Approaches to Studying Human Genetics

It is well-established that genetic factors influence sleep-related traits and chronotype—which is the behavioral manifestation of the genetically encoded molecular oscillator known as the circadian clock (Gehrman et al. Psychiatr Clin North Am 38:667–681, 2015; Rosensweig and Green Eur J Neurosci 51:139–165, 2020; Veatch et al. Lancet Neurol 16:158–170, 2017). Advances in molecular and computational analysis methods, along with the evolution of biobanks in recent years, have provided an explosion of knowledge into the underlying genetic mechanisms contributing to variability in sleep/wake behavior as well as expression of sleep disorders (Cade et al. Genome Med 13:136, 2021; Dashti et al. Nat Commun 10:1100, 2019a; Jasen et al. Nat Genet 51:394–403, 2019; Lane et al. Nat Genet 49:274–281, 2017; Wang et al. Nat Commun 10:3503, 2019). However, several technical (and ethical) challenges remain that must be considered when undertaking human genetic studies. These include the need for a solid understanding of the assumptions being made with the various approaches implemented and the limitations of these approaches that impede the translation of findings. This chapter will offer a broad overview of approaches currently applied in the field of genetic epidemiology as well as background information that should inform future studies aimed at deciphering the complicated genetic architecture underlying expression of sleep and circadian traits in humans.