Abstract
Importance Polygenic scores (PGS) are widely used to characterize genetic liability for heritable mental disorders, including attention-deficit/hyperactivity disorder (ADHD). However, little is known about the effects of having a low burden of genetic liability for ADHD, including whether this functions as a protective or resilience factor for psychopathology and functional outcomes in later life. Understanding the consequences of being on the “positive” side of the PGS distribution may shed light on mechanisms of risk and resilience for ADHD.
Objective To examine the association of low PGS for ADHD and functional outcomes in adulthood. To also examine whether these associations are moderated by early childhood maltreatment.
Design Wave IV of the National Longitudinal Study of Adolescent to Adult Health (Add Health), conducted between 2007 and 2008. Data analyses were conducted from March 2019 to April 2019.
Setting Population-based sample in the United States.
Participants Add Health adults aged 24 to 32 for whom genotypic and phenotypic data were available (n=7,190).
Exposure PGS for ADHD were used to examine associations for ADHD and across a range of functional outcomes in adulthood.
Main Outcome and Measures Regression models tested the association of ADHD PGS and adult functional outcomes, including cognition, educational attainment, mental health (e.g., depression) and physical health (e.g., body mass index). Interactions between ADHD PGS and childhood maltreatment were examined for each outcome variable.
Results Individuals at the lowest end of the ADHD PGS distribution exhibited a two-fold risk reduction (95% CI=2.8-5.3%) of ADHD relative to the observed prevalence in Add Health (8.3%). Individuals with low ADHD PGS (<20th percentile) demonstrated consistently superior adult functional outcomes relative to majority of individuals along the ADHD PGS distribution, including those who were in the medium and high ADHD PGS groups. No interactions between ADHD PGS and childhood maltreatment emerged.
Conclusions and Relevance Low ADHD PGS may be a robust protective factor in not only the genesis of ADHD, but also of negative functional outcomes that are typically disrupted among adults with ADHD. There was no evidence that low PGS confers resilience to childhood maltreatment, however. Psychiatric PGS may hold crucial information for the purposes of clinical prediction, beyond simply risk and the absence of risk.
Question Does having a low polygenic score (PGS) for ADHD reduce one’s risk for ADHD relative to the incidence rate in the population; are individuals with low PGS more resilient to childhood maltreatment?
Findings In this longitudinal study of 7,190 adolescents followed into adulthood, individuals with low PGS had a two-fold risk reduction for ADHD (4.1%) relative to the observed incidence of ADHD (8.3%) and showed superior functional outcomes relative to those with medium and high PGS. No evidence of resilience was detected.
Meaning Low PGS may be a protective factor in not only the genesis of ADHD, but also for negative functional outcomes in adulthood.