Discovering Multilocus Associations with Complex Pain Phenotypes
This chapter covers statistical complexity in pain genetics. It discusses the analysis of the multiple genetic markers within one gene locus. The choice of the best analysis between these markers and phenotype depends on the relationships between these markers - the linkage disequilibrium, the functional consequences of the variants and the presence of other ungenotyped functional variants within close proximity of the genotyped variants. As an example of such approaches, the chapter also discusses a recently proposed statistical method for testing a joint effect of multiple genetic variants termed "Composite Haplotype Method" (CHM). The method is applied for an analysis of the gene locus of the μ-opioid receptor. The chapter also describes a new method for a two-stage analysis. Performance of the two-stage approach with rare variants requires further investigation and appears worthwhile to undertake.
