Genetics in psychiatry: Methods, clinical applications and future perspectives

Abstract

Psychiatric disorders and related traits have a demonstrated genetic component, with heritability estimated by twin studies generally between 80% and 40%. Their pathogenesis is complex and multi-determined: environmental factors interact with a polygenic architecture, making difficult the development of models able to stratify patients or predict mental health outcomes. Despite this difficult challenge, relevant progress has been made in the field of psychiatric genetics in recent years. This review aims to present the main current methods in psychiatric genetics, their output, limitations, clinical applications, and possible future developments. Genome-wide association studies (GWASs) performed in increasingly large samples have led to the identification of replicated genetic loci associated with the risk of major psychiatric disorders, including schizophrenia and mood disorders. Statistical and biological approaches have been developed to improve our understanding of the etiopathogenetic mechanisms behind genome-wide significant associations, as well as for estimating the cumulative effect of risk variants at the individual level and the genetic overlap between different disorders, as pleiotropy is the rule rather than the exception. Clinical applications are available in the pharmacogenetics field. The main issues that remain to be addressed include improving ethnic diversity in genetic studies and the optimization of statistical power through methodological improvements, such as the definition of dimensional phenotypes with specific biological correlates and the integration of different types of omics data.

When Dad’s Stress Gets under Kid’s Skin—Impacts of Stress on Germline Cargo and Embryonic Development

“…Pervasive psychological stress imposes an escalating burden on healthcare and society [1], as it emerges as a significant risk factor for the development of neuropsychiatric and neurophysiological conditions, many of which exhibit a hereditary element [2]. Nevertheless, the inheritance of these conditions cannot be fully accounted for by Mendelian inheritance of gene variants.…”

Tools of genomic medicine for clinical practice: The example of psychiatry

“…La investigación genética en psiquiatría agrupa aquellos estudios que buscan demostrar la existencia de la herencia en la etiopatogenia de los trastornos psiquiátricos; los que analizan modelos de herencia y aquellos que tratan de establecer mecanismos de acción genéticos de los síntomas y los trastornos mentales (Cuadro 2). La evidencia demuestra que el grado de contribución de las variantes genéticas es dinámico y considerable para los diferentes trastornos psiquiátricos [39]. Así por ejemplo, algunos estudios en gemelos revelan una heredabilidad del 80% para esquizofrenia [42] y trastorno afectivo bipolar [43], y de alrededor de 50% para el trastorno depresivo mayor [44].…”

Pharmacogenomic Diversity in Psychiatry: Challenges and Opportunities in Africa

“…Genetic polymorphisms located within or near pharmacologically relevant candidate genes and combined scores from these variants [16][17][18][19][20] have shown association with individuals' reactions to psychiatric medications [21]. In patients with bipolar disorder (BD), a high polygenic loading for schizophrenia (SCZ) or major depressive disorder (MDD) is significantly associated with poor response to lithium treatment [22][23][24], and incorporating clinical variables in conjunction with the polygenic scores has enhanced the ability to predict the response to lithium treatment in these patients [25][26][27]. Similarly, in patients with MDD, the polygenic scores for neuroticism and openness personality traits were associated with the likelihood of remission to selective serotonin reuptake inhibitors (SSRIs) treatment [28].…”

“…Similarly, in patients with MDD, the polygenic score (PGS) for neuroticism and openness personality were associated with SSRIs treatment remission (13). Incorporating clinical predictors in conjunction with PGSs has enhanced the ability to predict the response to lithium treatment in patients with BD (14)(15)(16).…”