Its not often that Nature magazine publishes a triple-back-to-back-to-back, so take note if you’re interested in the genetics of mental illness. The 3 papers – [doi:10.1038/nature08185] involving 3,322 individuals with schizophrenia and 3,587 controls, [doi:10.1038/nature08186] 4,999 cases and 15,555 controls and [doi:10.1038/nature08192] 8,008 cases and 19,077 controls – are as massive and powerful as any genome-wide effort to-date. The results? Overall a common result showing linkage to the major histocompatibility complex or so-called ‘MHC genes’ located on chromosome 6. What to these genes do? and what’s the relevence to mental illness?
Here’s a quickie immunology primer on the biological function of the major histocompatibility genes. They encode proteins whose molecular function is display short peptides on the surface of aptly named antigen presenting cells in the immune system (think of your hand as an MHC protein holding onto an apple (the short peptide) and holding it out or presenting it to someone (an Helper T-Cell). This act of “presentation” is done so that the Helper T-Cells can determine whether such peptides are “self” or “non-self”. If such displayed peptides are non-self (such as a virus, endotoxin or bacterium), then the helper T-Cells will sound the alarm and initiate a T- or B-Cell based immune response aimed specifically at the offending invader. The movies below show the MHC proteins in their place displaying antigen peptides on the cell surface for binding with a helper T-Cell.
So, what does this have to do with mental illness? Although there are other non-immunological genes interspersed among the MHC genes, there is good reason to begin to explore the role of external infection and early development. The authors of one paper note that, “Schizophrenia patients are more likely, compared to the general population, to have been born in the winter or the spring. Although infections such as influenza and measles have been proposed as a possible mechanism for this distortion, a clear association between infectious agents and schizophrenia has not been demonstrated.”
The more we know, the more we don’t know. Hopefully more early environment data will be analyzed.