Quantitative trait locus mapping methods for complex phenotypes: The state of the science

In the past decade, there has been phenomenal progress in molecular and statistical genetic methods for localizing quantitative trait loci. Because of these advances, we can anticipate a long period of active genetic research in which the genes influencing human quantitative variability will be mapped and their effects accurately evaluated. In this paper, I review the current state-of-the-science in statistical genetic methods for quantitative trait linkage analysis. The advantages and disadvantages of the major competing methods are described and evaluated both analytically and via computer simulation. Particular attention is paid to the optimal design of human family studies for localizing genes of small to moderate effect. Additionally, methods and strategies are described for dealing with the most important complications of quantitative variation including the joint analysis of discrete and continuous traits, genotype X environment interaction, and epistasis. Examples of successful quantitative trait linkage analysis will be provided.