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. 2020 Oct 2;10(1):335.
doi: 10.1038/s41398-020-01019-6.

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

Søren D Østergaard  1   2   3 , Betina B Trabjerg  3   4 , Thomas D Als  3   5 , Clara Albiñana Climent  3   4 , Florian Privé  3   4 , Bjarni Jóhann Vilhjálmsson  3   4 , Marie Bækvad-Hansen  3   6 , Jonas Bybjerg-Grauholm  3   6 , David M Hougaard  3   6 , Merete Nordentoft  3   7 , Thomas Werge  3   8 , Ditte Demontis  3   5   9 , Preben B Mortensen  3   4   10 , Anders D Børglum  3   5   9 , Ole Mors  2   3   11 , Esben Agerbo  12   13   14
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Polygenic risk score, psychosocial environment and the risk of attention-deficit/hyperactivity disorder

Søren D Østergaard et al. Transl Psychiatry. .

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.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1. ADHD Polygenic Risk Score Distributions.
Comparison between individuals with ADHD and uniform randomly population-based individuals.
Fig. 2
Fig. 2. The crude and adjusted effect of the polygenic risk score for ADHD on the risk of ADHD.
*crude adjustment: the estimates are only adjusted for sex and year of birth. The polygenic risk score for ADHD was divided into 50 groups each representing 2% of the distribution of the PRS for ADHD among the randomly drawn population controls.
Fig. 3
Fig. 3. Polygenic Risk Score and Parental Psychosocial Environment.
Odds ratio for ADHD across levels of parental risk factors and polygenic risk score quartiles.
See this image and copyright information in PMC

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