Does immune dysfunction contribute to schizophrenia?

October 10, 2012

A new study reinforces the finding that a region of the genome involved in immune system function, called the major histocompatibility complex (MHC), is involved in the genetic susceptibility to schizophrenia.

Schizophrenia is among the most disabling . Approximately 80% of the risk for developing schizophrenia is heritable, but there has been slow progress in identifying that contributes to the risk for schizophrenia.

The current paper contributes to this growing literature by identifying variants of genes that influence the function of the immune system which may contribute to the heritable risk for schizophrenia.

Two large, international, collaborating groups of scientists – the Wellcome Trust Case Control Consortium 2 and the Irish Schizophrenia Genomics Consortium – conducted this new study.

They first performed what is called a discovery scan, where they analyzed over 6 million genetic variants in and controls from Ireland. This allowed them to compile a list of variants that showed the strongest association signals with schizophrenia.

They then performed similar work in an independent sample of 13,195 cases and 31,021 controls from around the world in order to search for the same top 'hits'. This wealth of data was provided by the international schizophrenia genetics community. This replication work is an important scientific strategy, particularly in the field of genetics, to strengthen and support the original findings.

Using these multiple datasets and approaches, their findings lend further support for the involvement of the in schizophrenia susceptibility. "In this large collaborative effort, we have replicated evidence for specific risk and protective alleles at the MHC locus - a critical step teasing apart the mechanisms involved," commented Dr. Aiden Corvin, one of the lead authors and a professor at Trinity College Dublin. "However, pinpointing specific risk genes or has been challenging because this is a region of great genomic variation within and between populations."

These genetic findings also highlight an important gap in our understanding of the biology of schizophrenia. There is a long history of interest in immunologic contribution to schizophrenia including wide ranging observations linking viral infection, gluten sensitivity, changes in cytokine levels in blood and cerebrospinal fluid, and other factors to schizophrenia.

"Despite this, we have relatively little understanding how alterations in immune function are involved in the etiology and pathophysiology of this disorder," commented Dr. John Krystal, Editor of Biological Psychiatry. "Immunologic studies in schizophrenia that illuminate the nature of the contribution of variation in immune system genes to schizophrenia will be an important new direction in schizophrenia research."

Explore further: Large study finds genetic 'overlap' between schizophrenia, bipolar disorder

More information: The article is "Genome-wide association study implicates HLA-C*01:02 as a risk factor at the MHC locus in schizophrenia" by Irish Schizophrenia Genomics Consortium & the Wellcome Trust Case Control Consortium 2 (doi: 10.1016/j.biopsych.2012.05.035). The article appears in Biological Psychiatry, Volume 72, Issue 8 (October 15, 2012).

Related Stories

Large study finds genetic 'overlap' between schizophrenia, bipolar disorder

September 21, 2011
Knowledge about the biological origin of diseases like schizophrenia, bipolar disorder and other psychiatric conditions is critical to improving diagnosis and treatment.

The brains of people with schizophrenia are on 'red alert', study finds

August 8, 2012
New Australian research shows that the brains of people with schizophrenia may be under attack by the immune system, providing the strongest evidence to date of a link between immune function and schizophrenia.

Recommended for you

Forgotten strands of DNA initiate the development of immune cells

September 21, 2017
Intricate human physiological features such as the immune system require exquisite formation and timing to develop properly. Genetic elements must be activated at just the right moment, across vast distances of genomic space.

Genome editing reveals role of gene important for human embryo development

September 20, 2017
Researchers have used genome editing technology to reveal the role of a key gene in human embryos in the first few days of development. This is the first time that genome editing has been used to study gene function in human ...

A piece of the puzzle: Eight autism-related mutations in one gene

September 19, 2017
Scientists have identified a hotspot for autism-related mutations in a single gene.

Scientists identify key regulator of male fertility

September 19, 2017
When it comes to male reproductive fertility, timing is everything. Now scientists are finding new details on how disruption of this timing may contribute to male infertility or congenital illness.

New assay leads to step toward gene therapy for deaf patients

September 18, 2017
Scientists at Oregon State University have taken an important step toward gene therapy for deaf patients by developing a way to better study a large protein essential for hearing and finding a truncated version of it.

A new approach to high insulin levels

September 18, 2017
Diabetes is characterised by a deficiency of insulin. Its opposite is a condition called congenital hyperinsulinism—patients produce the hormone too frequently and in excessive quantities, even if they haven't eaten any ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.