Genome-wide studies of the genomes across the human population have shown a range.
However, it has been difficult to tease apart the role of common variants in these genetic differences.
The study of genome-wide variation in clinical disorders such as schizophrenia, obesity and autism raises new questions.
The team at the University of Cambridge has now tackled these problems by combining the genetic analyses of a large number of people with different types of schizophrenia.
“We used a database of more than 6,500 patients to assess the contribution of common genetic variants in the disease, and found that almost half the patients have some variant of the ‘crispsons disease’ variant that encodes a peptide that we think is involved in this disorder,” says Professor Colin Burch of the Centre for Neuropsychopharmacology at the university’s Institute of Neurology.
The researchers identified three different variants in this variant in about 5% of patients.
“Our results show that the variants are all linked, and we can rule out any association between this variant and schizophrenia.”
The first variant in the group is found at the 5′ position of the human genome, and is called a C5H19 gene variant.
The second is found on chromosome 17.
The third is located in the 6′ position on chromosome 9.
It is associated with schizophrenia in patients with the schizophrenia variant, and in patients without the variant.
These variants have been identified in a range a few hundred in the human species, and most of them are thought to have been fixed before the human disease appeared.
“There are still hundreds of thousands of variants in human genomes, and there are many that are not associated with disease.
But the fact that most of these variants are not related to schizophrenia suggests that they are important,” says Prof Burch.
The human variant, C5HK1, encodes the dopamine receptor and is involved with reward processing.
This variant is linked to schizophrenia in about one in every 10 patients, and the researchers found that it was present in about 50% of cases of schizophrenia, and about one-third of those without the schizophrenia variants.
The other variants were found in more than half of patients without schizophrenia.
The new study highlights the fact, however, that many of these different variants are associated with different disease processes.
“This means that we need to look at the impact of the variants in different diseases in order to understand what they do,” Prof Bunch says.
This is not the first time that researchers have found variants linked to specific diseases.
Earlier studies in the Human Genetics Database have found associations between variants in genes related to obesity and metabolic syndrome, and variants linked with depression and schizophrenia in people with both disorders.
“When we look at what is known about the common variants, we find a lot of overlap,” says Dr Robert Alder of the National Institute for Health Research, UK.
The authors hope to continue to work on the genetic basis of schizophrenia in future, by studying the genomes and the genomes’ structure, so that we can determine how genes are connected to disease.
“It will be interesting to see how the human variant C5K1 affects patients with schizophrenia.
In general, it’s been shown that there is some correlation between the risk of developing schizophrenia and the severity of the disease.
We don’t know how this would change if we were able to isolate a single variant from schizophrenia,” says study co-author Dr Anna-Maria Zuardi from the University Medical Centre Groningen.
“However, we think it is important to look more closely at the genetic differences between schizophrenia patients and healthy controls in order see if they are responsible for this association.”
A report on the study appears in Nature Genetics.