Polygenic risk score, psychosocial environment and the risk of attention-deficit/hyperactivity disorder

Søren D Østergaard,Preben B Mortensen,Anders D Børglum,Bjarni Jóhann Vilhjálmsson,Esben Agerbo,David M Hougaard,Thomas D Als,Betina B Trabjerg,Thomas Werge,Marie Bækvad-Hansen,Florian Privé,Clara Albiñana Climent,Jonas Bybjerg-Grauholm,Ole Mors,Ditte Demontis,Merete Nordentoft

doi:10.1038/s41398-020-01019-6

Abstract

The objective of the present study was to investigate whether the polygenic liability for attention-deficit/hyperactivity disorder (ADHD) and the psychosocial environment impact the risk of ADHD in interaction or independently of each other. We conducted a register- and biobank-based cohort study of 13,725 individuals with ADHD and 20,147 randomly drawn population-based controls. These 33,872 cohort members were genotyped on the Infinium PsychChip v1.0 array (Illumina). Subsequently, we calculated the polygenic risk score (PRS) for ADHD and extracted register data regarding the following risk factors pertaining to the psychosocial environment for each cohort member at the time of birth: maternal/paternal history of mental disorders, maternal/paternal education, maternal/paternal work status, and maternal/paternal income. We used logistic regression analyses to assess the main effects of the PRS for ADHD and the psychosocial environment on the risk of ADHD. Subsequently, we evaluated whether the effect of the PRS and the psychosocial environment act independently or in interaction upon the risk of ADHD. We found that ADHD was strongly associated with the PRS (odds ratio: 6.03, 95%CI: 4.74–7.70 for highest vs. lowest 2% liability). All risk factors pertaining to the psychosocial environment were associated with an increased risk of ADHD. These associations were only slightly attenuated after mutual adjustments. We found no statistically significant interaction between the polygenic liability and the psychosocial environment upon the risk of ADHD. In conclusion, we found main effects of both polygenic liability and risk factors pertaining to the psychosocial environment on the risk of ADHD—in the expected direction.

Highlights

Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset neurodevelopmental disorder with a prevalence of approximately 5–7% among children/adolescents[1,2]
Statistics The associations between the polygenic risk score (PRS) for attention-deficit/hyperactivity disorder (ADHD), the risk factors related to the psychosocial environment and ADHD were assessed using logistic regression
For the main effects of the PRS for ADHD and the risk factors related to the psychosocial environment, crude odds ratios for ADHD adjusted for sex and year of birth were computed

Summary

Introduction

Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset neurodevelopmental disorder with a prevalence of approximately 5–7% among children/adolescents[1,2]. The specific causes of ADHD remain largely unknown, but a number of twin studies have suggested that the disorder is among the most heritable Recent studies focusing on both common- and rare genetic variants have identified genes associated with ADHD14–16. A number of early adverse psychosocial factors have consistently been linked to ADHD17–21. There is a growing body of literature supporting the hypothesis that genetic and psychosocial risk factors do have direct effects on the risk of ADHD, and interact[22,23,24]. Most studies on the combined effect of genetic and psychosocial risk

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Conclusion