Complex Trait Genetics

Quantitative genetics is concerned with the inheritance of those differences between individuals that are of degree rather than of kind (quantitative rather than qualitative). Such differences are seen for most human complex traits (e.g. depression, cognitive abilities or attention problems). When traits are classified into dichotomies (e.g. the population is characterized by affected and unaffected individuals), a quantitative distribution of liability may be assumed to model their inheritance. This course aims to provide the theoretical understanding of the inheritance of quantitative differences in behaviour, behavioural disorders, endophenotypes (e.g. blood pressure or brain volumes) underlying disease traits (e.g. hypertension or schizophrenia). Quantitative differences, as far as they are inherited, depend on genes with on average small effects and are usually influenced by gene differences at many loci. Consequently these genes cannot be identified by Mendelian segregation ratios (though they are subject to the laws of Mendelian transmission). The methods of quantitative genetics are characterized by studies of large populations and families / twins and by the fact that the nature of quantitative differences requires the measurement (and not just the classification) of individuals. The extension of Mendelian genetics into quantitative genetics will be made in two stages: the genetic properties of populations (population genetics) and the inheritance of measurements (biometrical genetics). Quantitative genetics is now merging with molecular genetics and the last part of this course will be devoted to methods for the localization and characterization of genes causing quantitative variation and an introduction of epigenetics.