Combined polygenic risk scores of different psychiatric traits predict general and specific psychopathology in childhood

Abstract

Background: Polygenic risk scores (PRSs) operationalize genetic propensity toward a particular mental disorder and hold promise as early predictors of psychopathology, but before a PRS can be used clinically, explanatory power must be increased and the specificity for a psychiatric domain established. To enable early detection, it is crucial to study these psychometric properties in childhood. We examined whether PRSs associate more with general or with specific psychopathology in school-aged children. Additionally, we tested whether psychiatric PRSs can be combined into a multi-PRS score for improved performance. Methods: We computed 16 PRSs based on GWASs of psychiatric phenotypes, but also neuroticism and cognitive ability, in mostly adult populations. Study participants were 9,247 school-aged children from three population-based cohorts of the DREAM-BIG consortium: ALSPAC (UK), The Generation R Study (Netherlands), and MAVAN (Canada). We associated each PRS with general and specific psychopathology factors, derived from a bifactor model based on self-report and parental, teacher, and observer reports. After fitting each PRS in separate models, we also tested a multi-PRS model, in which all PRSs are entered simultaneously as predictors of the general psychopathology factor. Results: Seven PRSs were associated with the general psychopathology factor after multiple testing adjustment, two with specific externalizing and five with specific internalizing psychopathology. PRSs predicted general psychopathology independently of each other, with the exception of depression and depressive symptom PRSs. Most PRSs associated with a specific psychopathology domain, were also associated with general child psychopathology. Conclusions: The results suggest that PRSs based on current GWASs of psychiatric phenotypes tend to be associated with general psychopathology, or both general and specific psychiatric domains, but not with one specific psychopathology domain only. Furthermore, PRSs can be combined to improve predictive ability. PRS users should therefore be conscious of nonspecificity and consider using multiple PRSs simultaneously, when predicting psychiatric disorders.

Portability of Polygenic Risk Scores for Sleep Duration, Insomnia and Chronotype in 33,493 Individuals

“…This finding is in agreement with earlier studies in the field of PRSs. Indeed, earlier literature shows that the PRSs usually have low explanatory power on the traits of interest, and even an R 2 of less than 1% are often reported [ 16 , 17 ]. In addition, it is important to note that genetic variants generally add up to around 10–50 percent of the phenotypic variance [ 14 ] and provide insight particularly on the genetic component of natural variation in sleep and individual circadian timing.…”

Advances in problematic usage of the internet research – A narrative review by experts from the European network for problematic usage of the internet

“…Impulsivity, which has been linked to PUI, is highly heritable and genetic have been linked to impulsivity and substance use [119,120]. Additionally, polygenic risk scores (PRSs) for neuroticism, generalized anxiety, ADHD, schizophrenia and cognitive ability have been associated with internalizing psychopathology in young children [121], and these may be useful for predicting psychopathology in children. Recently, the heritability of neuroticism was found to increase when socioeconomic status and education were taken into account [122], which may also be relevant for PUI.…”

Linkage of whole genome sequencing and administrative health data in autism: A proof of concept study

“…Data could also support distinct genetic mechanisms towards psychiatric vulnerability in autism. For example, emerging data suggest there is: (1) an inverse correlation between high‐impact de novo variants and autism polygenic scores—(i.e., genetic contributors to autism seem to include either high polygenic likelihood OR high‐impact rare variants; Antaki et al, 2022; Warrier et al, 2022), (2) there are general effects of autism polygenic scores on psychopathology broadly (i.e., high polygenic scores may increase likelihood for developmental and mental health differences; Kember et al, 2021; Neumann et al, 2022), and (3) that in neuropsychiatric disorders, individuals with inherited genetic risk factors may be more likely to experience socioeconomic/environmental adversity (Ratanatharathorn et al, 2021; Wolstencroft et al, 2022). Together, these findings set the stage for future studies examining the types of psychiatric conditions, service needs, and barriers faced by those with genetic forms of autism, as well as the relative contributions of environmental factors, comorbid medical conditions, and rare/common and inherited/de novo variants, to help anticipate mental health care needs in autistic youth.…”