Skip Navigation



Biostatistics Advance Access published online on February 24, 2006
Biostatistics, doi:10.1093/biostatistics/kxj021
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
7/3/486    most recent
kxj021v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Zeng, D.
Right arrow Articles by Bray, M. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zeng, D.
Right arrow Articles by Bray, M. S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Received December 5, 2005
Accepted February 7, 2006

Article

Efficient semiparametric estimation of haplotype-disease associations in case-cohort and nested case-control studies

D. Zeng 1, D. Y. Lin 1 *, C. L. Avery 2, K. E. North 2, and M. S. Bray 3

1 Department of Biostatistics, CB# 7420, University of North Carolina, Chapel Hill, NC 27599-7420, U.S.A.
2 Department of Epidemiology, CB# 7435, University of North Carolina, Chapel Hill, NC 27599-7420, U.S.A.
3 Department of Pediatrics, Baylor College of Medicine, Houston, TX, U.S.A.

* To whom correspondence should be addressed.
D. Y. Lin, E-mail: lin{at}bios.unc.edu


  Abstract

Estimating the effects of haplotypes on the age of onset of a disease is an important step toward the discovery of genes that influence complex human diseases. A haplotype is a specific sequence of nucleotides on the same chromosome of an individual and can only be measured indirectly through the genotype. We consider cohort studies which collect genotype data on a subset of cohort members through case-cohort or nested case-control sampling. We formulate the effects of haplotypes and possibly time-varying environmental variables on the age of onset through a broad class of semiparametric regression models. We construct appropriate nonparametric likelihoods, which involve both finite- and infinite-dimensional parameters. The corresponding nonparametric maximum likelihood estimators are shown to be consistent, asymptotically normal and asymptotically efficient. Consistent variance-covariance estimators are provided, and efficient and reliable numerical algorithms are developed. Simulation studies demonstrate that the asymptotic approximations are accurate in practical settings and that case-cohort and nested case-control designs are highly cost-effective. An application to a major cardiovascular study is provided.

Keywords: Age of onset; Association studies; Censoring; Haplotype effects; Nonparametric likelihood; Proportional hazards; Semiparametric efficiency; Single nucleotide polymorphisms; Survival data.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Cancer Res.Home page
A. DeMichele, R. Gray, M. Horn, J. Chen, R. Aplenc, W. P. Vaughan, and M. S. Tallman
Host Genetic Variants in the Interleukin-6 Promoter Predict Poor Outcome in Patients with Estrogen Receptor-Positive, Node-Positive Breast Cancer
Cancer Res., May 15, 2009; 69(10): 4184 - 4191.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
M. Siedlinski, C. C. van Diemen, D. S. Postma, J. M. Vonk, and H. M. Boezen
Superoxide dismutases, lung function and bronchial responsiveness in a general population
Eur. Respir. J., May 1, 2009; 33(5): 986 - 992.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
J. Galanter, S. Choudhry, C. Eng, S. Nazario, J. R. Rodriguez-Santana, J. Casal, A. Torres-Palacios, J. Salas, R. Chapela, H. G. Watson, et al.
ORMDL3 Gene Is Associated with Asthma in Three Ethnically Diverse Populations
Am. J. Respir. Crit. Care Med., June 1, 2008; 177(11): 1194 - 1200.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
Q. Cai, N. Kataoka, C. Li, W. Wen, J. R. Smith, Y.-T. Gao, X. O. Shu, and W. Zheng
Haplotype Analyses of CYP19A1 Gene Variants and Breast Cancer Risk: Results from the Shanghai Breast Cancer Study
Cancer Epidemiol. Biomarkers Prev., January 1, 2008; 17(1): 27 - 32.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. Hughes, O. Agbaje, R. L. Bowen, D. L. Holliday, J. A. Shaw, S. Duffy, and J. L. Jones
Matrix Metalloproteinase Single-Nucleotide Polymorphisms and Haplotypes Predict Breast Cancer Progression
Clin. Cancer Res., November 15, 2007; 13(22): 6673 - 6680.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.