Oral Presentation 9th GeneMappers Conference 2012

Evaluating genome-wide methylation differences in monozygotic twins discordant for Major Depressive Disorder (#22)

Enda M Byrne 1 , Tania Carillo Roa 2 , Grant W Montgomery 3 , Lutz Krause 3 , Nicholas G Martin 3 , Naomi R Wray 1
  1. Queensland Brain Institute, St.Lucia, QLD, Australia
  2. University of Queensland, St.Lucia, QLD, Australia
  3. Queensland Institute of Medical Research, Brisbane, QLD, Australia

There is increasing recognition of the potential importance of epigenetic changes in the development of psychiatric disorders. Major Depressive Disorder is a common complex disorder, with an estimated heritability of 40%, indicating that a substantial proportion of the variance in risk is due to individual differences not encoded in the DNA sequence. Monozygotic twin pairs discordant for the disease of interest represent a powerful design in epigenetic studies. 

Six male MZ pairs and six female MZ pairs that were discordant for MDD were selected for inclusion, and a matched set of six male MZ pairs and six female MZ pairs that were concordant for not having MDD and low neuroticism were selected as the control pairs. Each concordant MZT pair was selected to match as closely as possible to a discordant pair on a number of key environmental variables such as date of sample collection, smoking, alcohol and drug use. A total of 48 twins were included. Bisulphite conversions of previously extracted DNA from white blood cells were performed, and methylation patterns assessed using the Illumina HM 450 BeadChip array.

A linear model was used to test for differences in methylation between the sexes and between cases and controls. This analysis was performed for each probe and separately for groups of probes organised by their annotated region (e.g. island, shelf, shore). In addition, a test for differences in variation in methylation between cases and controls was performed. Results for the most significant differentially methylated sites, genes, and biological pathways will be presented.