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Neuropsychiatric Genetics Research Group
Attention-Deficit/Hyperactivity Disorder

International Multi-centre ADHD Genetics Project

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Many families with a child with ADHD have met with researchers from Trinity College Dublin and contributed to research into ADHD. The IMAGE study has been run in 11 centres in Europe, as well the Department of Psychiatry, TCD. It is funded by the National Institute of Mental Health in the USA. The aim is to collect blood samples from 1400 families where there is a child with ADHD. Blood samples are sent to the USA, where they are preserved for research into ADHD and genetics. At Trinity College Dublin, we have taken an active role in the analysis of both the clinical and genetics data coming from this collaboration.
From a clinical perspective, at Trinity College Dublin we have focused on examining the clinical co-morbidity in ADHD, including the presence of conduct, oppositional disorders and autism-traits (Mulligan, Anney, et al., 2008). These data and others are being examined within the various genetic resources that have been generated on this cohort.

There are five major genetic datasets based on the IMAGE consortia collections;

  1. Study 1: Candidate Gene Study on approximately (~1000 DNA Markers)
  2. Study 2: CIDR Linkage Study (~6000 Markers)
  3. Study 3: CIDR Linkage Study Follow-Up (~6000 Markers)
  4. Study 4: GAIN Perlegen Genome-Wide Association Study (GWAS) (~600,000 Markers [Perlegen Array])
  5. Study 5: IMAGE-II GWAS Follow-Up (~500,000 Markers [Affymetrix Array]) – (complete mid-2009)

The IMAGE consortium initially examined individuals from this study with a selection of hypothesis-defined DNA markers in 51 candidate genes (Study 1) implicated in ADHD (Brookes, Xu, Chen et al., 2006). This was followed by specific follow-up of interesting findings around the dopamine transporter gene (SLC6A3) (Brookes, Xu, Anney.,et al 2008), and the inheritance of risk DNA from mothers and fathers (Anney, Hawi, Sheehan, et al., 2008).. We continued this analysis using the hypothesis-free linkage approach, identifying regions of interest on chromosome 1, 9 and 16 (Zhou, Asherson, Sham., et al 2008; Asherson, Zhou, Anney., et al 2008).

In 2007, we were awarded a GAIN project, which enabled this sample to be examined using a new technology that looks at many hundreds of thousands of DNA markers across the genome. This study is important as so many families and so many markers can be studied together in one group. This will ultimately enable us to better identify genes and variation that offer risk or protection against developing ADHD or aspects of ADHD.

Study 4, the GAIN GWAS was the first published GWAS of ADHD (Neale, Lasky-Su, Anney et al., 2008). Additional research manuscripts have followed from this data looking at symptom severity (Lasky-Su, Neale, Franke, et al., 2008), age-of-onset (Lasky-Su, Anney, Neale, et al., 2008), and co-morbid disorders such as conduct disorder and autism-traits (Anney, Lasky-Su, O'Dúshláine, et al., 2008).

We are entering Study 5, where we can further examine the association signals identified through our previous research in large independent samples including the IMAGE-II project. Moreover, we have joined the ADHD component of the Psychiatric Genetics Consortium – the largest single global collaboration of psychiatric geneticists. The PGC is set with the task to bring together data from 47 studies, including whole genome data of over 500,000 markers on over 80,000 individuals. These data will undergo sophisticated statistical analysis to understand within and across disorder genetic risk.

Many thanks to all the families who have given samples the IMAGE study, without whose contribution this work could not take place. Your time and effort are much appreciated. We have been invited to present aspects of these data at many prestigious local and international meetings on genetics and psychiatry including the World Congress on Psychiatric Genetics, the American Society of Human Genetics, the ADHD Genetics Network, the Irish Society of Human Genetics and the Irish College of Psychiatrists.

For further information

Dr Aisling Mulligan

Last updated 21 September 2016 by School Web Administrator.