According to a recent Yale study, many common psychiatric disorders might be genetically linked to a variety of immune disorders.
Researchers at the Yale School of Public Health studied the genetic phenomenon pleiotropy — when one gene affects more than one phenotype — between five psychiatric disorders and seven immune disorders. After pairing the psychiatric disorders, including schizophrenia and depression, with immune disorders, such as rheumatoid arthritis and Crohn’s disease, researchers found a correlation between 24 of the 35 psychiatric-immune disorder pairs. The reason for this correlation, said study senior author Hongyu Zhao, was that some regions on the genome sequence code for both psychiatric and immune disorders, suggesting a possible relationship between the two.
“Perhaps the inspiration for the study was that this has been a question for decades and we were able to confirm that the major histocompatibility locus on the genome contributes to both immune and psychiatric disorders, establishing the possibility of a correlation,” said the study’s first author Qian Wang GRD ’18, who studies computational biology and bioinformatics.
According to Zhao, who is also a professor of public health biostatistics and genetics at the Yale School of Public Health, the research was made possible by the abundance of data based on recent genomic findings. For instance, knowing the 118 locations of schizophrenia genes on the genome makes it possible to compare if the same location codes for an immune disorder, Zhao said. Using that information, researchers found a positive correlation between genetic variants that, for example, simultaneously code for a higher risk of schizophrenia and a higher risk of Crohn’s disease or coded for prevention of both disorders, indicating a same-effect direction.
The researchers obtained their data, which consisted of genomes showing genetic variants, from public websites and analyzed the genome using a model designed in their own lab.
“It’s important that we could resolve the nature between the genetic pleiotropy in these cases because pleiotropy was just a phenomenon, and the GPA model [we used] could locate and pinpoint specific points of its existence,” Wang said.
Margit Burmeister, professor in the University of Michigan Departments of Human Genetics and Psychiatry, who was not involved in the study, said its findings, while exciting, may not prove a positive correlation between psychiatric and immune disorders. She said a recent study actually found a negative association between the genetic variants that code for risk factors of psychiatric and immune disorders, contradicting the Yale study. This other paper states that the same genetic variants that are increasing risk for rheumatoid arthritis are actually decreasing risk for schizophrenia.
“The most important fact is there is genetic causative overlap between immune system and schizophrenia,” said Burmeister.
However, she included that, in light of the recent study that proved a negative correlation, the Yale study should have included a comparison to other kinds of major diseases like diabetes to show that having a genetic overlap between the psychiatric and immune diseases is actually unique.
In comparison to previous research in pleiotropy, Yale’s study was the first systematic genome study. The researchers used the entire genome sequence instead of just looking at chunks or half of the genome, Zhao said. This made the study more global and unbiased, Zhao added.
The research’s implications establish that immune functions may play a role in psychiatric disorders, said Wang, adding that other researchers can use this information to work on preventing the occurrence of genes that increase the risk of psychiatric and immune disorders.
Each year, nearly one in five Americans experience some sort of mental illness, according to the Substance Abuse and Mental Health Services Administration.