- A research team
from RIKEN Brain Science Institute have identified gene variations in the
risk for schizophrenia
- Detailed list of
splicing quantitative trait loci have been developed for schizophrenia
- Such genetic
variation studies can be used to identify the risk for other neurological
of DNA that are associated with alterations in gene expression which lead to
schizophrenia have been identified in a new study published in the Journal Nature Communications
. The alternate
splicing mechanism is affected by the implicated loci which results in the
development of schizophrenia
The study promises to unearth
various genes associated with the development of neurological conditions.
is a complex and prevalent mechanism which allows a single gene to be involved
in the production of varied proteins. Any dysregulation of this mechanism can
result in the development of many diseases. sQTLs or splicing quantitative
trait loci are genetic variants which control the process of alternative
splicing, though the mechanism in the brain has not been fully understood.
‘Gene variations identified in schizophrenia will aid in early identification’
A research team from the RIKEN Brain
Science Institute (BSI) and Yokohama City University (Japan) has put together a
detailed list of sQTLs present in the brain tissue of humans and have
identified that these variants were enriched among genomic regions that are
associated with neurological diseases like schizophrenia.
Atsushi Takata, who is the lead author of the study, and colleagues, studied
the RNA sequencing data obtained from samples of brain tissue of over 200 study
participants without any known psychiatric illness. The scientists found
- Numerous single
nucleotide polymorphisms (SNPs) are common variants of genes with possible
associations with the synthesis of RNA and alternative splicing. Such SNPs
are termed sQTLs.
scientists involved in the study believe that these sQTLs will aid in
understanding the framework of genes in the development of psychiatric
study, on further analysis of the interactions of these sQTLs with known
genetic regulatory elements, aided in identifying
- Patterns of
significant depletion or enrichment of specific sites that are involved in
binding histone or transcription factors.
genome-wide association studies that aided in identifying loci associated
with schizophrenia were also found to be enriched for sQTLs; this was
especially true for non-exonic sQTLs.
findings of the study aided in proving that such neurological conditions may be
caused due to changes in the splicing rather than due to alterations in the
genes that affect the gene to protein expression pathway.
studies have shown that methylation QTLs (mQTL) and expression QTL (eQTL) were
associated with an increase in schizophrenia risk. The current study, according
to Dr. Tadafumi Kato, who is the senior author of the study, aided in
determining that sQTLs were also associated with increased schizophrenia risk.
Disease Susceptibility Genes
scientists analyzed the part of the genome that overrepresented the sQTLs and
were able to locate four disease susceptibility genes which were found to be
implicated in schizophrenia. The genes were
were associated with the development of the nervous system, programmed cell
death or apoptosis and neurotransmission. An increase in sQTLs at loci that is
associated with schizophrenia is an indication that these genetic variations
are linked to schizophrenia risk. However, the scientists caution that the
genetic framework is extensive and the disease is very complex to be solely
defined by any particular genetic polymorphism.
is a psychiatric disorder.
- It has a lifetime
prevalence of 4.0 per 1,000
- It has a
morbidity risk of 7.2 per 1,000
- It occurs during
early adulthood or adolescence
- The development
of schizophrenia in the fifties is very rare
- Prevalence is
similar among males and females.
neurological disorder is characterized by fluctuating patterns and cognitive
disability. Its characteristic symptom is psychosis, along with hallucinations
The affected individual may also exhibit disorientation, emotional upheaval,
speech irregularity and severe mood symptoms that range from mania to
genetics of Schizophrenia is very complex with many genes associated with this
condition. Genome wide interaction studies are necessary to identify genes as
well as interactions between genes and the environment in the development of
is a combination of rare as well as commonly found mutations that lead to the
development of schizophrenia. It is important to identify these mutations as it
would aid in early identification of the disease, even before the onset of
symptoms. This would also aid in reducing or preventing psychotic symptoms that
are often associated with schizophrenia.
- The Role of Genetics in the Etiology of
Schizophrenia - (https:www.ncbi.nlm.nih.gov/pmc/articles/PMC2826121/)