Conduct problems (CP) in youth affect society in a wide and penetrating manner; the victimization and distress to individuals and impairment of life opportunities is substantial. The associated costs are thought to be especially severe for youth with an early onset (at or before the age of 10 years) of CP - these youth are often raised in high-risk environments (family, community); show abnormal neurocognitive development; and are at risk for a persistent pattern of offending (1-3).

Previous studies highlight that a poor diet (e.g., consumption of energy-dense foods that are high in saturated fat and low in unsaturated fat) in early life (i.e., in prenatal and early postnatal periods) can disturb child neurodevelopment and lead to cognitive, emotional and behavioural problems in later life (4-13). To date, however, no existing research has integrated - in a developmental context - nutrition (i.e., quantity and quality of dietary fat) and biological markers (genetic, epigenetic and metabolic) that can help to identify the mechanisms underlying the associations between poor nutrition from prenatal period through childhood and CP. For example, although epigenetic modifications have been associated with poor nutrition in general (14), further research is needed to examining the this is related to early onset of CP - and also the degree to which functional variation within genes that are involved in metabolism of the key macronutrients might moderate the associations between nutrition and DNA methylation in relation to CP (15, 16).

This application proposes a systematic examination of the impact of prenatal and postnatal nutrition and environmental risk exposure on CP in The Avon Longitudinal Study of Parents and Children (ALSPAC; UK). The developmental phenotype of CP trajectories between ages 4 and 13 years is available for the ALSPAC children (2). The sub-sample of ALSPAC children includes extensive measures of diet macronutrients using Food Frequency Questionnaire and dietary diary, and nutrition biomarkers available from a prenatal period through late-childhood; as well as whole-genome data for mothers and children; and DNA methylation status data available for children at birth, at ages 7 and 15-17 years.

The project aims to address the following research questions:

Aim 1: Does prenatal and/or early postnatal nutrition affect CP developmental trajectories?

Sub Aim 1a: Are these associations mediated by earlier neuro-cognitive development?

Sub Aim 1b: Are these associations affected by child stress exposures?

Aim 2: Are associations between nutrition and CP (partially) explained by DNA methylation?

Sub Aim 2: Are these associations moderated by child stress exposures?

Aim 3: Examine the role of SNPs involved in the metabolic pathways of key nutrients.

Aim 4: Examine causal associations using Mendelian Epigenetic Randomization.