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Title: Exploring the aetiology of ADHD : rater effects, co-occurring traits and polygenic scores
Author: Merwood, Andrew
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2013
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The precise aetiology of attention-deficit/hyperactivity disorder (ADHD) and its association with co-occurring traits remains unclear. Accordingly, the overarching aim of this thesis was to address several ambiguities surrounding the causes and correlates of ADHD. The first of these ambiguities concerns rater effects in twin studies. This was addressed by examining parent, teacher and child self-ratings of ADHD symptoms obtained concurrently using population-based twin data. Results revealed significantly lower heritability for self-ratings than for parent or teacher ratings of ADHD symptoms, but also identified a common genetic basis for the different informant ratings of ADHDrelated behaviours. The second of these ambiguities concerns the association between ADHD and Cloninger’s dimensions of temperament, examined in a population-based sample of adult twins. Results revealed heterogeneity in the phenotypic and aetiological associations of hyperactivity-impulsivity and inattention with the different dimensions of temperament. The third of these ambiguities concerns the relationship between ADHD and emotional lability. This was initially addressed in a twin study of children and adolescents. Results revealed significant phenotypic associations and a common genetic basis for symptoms of hyperactivity-impulsivity, inattention and emotional lability. A second study examined the association of the same symptom dimensions with measures of cognitive performance in child twin pairs. Phenotypic and genetic analyses indicated no direct association between cognitive performance and emotional lability after controlling for the symptoms of ADHD. The fourth of these ambiguities concerns the disparity between quantitative and molecular genetic studies of ADHD. This was addressed by testing the polygenic theory of ADHD. A polygenic profile score was generated using genome-wide association results derived from a large discovery sample of ADHD cases and controls. The profile score was significantly associated with ADHD affection status and with ADHD symptom scores in independent samples. The implications of these findings and future directions for research are discussed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available