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Bootstrap confidence intervals for relative risk parameters in affected‐sib‐pair data
Author(s) -
Cordell Heather J.,
Carpenter James R.
Publication year - 2000
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/(sici)1098-2272(200002)18:2<157::aid-gepi5>3.0.co;2-w
Subject(s) - confidence interval , statistics , resampling , mathematics , robust confidence intervals , confidence distribution , point estimation , coverage probability , nuisance parameter , nominal level , econometrics , estimator
In affected‐sib‐pair (ASP) studies, parameters such as the locus‐specific sibling relative risk, λ s , may be estimated and used to decide whether or not to continue the search for susceptibility genes. Typically, a maximum likelihood point estimate of λ s is given, but since this estimate may have substantial variability, it is of interest to obtain confidence limits for the true value of λ s . While a variety of methods for doing this exist, there is considerable uncertainty over their reliability. This is because the discrete nature of ASP data and the imposition of genetic “possible triangle” constraints during the likelihood maximization mean that asymptotic results may not apply. In this paper, we use simulation to evaluate the reliability of various asymptotic and simulation‐based confidence intervals, the latter being based on a resampling, or bootstrap approach. We seek to identify, from the large pool of methods available, those methods that yield short intervals with accurate coverage probabilities for ASP data. Our results show that many of the most popular bootstrap confidence interval methods perform poorly for ASP data, giving coverage probabilities much lower than claimed. The test‐inversion, profile‐likelihood, and asymptotic methods, however, perform well, although some care is needed in choice of nuisance parameter. Overall, in simulations under a variety of different genetic hypotheses, we find that the asymptotic methods of confidence interval evaluation are the most reliable, even in small samples. We illustrate our results with a practical application to a real data set, obtaining confidence intervals for the sibling relative risks associated with several loci involved in type 1 diabetes. Genet. Epidemiol. 18:157–172, 2000. © 2000 Wiley‐Liss, Inc.