Aims:

1. Test for associations between prenatal exposures to adversity (toxins and diet) and ADHD (age 7/8) traits.

2. Test for associations between germline genetic variation (identified in large scale case control genetic discovery studies of ADHD diagnosis) and ADHD (age 7/8 traits).

3. Identify epigenetic signatures at birth associated with ADHD.

4. Test if epigenetic signatures index/mediate link between prenatal exposures, genes and ADHD.

5. Use epigenetic signatures to form hypotheses about relevant environmental exposures for ADHD.

6. Identify those at high ADHD risk (those at high genetic/prenatal environmental/epigenetic risk at birth).

7. Identify preschool enrichment factors (diet, care) that modify early ADHD risk.

Hypotheses

1. Genetic risks and prenatal exposure to environmental hazards that are indexed by epigenetic signatures alter brain development and increase ADHD risk (at age 7) .

2.Epigenetic and genomic signatures provide clues on biological and environmental risks that might be future targets for early intervention.

3. Birth risks (captured by germline genetic risks, prenatal environment and epigenetic profile) on ADHD are modifiable by postnatal enrichment.

Exposures

1.Foetal exposure to lead, mercury, other toxins (atrazine available, PCBs to be assayed), maternal cigarette smoking (reported and cotinine levels), alcohol

2.Maternal diet and dietary supplementation

3. Child germline genetic variation-composite of common and rare variants known to be associated with ADHD (via GWAS then exome sequencing).

4. Epigenetic array data from ARIES at birth -cord blood (additional epigenetic micrarray data to be obtained on ADHD cases in ALSPAC who are not in ARIES-this will be costed in)

Outcomes

1. Trait ADHD aged 7/8 asssesed by DAWBA

Modifiers

1. Child diet

2. Early maternal care

Confounders

1. Sex of child

2. Social class

3. IQ

4. Comorbid conduct/mood problems.