This proposal is an extension of our proposal previously accepted by the ALSPAC executive committee (B627). The proposal (B627) was approved to investigate genetic mechanisms that may potentially explain the association between cardiovascular disease risk factors and psychosocial outcomes (specifically aggressive behaviour and anxious/depressed symptoms) throughout childhood. The association between CVD and its risk factors and psychosocial outcomes has been well documented in adult studies and more recently in childhood studies. There are no studies that have been published that have investigated genetic mechanisms that may explain this association.

In this proposal we seek approval for use of candidate genes, specifically Leptin (LEP), its receptor (LEPR) and Monoamine Oxidase A (MAO-A) gene, available within the ALSPAC genome wide scan genotype data.

We will use these SNPs to replicate our findings within the Western Australian Pregnancy Cohort (Raine) Study, an ongoing longitudinal prospective birth cohort of children. Briefly, the original cohort consisted of 2,900 pregnant women, all of whom were recruited at approximately 18 weeks of gestation. Their babies were serially followed from recruitment at the average ages of one, two, three, six, eight, ten and fourteen, seventeen and currently twenty-one years. The majority of the children are of Caucasian ethnicity (82% have two Caucasian parents). Depression and Aggression measures and certain CVD risk factors were assessed from the ages of five onwards.

Analysis of the ALSPAC data (genotype and phenotype) will be carried out inBristol. As we have most of the phenotype data, Sandra Louise will be able to provide all the necessary syntax required to carry out the genetic analysis.