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

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

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

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. © Institute of Mathematical Statistics, 2009.
Original languageEnglish (US)
Pages (from-to)489-502
Number of pages14
JournalStatistical Science
Volume24
Issue number4
DOIs
StatePublished - Nov 2009
Externally publishedYes

Fingerprint

Dive into the research topics of 'Analysis of Case-Control Association Studies: SNPs, Imputation and Haplotypes'. Together they form a unique fingerprint.

Cite this