In a recent study published in the Annals of Human Genetics, a team of researchers from the UCL Genetics Institute highlighted the role of genes involved in obesity and schizophrenia. The study findings could lead to a better understanding of the DNA variants affecting the risk of these disorders and encourage the development of new prevention and treatment strategies.
In the study, which was part of the Wellcome Trust-funded UK10K research project, the team of researchers conducted a gene sequence analysis of more than 1 million genetic variants in over 2,000 participants who had either schizophrenia or severe childhood onset obesity. The study results identified the genes variants that more frequently occurred in either the obese or the schizophrenic participants.
Lead researcher Professor David Curtis said: “Schizophrenia and obesity represent huge public health problems. Both conditions have a substantial genetic contribution which is at present poorly understood. This study illustrates the way that genetic sequencing technology can help us to make progress in this area.”
Two genetic variants in the MC4R gene that are known to be protective against the development of obesity were rarely observed in the obese study participants. However, rare variants in the genes CRHR1 and SNORD115 were more commonly observed in the participants with obesity, indicating that if there is dysfunction in these genes, there is an increased risk for the development of obesity.
Moreover, SNORD115 lies in a chromosome 15 region that is deleted in Prader-Willi syndrome, a disorder that results in intense food cravings. The study findings indicate that SNORD115 may lead to this condition. The CRHR1 and SNORD115 genes have been found to be involved in metabolic functions, however, this study was the first to suggest that they are implicated in the risk of developing obesity.
The results of the study entitled “Practical Experience of the Application of a Weighted Burden Test to Whole Exome Sequence Data for Obesity and Schizophrenia” also specifically showed that participants with schizophrenia had an increase in the frequency in the NLGN2 variants, a gene that is involved in regulating synapses. The findings provide more evidence concerning schizophrenia as a condition that is in part related to synaptic dysfunction. Further studies are planned to look at other genes also identified in this study.
“Genetic research is entering an exciting period,” said Professor Curtis. “We are now able to study directly the changes in DNA sequence which alter the code of specific genes, rather than simply studying genetic markers which lie close to genes. This will allow us to understand exactly how changes in this sequence can change the function of molecules in the cell and how this can go on to influence the risk of developing serious diseases. In time, this will lead to improved methods of prevention and treatment and we will be able to give patients a better understanding of the causes of their conditions.
“Genetic sequencing identifies millions of tiny variants in the genetic code between one person and another,” he added. “Because there are so many variants, it can be difficult to be sure which ones contribute to disease risk. However, as we obtain sequence data for more and more people, we will gradually develop a fuller understanding of the consequences of these variants. For example, we can study the effects of specific DNA variants in cells cultured in the lab and using model systems like this, we can test new drugs to try to correct the problems caused.”
Dr. Richard Durbin, at the Wellcome Trust Sanger Institute, said: “The UK10K collaborative research project has involved researchers across Britain who sequenced all the genes in nearly ten thousand British people with a variety of medical conditions. We are delighted that it has enabled a wide range of genetics studies, including these important findings on the genetics of schizophrenia and obesity.”
