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Shared Genetic Influences Between Attention-Deficit/Hyperactivity Disorder (ADHD) Traits in Children and Clinical ADHD

https://doi.org/10.1016/j.jaac.2015.01.010Get rights and content
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Objective

Twin studies and genome-wide complex trait analysis (GCTA) are not in agreement regarding heritability estimates for behavioral traits in children from the general population. This has sparked a debate on the possible difference in genetic architecture between behavioral traits and psychiatric disorders. In this study, we test whether polygenic risk scores associated with variation in attention-deficit/hyperactivity disorder (ADHD) trait levels in children from the general population predict ADHD diagnostic status and severity in an independent clinical sample.

Method

Single nucleotide polymorphisms (SNPs) with p < .5 from a genome-wide association study of ADHD traits in 4,546 children (mean age, 7 years 7 months) from the Avon Longitudinal Study of Parents and Children (ALSPAC; general population sample) were selected to calculate polygenic risk scores in 508 children with an ADHD diagnosis (independent clinical sample) and 5,081 control participants. Polygenic scores were tested for association with case-control status and severity of disorder in the clinical sample.

Results

Increased polygenic score for ADHD traits predicted ADHD case-control status (odds ratio = 1.17 [95% CI = 1.08–1.28], p = .0003), higher ADHD symptom severity (β = 0.29 [95% CI = 0.04–0.54], p = 0.02), and symptom domain severity in the clinical sample.

Conclusion

This study highlights the relevance of additive genetic variance in ADHD, and provides evidence that shared genetic factors contribute to both behavioral traits in the general population and psychiatric disorders at least in the case of ADHD.

Key Words

attention-deficit/hyperactivity disorder (ADHD)
polygenic risk scores
Avon Longitudinal Study of Parents and Children (ALSPAC)
common variants
genetics

Cited by (0)

This article is discussed in an editorial by Dr. Philip Asherson and Dr. Maciej Trzaskowski on page 249.

Clinical guidance is available at the end of this article.

The MRC IEU is supported by the Medical Research Council and the University of Bristol (grant code MC_UU_12013/1-9), and the MRC Centre for Neuropsychiatric Genetics and Genomics is supported by the Medical Research Council, the Wellcome Trust, and Cardiff University (grant code 079711/Z/06/Z). The UK Medical Research Council, the Wellcome Trust (grant ref: 102215/2/13/2), and the University of Bristol provide core support for Avon Longitudinal Study of Parents and Children (ALSPAC). ALSPAC genome-wide association study (GWAS) data was generated by Sample Logistics and Genotyping Facilities at the Wellcome Trust Sanger Institute and LabCorp (Laboratory Corporation of America), supported by 23andMe.

Dr. Stergiakouli served as the statistical expert for this research.

Disclosure: Drs. Stergiakouli, Hamshere, Langley, Evans, St Pourcain, Timpson, Profs. Owen, O’Donovan, Thapar, and Davey Smith, and Mrs. Martin report no biomedical financial interests or potential conflicts of interest.