Using genes and environments to define asthma and related phenotypes: applications to multivariate data

It is generally accepted that asthma is a complex disease for which clinical manifestation is not attributed to the simple expression of a particular gene. Rather, asthma reflects the culmination of a pathogenic process that is not well understood, but seems to involve many genetic and environmental factors. One of the main points of consensus of the large scientific literature is that asthma is not clearly defined. Most research is based upon a cluster of asthma-related phenotypes for which the clinical and aetiological boundaries are unclear. Part of the reason we are here today concerns the urgency of coordinating our research efforts to define useful phenotypes. Progress in understanding the genetics of asthma is intimately related to progress in understanding what we are measuring and how genetic and environmental influences mediate the associations between these measures. The purpose of this paper is to highlight some applications using multivariate approaches to study the genetics of asthma. These include, for example, differentiating between aetiological and clinical heterogeneity, incorporating new advancements to detect quantitative trait loci, differential expression of genetic effects during pathogenesis and whether the same sources of genetic variation are expressed for ‘normal’ and ‘extreme’ phenotypes. Although a full description of these applications would be too lengthy for this presentation, some examples will be described.