Challenges for genetic analysis in the 21st century: localizing and characterizing genes for common complex diseases and their quantitative risk factors

The optimal study design and method of analysis for genetic studies of complex traits have received much attention of late. Most previous works on this topic have assumed that investigators will study a single focal disease trait. In this paper, we approach the question of study design from the perspective of the inherently multivariate study which includes a variety of quantitative risk factors as well as one or more common complex disease traits. We conclude that a sample of randomly ascertained extended pedigrees provides both analytical power and flexibility, permitting profitable investigation of numerous traits using both linkage and linkage-disequilibrium based methods.