A whole genome association study of unipolar depression

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

Abstract

Depression is a very common disorder and is a major public health problem in the UK and throughout the world. There is good evidence from studies looking at families and twins that there is a substantial genetic contribution to depression, particularly recurrent disorder. Almost certainly the genetic component of depression results from many genes of small effect and there is also a complicated interplay with environmental factors such as distressing events. As yet we know little about which genes are involved in depression and the study aims to find at least to some of them. We will utilise a new technology that enables a search throughout the genome using approximately half a million markers. Finding genes involved in depression has great potential benefits for clinical practice, first in better understanding the biology of depression and thereafter in discovering better, safer medications.

Technical Summary

We will perform a two stage whole genome scan using the new Affymetrix 500K chip with a DNA pooling on pools stratified by sex.A subset will also be stratifed by presence or absence of adversity. SNPs identified by pooling experiments in both (DeCC and GENESiS) samples will be followed up by individual genotyping.
The samples that will be used have both been funded by previous MRC grants:
1. the Depression case-control ( DeCC)study consisting of over 1500 cases of recurrent clinical depressive disorder and 1500 controls screened for absence of psychiatric illness.
2. subjects from the population based GENESiS study who fall within the top 10% (N. = 570) and the bottom 10% (N. = 595) on a composite index designed to detect depressive and anxiety symptoms.

Publications

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Cohen-Woods S (2009) From age correction to genome-wide association. in Acta psychiatrica Scandinavica

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Gaysina D (2008) No association with the 5,10-methylenetetrahydrofolate reductase gene and major depressive disorder: results of the depression case control (DeCC) study and a meta-analysis. in American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics

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Green EK (2009) P2RX7: A bipolar and unipolar disorder candidate susceptibility gene? in American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics

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Schosser A (2010) NRG1 gene in recurrent major depression: no association in a large-scale case-control association study. in American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics

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Schosser A (2011) A follow-up case-control association study of tractable (druggable) genes in recurrent major depression. in American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics

 
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 A genome wide association study of unipolar depression
Amount £1,178,240 (GBP)
Funding ID G0701420 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 01/2008 
End 01/2010
 
Description Karen Ashwood Student Maintenance Grant
Amount £65,195 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
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 Gresham College Lecture, London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact A large audience attended a lecture entitled "Is it all in the genes?" There were questions and discussion after the talk.

Audience members registered interest in the study of the interplay of genes with environmental effects, and in research findings on the role of genes in response to treatment of mental disorders.
Year(s) Of Engagement Activity 2009