This chapter discusses the methodological considerations surrounding linkage and association studies as well as results of both approaches as they relate to sleep and sleep disorders. The initial study of familial advanced sleep phase syndrome (FASPS) that showed it to be inherited in an autosomal dominant fashion was a linkage study on a large family with over 20 affected individuals. For the most part, the risk of narcolepsy to relatives of an affected individual is low (1-2%), albeit higher than the average population risk. Restless leg syndrome (RLS) is fairly common, with the prevalence estimated to be between 1.2 and 15% depending on the population. Complex phenotypes are influenced by multiple genetic and non-genetic factors. These phenotypes cluster in families do not follow any clear mode of inheritance. Complex phenotypes are divided into two classes: continuous and categorical. Genome-wide association study (GWAS) has been recently employed in studying sleep phenotypes.

This chapter discusses the organization of human sleep by the brain mechanisms and specific sleep disorders that lead to disturbances in the brain mechanisms. Non-rapid eye movement (NREM) sleep is controlled by brainstem oscillators whose activation leads to the multiple physiological accompaniments of the NREM state. The dream is the unusual mental content that often accompanies REM sleep. As humans transition from wakefulness to sleep, characteristic physiological changes include decreases in respiratory rate, heart rate, and blood pressure. The domain of the insomnias benefits from thoughtful differential diagnosis, as the causation may be both multiple and obscure. The insomnia complaints that are comorbid with medical disorders include both sleep disturbances caused by medical symptoms, and also those sleep disturbances caused by the pathophysiology underlying the medical condition. Restless leg syndrome (RLS) and periodic limb movements of sleep (PLMS) are considered as sleep disorders.