Schizophrenia and rheumatoid arthritis don't seem to have a lot in common, aside from being often debilitating conditions that each affect around 1 percent of the population. One is a psychiatric disorder and the other an auto-immune condition, but new research has confirmed there is a genetic trade-off between the two, with gene variations that make people more susceptible to one reducing the risk of the other. The work has identified eight genes that appear to play a role in this biological see-saw, providing opportunities to learn about both conditions.
We know that environmental conditions partially determine whether someone will suffer the confusion and false perceptions associated with schizophrenia or the joint pain caused by the body's immune system's attack on its own cells that defines rheumatoid arthritis. Nevertheless, both also run in families and are known to have a strong genetic component, estimated at 70 percent for schizophrenia.
“Several previous research studies have hinted at a potential inverse relationship in the prevalence and risk for the two disorders, so we wondered if individual genetic variants may exist that could have opposing effects on the risk of schizophrenia and rheumatoid arthritis,” said Professor Vishwajit Nimgaonkar of the University of Pittsburgh. The genetics of both diseases have been fairly well studied, so there was plenty of data for Nimgoankar and his colleagues to work with.
After searching through existing databases of alleles (gene variations), Nimgaonkar and colleagues found 18 that appear to raise the risk of one of schizophrenia or rheumatoid arthritis while lowering the other. All involved the change of one genetic “letter” of the most common form of eight genes from the section of our genome known to be control the functioning of the immune system.
In npj Schizophrenia, Nimgaonkar reports that two of these genes, HLA-B and HLA-C, encode proteins that appear in both the brain and cells of the immune system. It appears certain single nucleotide polymorphisms (SNPs) alter the production of proteins to improve the functioning of one aspect of the body at the expense of another, providing a level of protection against one disease while increasing risk for the other.
The HLA region has been thought to be related to both diseases for more than 40 years. Besides providing confirmation for these suspicions, Nimgaonkar's work will help future studies home in on the most relevant parts of our DNA.
Interventions that raise the risk of one condition while treating the other may be something of a devil's bargain, but it may be possible to tailor treatment to consider which condition poses more risk to an individual. Meanwhile, we have confirmation the immune system plays a role in schizophrenia, and a demonstration of the benefit of scientists looking outside their specialization.