Skip to main content
NCBI home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1991 Jul;49(1):76–87.

Estimation of morbid risk and age at onset with missing information.

L A Cupples 1, N Risch 1, L A Farrer 1, R H Myers 1
PMCID: PMC1683228  PMID: 1829582

Abstract

Investigators of genetic illnesses are currently employing life-table techniques to estimate the lifetime risk of disease and the age-at-onset distribution. This methodology assumes that onset ages are known for affected individuals and that censoring ages are known for unaffected individuals. We extend these methods to incorporate affected individuals with unknown onset ages and unaffected persons with unknown censoring ages and illustrate how conventional life-table methods can produce seriously biased estimates, particularly of lifetime risk. The methodology is not restricted to genetic illnesses and can be applied to more complex illnesses with unknown etiology. We present an example for Huntington disease, which is generally assumed to be a Mendelian autosomal dominant disease, yielding estimates of lifetime risk of .503 +/- .70 and mean onset age of 47.7 +/- 3.1 years for offspring with a single affected parent. When conventional life-table techniques are employed, these estimates are .238 +/- .032 and 43.2 +/- 2.2.

Full text

PDF
76

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adams P., Falek A., Arnold J. Huntington disease in Georgia: age at onset. Am J Hum Genet. 1988 Nov;43(5):695–704. [PMC free article] [PubMed] [Google Scholar]
  2. Breitner J. C., Silverman J. M., Mohs R. C., Davis K. L. Familial aggregation in Alzheimer's disease: comparison of risk among relatives of early-and late-onset cases, and among male and female relatives in successive generations. Neurology. 1988 Feb;38(2):207–212. doi: 10.1212/wnl.38.2.207. [DOI] [PubMed] [Google Scholar]
  3. Chase G. A., Folstein M. F., Breitner J. C., Beaty T. H., Self S. G. The use of life tables and survival analysis in testing genetic hypotheses, with an application to Alzheimer's disease. Am J Epidemiol. 1983 May;117(5):590–597. doi: 10.1093/oxfordjournals.aje.a113581. [DOI] [PubMed] [Google Scholar]
  4. Chidambaram A., Chakravarti A., Ferrell R. E., Iyengar S. Estimating the age-at-onset function using life-table methods. Genet Epidemiol. 1988;5(4):255–263. doi: 10.1002/gepi.1370050407. [DOI] [PubMed] [Google Scholar]
  5. Conneally P. M. Huntington disease: genetics and epidemiology. Am J Hum Genet. 1984 May;36(3):506–526. [PMC free article] [PubMed] [Google Scholar]
  6. Cupples L. A., Terrin N. C., Myers R. H., D'Agostino R. B. Using survival methods to estimate age-at-onset distributions for genetic diseases with an application to Huntington disease. Genet Epidemiol. 1989;6(2):361–371. doi: 10.1002/gepi.1370060206. [DOI] [PubMed] [Google Scholar]
  7. Elandt-Johnson R. C. Age-at-onset distribution in chronic diseases. A life table approach to analysis of family data. J Chronic Dis. 1973 Aug;26(8):529–545. doi: 10.1016/0021-9681(73)90004-0. [DOI] [PubMed] [Google Scholar]
  8. Farrer L. A., Conneally P. M. A genetic model for age at onset in Huntington disease. Am J Hum Genet. 1985 Mar;37(2):350–357. [PMC free article] [PubMed] [Google Scholar]
  9. Farrer L. A., Conneally P. M., Yu P. L. The natural history of Huntington disease: possible role of "aging genes". Am J Med Genet. 1984 May;18(1):115–123. doi: 10.1002/ajmg.1320180115. [DOI] [PubMed] [Google Scholar]
  10. Farrer L. A., Myers R. H., Cupples L. A., St George-Hyslop P. H., Bird T. D., Rossor M. N., Mullan M. J., Polinsky R., Nee L., Heston L. Transmission and age-at-onset patterns in familial Alzheimer's disease: evidence for heterogeneity. Neurology. 1990 Mar;40(3 Pt 1):395–403. doi: 10.1212/wnl.40.3_part_1.395. [DOI] [PubMed] [Google Scholar]
  11. Heimbuch R. C., Matthysse S., Kidd K. K. Estimating age-of-onset distributions for disorders with variable onset. Am J Hum Genet. 1980 Jul;32(4):564–574. [PMC free article] [PubMed] [Google Scholar]
  12. MORTON N. E. Genetic tests under incomplete ascertainment. Am J Hum Genet. 1959 Mar;11(1):1–16. [PMC free article] [PubMed] [Google Scholar]
  13. Meyer J. M., Eaves L. J. Estimating genetic parameters of survival distributions: a multifactorial model. Genet Epidemiol. 1988;5(4):265–275. doi: 10.1002/gepi.1370050408. [DOI] [PubMed] [Google Scholar]
  14. Mohs R. C., Breitner J. C., Silverman J. M., Davis K. L. Alzheimer's disease. Morbid risk among first-degree relatives approximates 50% by 90 years of age. Arch Gen Psychiatry. 1987 May;44(5):405–408. doi: 10.1001/archpsyc.1987.01800170019003. [DOI] [PubMed] [Google Scholar]
  15. Myers R. H., Cupples L. A., Schoenfeld M., D'Agostino R. B., Terrin N. C., Goldmakher N., Wolf P. A. Maternal factors in onset of Huntington disease. Am J Hum Genet. 1985 May;37(3):511–523. [PMC free article] [PubMed] [Google Scholar]
  16. Myers R. H., Goldman D., Bird E. D., Sax D. S., Merril C. R., Schoenfeld M., Wolf P. A. Maternal transmission in Huntington's disease. Lancet. 1983 Jan 29;1(8318):208–210. doi: 10.1016/s0140-6736(83)92587-4. [DOI] [PubMed] [Google Scholar]
  17. Myers R. H., Madden J. J., Teague J. L., Falek A. Factors related to onset age of Huntington disease. Am J Hum Genet. 1982 May;34(3):481–488. [PMC free article] [PubMed] [Google Scholar]
  18. Pericak-Vance M. A., Elston R. C., Conneally P. M., Dawson D. V. Age-of-onset heterogeneity in Huntington disease families. Am J Med Genet. 1983 Jan;14(1):49–59. doi: 10.1002/ajmg.1320140109. [DOI] [PubMed] [Google Scholar]
  19. Risch N. Estimating morbidity risks with variable age of onset: review of methods and a maximum likelihood approach. Biometrics. 1983 Dec;39(4):929–939. [PubMed] [Google Scholar]
  20. Thompson W. D., Weissman M. M. Quantifying lifetime risk of psychiatric disorder. J Psychiatr Res. 1981;16(2):113–126. doi: 10.1016/0022-3956(81)90026-1. [DOI] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES