title: Use of diplotypes - matched haplotype pairs from homologous chromosomes - in gene-disease association studies.
abstract: Alleles, genotypes and haplotypes (combinations of alleles) have been widely used in gene-disease association studies. More recently, association studies using diplotypes (haplotype pairs on homologous chromosomes) have become increasingly common. This article reviews the rationale of the four types of association analyses and discusses the situations in which diplotype-based analyses are more powerful than the other types of association analyses. Haplotype-based association analyses are more powerful than allele-based association analyses, and diplotype-based association analyses are more powerful than genotype-based analyses. In circumstances where there are no interaction effects between markers and where the criteria for Hardy-Weinberg Equilibrium (HWE) are met, the larger sample size and smaller degrees of freedom of allele-based and haplotype-based association analyses make them more powerful than genotype-based and diplotype-based association analyses, respectively. However, under certain circumstances diplotype-based analyses are more powerful than haplotype-based analysis.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, United States ; VA Connecticut Healthcare System, West Haven Campus, Connecticut, United States.
authors.forename: Lingjun
authors.initials: L
authors.lastname: Zuo
authors.affiliation: Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Johnson City, Tennessee, United States.
authors.forename: Kesheng
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, United States ; VA Connecticut Healthcare System, West Haven Campus, Connecticut, United States.
authors.forename: Xingguang
authors.initials: X
authors.lastname: Luo
keywords: Hardy-Weinberg equilibrium; association analysis; diplotype; genotypes; haplotype; interaction effects
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