New insights from the last decade of research in psychiatric genetics: discoveries, challenges and clinical implications

Abstract

Psychiatric genetics has made substantial progress in the last decade, providing new insights into the genetic etiology of psychiatric disorders, and paving the way for precision psychiatry, in which individual genetic profiles may be used to personalize risk assessment and inform clinical decision‐making. Long recognized to be heritable, recent evidence shows that psychiatric disorders are influenced by thousands of genetic variants acting together. Most of these variants are commonly occurring, meaning that every individual has a genetic risk to each psychiatric disorder, from low to high. A series of large‐scale genetic studies have discovered an increasing number of common and rare genetic variants robustly associated with major psychiatric disorders. The most convincing biological interpretation of the genetic findings implicates altered synaptic function in autism spectrum disorder and schizophrenia. However, the mechanistic understanding is still incomplete. In line with their extensive clinical and epidemiological overlap, psychiatric disorders appear to exist on genetic continua and share a large degree of genetic risk with one another. This provides further support to the notion that current psychiatric diagnoses do not represent distinct pathogenic entities, which may inform ongoing attempts to reconceptualize psychiatric nosology. Psychiatric disorders also share genetic influences with a range of behavioral and somatic traits and diseases, including brain structures, cognitive function, immunological phenotypes and cardiovascular disease, suggesting shared genetic etiology of potential clinical importance. Current polygenic risk score tools, which predict individual genetic susceptibility to illness, do not yet provide clinically actionable information. However, their precision is likely to improve in the coming years, and they may eventually become part of clinical practice, stressing the need to educate clinicians and patients about their potential use and misuse. This review discusses key recent insights from psychiatric genetics and their possible clinical applications, and suggests future directions.

Dimensions of psychopathology associated with psychotic-like experiences: Findings from the network analysis in a nonclinical sample

“…The authors of this study found a total of 10 genes to be commonly associated with the risk of OCD, schizophrenia, bipolar disorder, and autism spectrum disorder. Altogether, these findings might suggest that cross-disorder genetic backgrounds may underlie shared correlates within a higher-order structure of psychopathology [55].…”

Precision medicine in complex diseases—Molecular subgrouping for improved prediction and treatment stratification

“…Most psychiatric disorders have a high heritability, with estimates between 40% and 80% [50], and are highly polygenic [51]. Lately, there has been a large increase in discoveries of genetic variants associated with psychiatric disorders [50], followed by the development of PRS-based tools [51]. However, PRS for psychiatric disorders explain relatively small proportions of the liability of each disorder, and the current PRS are still not clinically useful [52].…”

Evidence for a shared genetic contribution to loneliness and Borderline Personality Disorder

“…In recent years, the study of genetic risk factors has received increasing attention in the study of inter-individual differences in mental health (Andreassen, Hindley, Frei, & Smeland, 2023). Twin and family studies aim to estimate the influence of genetic and environmental influences on the variation of traits or disorder risk using the information on genetic relatedness and shared family environment (Shih, Belmonte, & Zandi, 2004).…”

“…For psychiatric symptoms and disorders, the so called SNP-based heritability, i.e. the variance explained by the common variants assessed in a GWAS, usually accounts for around one third of the heritabilities estimated in twin studies (Andreassen et al, 2023). Besides insights into specific genes and pathways involved in disease etiology, GWAS also allow the estimation to what degree the association signal, and thereby the underlying genetic factors, are shared between disorders and traits.…”