A Genome Wide Association study of Unipolar Depression

Lead Research Organisation: King's College London
Department Name: Unlisted

Abstract

Depressive disorder is a very common condition that is substantially influenced by heredity. However genetic basis is complicated, involves an interplay with environmental stress and is , so far, not well understood at a molecular level. This study aims to identify genes involved in susceptibility to depression.It will have important implications for the future discovery of novel targets for new safer, more effective medications.

Technical Summary

We will carry out a genome wide association (GWA) study using a very large sample (N~4,700) of white European cases of well defined unipolar depression (minimum 2 severe episodes) and a set of ethnically matched super controls screened for lifelong mental health (N~2400). The samples to be genotyped comprise white European subjects collected by ourselves and colleagues - cases: 3,736 and screened ?super controls?: 1,500. In addition we will add GSK data already generated on 943 white German cases defined in exactly the same way as our own cases and 868 ethnically matched ?super controls?.
We will further examine our top 500 ?hits? against white European controls from the Wellcome Trust?s Case Control Consortium (N~3,000), a GSK control collection (N~4,000), and an Illumina control panel (N~10,000).
We will use the GSK comprehensive annotation of SNPs as well as information from recent linkage studies to select targets that merit further detailed investigation, including additional genotyping where indicated.
We will compare our findings with those from a GWA study currently underway in the US (N~1, 800 cases, 1, 800 controls) and subsequently will participate in a GWA combined/meta-analysis study consortium.
The study promises to identify novel loci involved in the aetiology of unipolar depression.

Publications

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Bilbao A (2008) Loss of the Ca2+/calmodulin-dependent protein kinase type IV in dopaminoceptive neurons enhances behavioral effects of cocaine. in Proceedings of the National Academy of Sciences of the United States of America

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Breen G (2008) Variable number tandem repeats as agents of functional regulation in the genome. in IEEE engineering in medicine and biology magazine : the quarterly magazine of the Engineering in Medicine & Biology Society

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Breen G (2010) Practical informatics approaches to microsatellite and variable number tandem repeat analysis. in Methods in molecular biology (Clifton, N.J.)

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Butler AW (2010) A genomewide linkage study on suicidality in major depressive disorder confirms evidence for linkage to 2p12. in American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics

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Butler AW (2010) Integrating phenotypic data for depression. in Journal of integrative bioinformatics

 
Description A Genome association study of Unipolar depression and Initial exploration of functional Allelic Variation
Amount £1,168,363 (GBP)
Funding ID G0701420 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start  
 
Description Work Package WP8 of NEWMEDS, European Commision Innovative Medicines Initiative
Amount £677,360 (GBP)
Organisation European Commission 
Sector Public
Country European Union (EU)
Start  
 
Title Opcrit+ 
Description Computerised psychiatric diagnostic system 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2009 
Provided To Others? Yes  
Impact Incorporated in South London & Maudsley NHS Trust's electronic medical records. 
 
Description Identical twins discordant for autism: epigenetic (DNA methylation) biomarkers of nonshared environmental influences 
Organisation Autistica
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution This grant will support the first epigenetic study of identical (monozygotic, MZ) twins discordant for the components of autistic spectrum disorder (ASD). ASD-discordant MZ twins will be selected from the PI's Twins Early Development Study (TEDS). DNA extracted from blood will assessed using NimbleGen NimbleChip Arrays containing probes spanning the promoter regions of all known genes in the genome. The goal is to identify epigenetic factors that make MZ twins discordant for ASD, that differ
Impact This collaborative multidisciplinary project is a good example of the added value of the Centre because few institutions would have the expertise in epigenetics (Jon Mill), quantitative genetics (Robert Plomin), molecular genetics (Leo Schalkwyk), ASD (Angelica Ronald), and statistical genetics and microarray analysis (Tom Price). This research also represents a major step in the Centre's goal to create a biological foundation for environmental research.
Start Year 2008
 
Description School visits to the Centre for an open day on Careers in Science 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact In conjunction with the Institute of Psychiatry, 60-80 GCSE level and sixth form school students attend a two day workshop hosted here at the MRC SGDP Centre. They met with a number of genetic psychiatrists, researchers, and a host of scientists from different psychiatric disciplines,and attended a variety of talks by IoP academics.

Encouraging students to pursue careers in science and psychology and psychiatry upon leaving school.
Year(s) Of Engagement Activity 2007,2008,2009,2010,2011,2012,2013
 
Description Visit by 28 16-18 year old school students to Institute of Psychiatry 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact 28 school students visited the IoP for 2 days, involving a variety of talks by IoP academics. Peter McGuffin gave a talk entitled "Mental illness: is it all in the genes?"

The talk took place on 19 November 2010
Year(s) Of Engagement Activity 2010