;2-K
[98] DOI: 10.1006/neur.1996.0028 · doi:10.1006/neur.1996.0028
[99] DOI: 10.1097/00001756-199512000-00071 · doi:10.1097/00001756-199512000-00071
[100] An introduction to human molecular genetics (1999)
[101] Human Mutation 13 pp 256– (1999)
[102] DOI: 10.1111/j.1469-1809.1981.tb00351.x · doi:10.1111/j.1469-1809.1981.tb00351.x
[103] Clinical Genetics 53 pp 469– (1998)
[104] Neurology 41 pp 62– (1991)
[105] DOI: 10.1080/10920277.2001.10595985 · Zbl 1083.62537 · doi:10.1080/10920277.2001.10595985
[106] DOI: 10.1016/S0304-3940(97)00950-6 · doi:10.1016/S0304-3940(97)00950-6
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