This paper explores the interpretation and use of polygenic risk scores (PRSs). We argue that PRSs generally do not directly embody causal information. Nonetheless, they can assist us in tracking other causal relationships concerning genetic effects. Although their purely predictive/correlational use is important, it is this tracking feature that contributes to their potential usefulness in other applications, such as genetic dissection, and their use as controls, which allow us, indirectly, to "see" more clearly the role of environmental variables.

Prosper Lucas (1808–1885) is a unique figure in the history of psychiatric genetics. A physician-alienist, he authored one of the most important books on human genetics in the mid-19th century cited frequently by Darwin: the 1,500 page treatise—Philosophical and Physiological Treatise on Natural Heredity (1847–1850). This book contained a novel theory of the nature of inheritance and a detailed review of the heredity of a range of human traits and disorders, including various forms of insanity. Lucas postulated four forms of (...) heredity (direct, crossed, indirect, and atavistic), supported the importance of hereditary factors in insanity, accepted the inheritance of acquired characteristics, considered it important to examine both ancestors and collateral relatives, and recognized that heredity could influence both primary insanity and insanity secondary to other medical conditions. He reviewed the then available literature on most major forms of insanity including separate sections on hallucinations and suicidal monomania. The literature consisted of case reports of unusual families with high concentrations of illness. Lucas advocated for the homogeneity of transmission of forms of illness in families but recognized that—just as the form of illness could evolve within individuals over time—it could change forms when transmitted between relatives. (shrink)