Association of Genetic Risk Variants With Attention-Deficit/Hyperactivity Disorder Trajectories in the General Population

Lucy Riglin, Stephen Collishaw, Ajay K Thapar, Soren Dalsgaard, Kate Langley, George Davey Smith, Evie Stergiakouli, Barbara Maughan, Michael O'Donovan, Anita Thapar

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

Importance. Attention Deficit Hyperactivity Disorder (ADHD) is a highly heritable neurodevelopmental disorder that shows clinical and genetic overlap with other childhood neurodevelopmental problems. ADHD symptom levels typically decline across childhood/adolescence, although remain elevated for some individuals. The determinants of symptom persistence and decline are not yet fully understood. Objective. Test the hypothesis that genetic risk variant load for ADHD (indexed by polygenic risk scores (PRS)), but not for other psychiatric disorders, is associated with population-based ADHD symptom trajectories across childhood/adolescence. As a secondary objective, examine whether higher ADHD genetic liability is correlated with childhood multi-morbidity (total number of additional neurodevelopmental problems). Design, setting and participants. A prospective population-based cohort design, The Avon Longitudinal Study of Parents and Children (ALSPAC): ongoing data collection since 1990. 14,701 children were alive at 1 year, 9575 individuals with data on ADHD symptoms at multiple time-points were included. Main Outcome and Measure(s). ADHD symptom trajectories from ages 4 to 17 years (7 time-points). The primary exposure variables, PRS, were generated in ALSPAC using genome-wide association study results from the Psychiatric Genomics Consortium. Childhood multi-morbidity scores (age 7-9 years) were measured by total impairments (0-4) in four domains known to share genetic liability with ADHD: (i) IQ, (ii) Social-communication, (iii) Pragmatic language, and (iv) Conduct. Results. Four ADHD symptom trajectories were identified: low (82.6%), intermediate (7.7%), childhood-limited (5.8%) and persistent (3.9%). ADHD PRS were higher in the persistent compared to each of the other 3 52 trajectories (χ2(1)=4.70-14.67, p<0.001-0.03, OR=1.22-1.31). Findings were specific to ADHD PRS; other psychiatric PRS did not differ across trajectories. Multi-morbidity was also highest in the persistent trajectory (χ2(1)= 31.16-136.85, p<0.001, OR=1.90-6.83) and was associated with persistence independent of PRS. Conclusions and Relevance. ADHD symptom persistence across childhood/adolescence in the general population is associated with higher ADHD PRS. Childhood multi-morbidity was also associated with persistence and may help to identify children with ADHD whose symptoms are most likely to continue into adolescence.
Original languageEnglish
Pages (from-to)1285-1292
Number of pages8
JournalJAMA Psychiatry
Volume73
Issue number12
Early online date2 Nov 2016
DOIs
Publication statusPublished - Dec 2016

Keywords

  • ALSPAC
  • ADHD
  • trajectories
  • polygenic risk scores
  • genetic
  • multimorbidity
  • longitudinal

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  • MRC UoB UNITE Unit - Programme 1

    Davey Smith, G.

    1/06/1331/03/18

    Project: Research

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