Statistical Science

Analysis of Case-Control Association Studies: SNPs, Imputation and Haplotypes

Nilanjan Chatterjee, Yi-Hau Chen, Sheng Luo, and Raymond J. Carroll

Full-text: Open access

Abstract

Although prospective logistic regression is the standard method of analysis for case-control data, it has been recently noted that in genetic epidemiologic studies one can use the “retrospective” likelihood to gain major power by incorporating various population genetics model assumptions such as Hardy–Weinberg-Equilibrium (HWE), gene–gene and gene–environment independence. In this article we review these modern methods and contrast them with the more classical approaches through two types of applications (i) association tests for typed and untyped single nucleotide polymorphisms (SNPs) and (ii) estimation of haplotype effects and haplotype–environment interactions in the presence of haplotype-phase ambiguity. We provide novel insights to existing methods by construction of various score-tests and pseudo-likelihoods. In addition, we describe a novel two-stage method for analysis of untyped SNPs that can use any flexible external algorithm for genotype imputation followed by a powerful association test based on the retrospective likelihood. We illustrate applications of the methods using simulated and real data.

Article information

Source
Statist. Sci., Volume 24, Number 4 (2009), 489-502.

Dates
First available in Project Euclid: 20 April 2010

Permanent link to this document
https://projecteuclid.org/euclid.ss/1271770344

Digital Object Identifier
doi:10.1214/09-STS297

Mathematical Reviews number (MathSciNet)
MR2779339

Zentralblatt MATH identifier
1329.62421

Keywords
Case-control studies Empirical-Bayes genetic epidemiology haplotypes model averaging model robustness model selection retrospective studies shrinkage

Citation

Chatterjee, Nilanjan; Chen, Yi-Hau; Luo, Sheng; Carroll, Raymond J. Analysis of Case-Control Association Studies: SNPs, Imputation and Haplotypes. Statist. Sci. 24 (2009), no. 4, 489--502. doi:10.1214/09-STS297. https://projecteuclid.org/euclid.ss/1271770344


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