Quantitative and molecular genetics of child and adolescent mental health disorders: Recent advances, knowledge gaps and directions for future research

Quantitative and molecular genetic research studies have already contributed substantially to increase the understanding of the links and boundaries across different child and adolescent mental health conditions and between child and adult forms of psychopathology. Several findings have been replicated across quantitative and molecular genetic methods, and across clinical and population ‐ based samples. An important task for future quantitative and moleculargeneticresearchistoadvancetheunderstanding of howchildhood psychopathology unfoldsinto adult forms of psychopathology, and to reveal the etiologic relationships across different forms of psychopathology. In the years to come, we can expect further breakthroughs in the genetics of child and adolescent mental health disorders to come from converging evidence across different quantitative and molecular genetic methods.

have been replicated across quantitative and molecular genetic methods, and across clinical and population-based samples. An important task for future quantitative and molecular genetic research is to advance the understanding of how childhood psychopathology unfolds into adult forms of psychopathology, and to reveal the etiologic relationships across different forms of psychopathology. In the years to come, we can expect further breakthroughs in the genetics of child and adolescent mental health disorders to come from converging evidence across different quantitative and molecular genetic methods.

K E Y W O R D S
developmental psychopathology, mental health disorders, molecular genetics, quantitativegenetics EDITORIAL Various child and adolescent mental health disorders were for a long time primarily considered as separate conditions. From a historical perspective, there has also been a strict boundary between child and adult psychiatry. During the last decade, this view has slowly changed, to some extent owing to quantitative (family, twin and adoption studies) and molecular (Genome-wide association studies and its downstream applications) genetic research demonstrating shared genetic risks across virtually all forms of psychopathology that have been assessed.
This editorial aims to provide an overview of recent advances from quantitative and molecular genetic studies regarding links between different mental health disorders and developmental trajectories of psychopathology from childhood to adulthood, as well as to highlight remaining knowledge gaps and directions for future research.

Quantitative genetics
Many readers of JCPP Advances know that the key question of contemporary quantitative genetics of child and adolescent mental health disorders and traits is not "if" genetic factors are important, but rather "how" genetic factors influence different forms of child and adolescent psychopathology across development. Longitudinal quantitative genetic studies have over the past decades addressed important questions about the underlying genetic and environmental contributions to developmental trajectories of psychopathology. Most of these studies have explored development of these phenotypes from childhood to adolescence. The general pattern of findings indicate, if we put it simply, that both stable and dynamic genetic risk factors influence psychopathology over the developmental course from childhood to adolescence (Hannigan et al., 2017). The stable component of underlying genetic risks suggest that childhood and adolescent forms of psychopathology are genetically linked. The dynamic components suggest that the set of genetic variants accounting for the onset of psychopathology may differ from those accounting for the persistence and remission of psychopathology. An important task for future quantitative genetic research is to extend this research into adulthood to advance our understanding of how childhood psychopathology unfolds into adult forms of psychopathology. This is now possible given that several twin datasets (e.g.,. TEDS) were established about 25 years ago, and many of these data sources now contain detailed longitudinal assessments of psychopathology from early childhood via adolescence into adulthood.
Numerous bivariate quantitative genetic studies have, over the past decade, estimated genetic correlations between different mental health disorders (Martin et al., 2018). These findings generally support the hypothesis that many forms of psychopathology across the life-span correlate in part due to genetic factors. Findings from more recent multivariate quantitative genetic studies suggest that comorbidity across different forms of psychopathology is, at least in part, due to a genetically influenced general psychopathology factor (often referred to as the P-factor) (Lahey et al., 2011), as well as by genetic sharing across sub-dimensions of psychopathology (e.g., internalizing and externalizing problems). Important questions regarding the general factor of psychopathology and internalizing and externalizing subdimensions remain to be addressed, such as development from childhood and adolescence into adulthood. Increasing use of sophisticated multivariate quantitative genetic approaches has the potential to generate a more in-depth understanding of the etiological (genetic and environmental) relationships underlying not just psychopathology, but also a broader disorder spectrum that includes physical conditions which frequently co-occur with psychopathology. Some aspects of these questions will be addressed in the first special issue of JCPP Advances, which is scheduled for late 2021 and will focus on the interplay between mental and physical health.

Molecular genetics
Genome-wide association studies ( A key characteristic of more recent molecular genetic studies is that they, much like quantitative genetics, have moved from bivariate to multivariate approaches (e.g., genomic structural equation modeling  It is important to highlight that the number of PGS studies has increased rapidly in recent years and clarity around methodology and interpretation of results is much needed, such as generalizability to individuals of non-European ancestry. Implementation of sophisticated study designs (e.g., within-siblings designs) and analyses (e.g., mediation analyses), coupled with larger and more diverse samples, have the potential to help uncover the mechanisms underlying identified PGS associations and improve clarity around interpretation.

CONCLUSIONS AND FUTURE DIRECTIONS
Quantitative and molecular genetic research have already contributed substantially to an increased understanding of links and In the years to come, we can expect further breakthroughs in the genetics of child and adolescent mental health disorders to come from converging evidence across different quantitative and molecular genetic methods. There is, however, still a lack of clinical translation and more work is needed from this research tradition to truly fill its potential and in the future have a real impact for individuals with mental health disorders, their careers, and clinicians.

ACKNOWLEDGMENTS
The author thanks Joanna Martin, PhD, of Cardiff University, as well as Isabell Brikell, PhD, Ebba Du Rietz, PhD and Mark Taylor, PhD, all at Karolinska Institutet.

CONFLICT OF INTEREST
Henrik Larsson reports receiving grants from Shire Pharmaceuticals; personal fees from and serving as a speaker for Shire Pharmaceuticals and Evolan Pharma AB outside the submitted work; and sponsorship for a conference on attention-deficit/hyperactivity disorder from Shire Pharmaceuticals outside the submitted work.