Quantifying Genetic Risk in Attention-Deficit/Hyperactivity Disorder

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PRS presents a good tool to measure genetic loading of ADHD variants, suggesting which cases are most likely to persist.
PRS presents a good tool to measure genetic loading of ADHD variants, suggesting which cases are most likely to persist.

A pattern of symptomatic persistence in attention-deficit hyperactive disorder (ADHD) beyond childhood and adolescence is strongly associated with a higher genetic risk variant load measured by polygenic risk scores (PRS), researchers reported in JAMA Psychiatry.1 Higher PRS for ADHD, like the presence of greater multimorbidity in some ADHD children, provided markers of greater persistence of ADHD beyond the early childhood years.

Diagnosis of ADHD is most commonly made in childhood, and 15% of these cases are likely to continue to exhibit symptoms into adulthood. As the remission rate for ADHD that persists to adulthood is only 35%,2,3 this subgroup of ADHD presents a significant challenge.

A cohort of 9757 children between the ages of 4 and 17 with ADHD (4968 boys, 4789 girls) from the Avon Longitudinal Study of Parents and Children was used for the study base. Data collected at multiple points in time pointed to 4 subtypes of ADHD trajectories identified as low (82.6%), intermediate (7.7%), childhood-limited (5.8%), and persistent (3.9%).

In the current study, the investigators found that the subgroups of children with persistent ADHD made up 40% and those with childhood-limited ADHD made up 60% of the total group (9.7%) that initially showed elevated symptoms. Higher PRS and the presence of comorbid neurodevelopmental conditions including low IQ, problems with social development, pragmatic language disorders, and behavioral issues corresponded to increased risk of persistent ADHD, but not of the other disorders.

While at baseline, the ratio of boys to girls was slightly higher overall, there were significant differences in distribution across trajectories. The majority of children in the persistent group were boys (72.9%), followed by the intermediate (63%) and child-limited (62.3%), and dipping to a slight minority in the low group (48%), suggesting that boys with ADHD are more likely to show symptoms that persist into adulthood.

The persistent trajectory of ADHD symptoms correlated with a 4-fold higher risk of ADHD within families than was found among those who had ADHD limited to childhood. The notion that ADHD is inherited has also been supported in twin studies as well as in genomic studies, which have identified both common risk alleles and rare mutations.4-8 The inherited rate of ADHD has been shown in previous studies to range from 71% to 90%.5

The authors contend that PRS presents a good tool to measure genetic loading of ADHD variants, suggesting which cases are most likely to persist. The potential of using PRS scores to identify children with ADHD whose symptoms are most likely to persist throughout childhood may offer the opportunity for treatment that prevents the continuation of symptoms into adulthood.

References

  1. Riglin L, Collishaw S, Thapar AK, et al. Association of genetic risk variants with attention-deficit/hyperactivity disorder trajectories in the general population. JAMA Psychiatry. 2016;73(12):1285-1292. doi:10.1001/jamapsychiatry.2016.2817.
  2. Thapar A, Cooper M. Attention deficit hyperactivity disorder. Lancet. 2016;387:1240-1250.
  3. Faraone SV, Biederman J, Mick E. The age-dependent decline of attention deficit hyperactivity disorder: a meta-analysis of follow-up studies. Psychol Med. 2006;36:159-165.
  4. Pingault JB, Viding E, Galera C, et al. Genetic and environmental influences on the developmental course of attention-deficit/hyperactivity disorder symptoms from childhood to adolescence. JAMA Psychiatry. 2015;72:651-658.
  5. Thapar A, Cooper M, Eyre O, et al. What have we learnt about the causes of ADHD? J Child Psychol Psychiatry. 2013;54:3-16.
  6. Chang Z, Lichtenstein P, Asherson PJ, et al. Developmental twin study of attention problems: high heritabilities throughout development. JAMA Psychiatry. 2013;70:311-318.
  7. Franke B, Faraone SV, Asherson P, et al. The genetics of attention deficit/hyperactivity disorder in adults, a review. Mol Psychiatry. 2012;17(10):960-87.
  8. Larsson H, Asherson P, Chang Z, et al. Genetic and environmental influences on adult attention deficit hyperactivity disorder symptoms: a large Swedish population-based study of twins. Psychol Med. 2013;43:197-207.
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