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.
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

Andreoli SB
(2009)
Violence and post-traumatic stress disorder in Sao Paulo and Rio de Janeiro, Brazil: the protocol for an epidemiological and genetic survey.
in BMC psychiatry

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

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

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

Breen G
(2011)
A genome-wide significant linkage for severe depression on chromosome 3: the depression network study.
in The American journal of psychiatry


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

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

Campos-De-Sousa S
(2010)
Nuclear receptor rev-erb-{alpha} circadian gene variants and lithium carbonate prophylaxis in bipolar affective disorder.
in Journal of biological rhythms

Cole JH
(2013)
Body mass index, but not FTO genotype or major depressive disorder, influences brain structure.
in Neuroscience
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 |