Abstract
The precise aetiology of attention-deficit/hyperactivity disorder (ADHD) and itsassociation 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.
| Date of Award | 2013 |
|---|---|
| Original language | English |
| Awarding Institution |
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