Modeling hazard functions in families

Genetic Epidemiology
K Siegmund, B McKnight

Abstract

A genetic frailty model is presented for censored age of onset data in nuclear families where individuals carrying a genetic susceptibility gene have an increased risk of becoming affected. We use maximum likelihood via the EM algorithm to estimate the genetic relative risk and the allele frequency under a dominant susceptibility type and a proportional hazards model. When sampling is from a disease registry, likelihood corrections are necessary for reducing bias in the parameter estimates. In these biased samples, the full conditional likelihood is approximated by a likelihood conditional on the proband's age of onset. For unbiased samples, simulations show the distributions of the estimates are similar under both a semiparametric and the correctly specified parametric likelihoods. For biased samples, simulations under the approximate conditional likelihood show the median estimates of the allele frequency and genetic relative risk tend to under- and overestimate, respectively, the true values; however, the approximation is better for rarer allele frequencies (0.0033 vs. 0.01). In practice, large samples or more complex ascertainment corrections are recommended. Using the approximate conditional likelihood on familial breast c...Continue Reading

References

Jul 1, 1990·Environmental Health Perspectives·W MackD C Thomas
Jan 1, 1989·Genetic Epidemiology·R C Elston, V T George
Jan 1, 1988·Genetic Epidemiology·J M Meyer, L J Eaves
May 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·B NewmanM C King
Dec 1, 1986·Theoretical Population Biology·W J Ewens, N C Shute
Nov 2, 1994·Journal of the National Cancer Institute·J R DalingN S Weiss
May 21, 1998·Genetic Epidemiology·H LiE M Wijsman
Mar 1, 1954·British Journal of Cancer·P ARMITAGE, R DOLL
Mar 1, 1980·Environmental Science & Technology·M P Helme, W J Pienta

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Citations

Dec 22, 1999·Genetic Epidemiology·G A ChaseL R Goldin
Jul 9, 2010·Veterinary Medicine International·Mélisa VeilletteStéphan G Reebs
Feb 3, 2004·Statistics in Medicine·Tron A MogerHåkon K Gjessing
Jan 28, 2003·Genetic Epidemiology·L Hsu
Jul 13, 2019·European Journal of Human Genetics : EJHG·John Michael O RanolaBrian H Shirts
Sep 13, 2011·Statistical Science : a Review Journal of the Institute of Mathematical Statistics·Heping Zhang

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