Researchers at Weill Cornell Medicine – Qatar (WCM-Q) have recently examined the relationship between natural modifications of human chromosomes, a process called DNA methylation, and their effects on proteins circulating in the blood stream, shedding new light on the causes behind several common disorders.

Their findings may eventually help better understand complex diseases that involve chronic inflammation, including cardiovascular disease, obesity and rheumatoid arthritis.

The team of researchers, led by Dr Karsten Suhre, Professor of Physiology and Biophysics at WCM-Q, analysed data derived from blood samples of more than 1,300 individuals from Europe, Asia and the Middle East. The researchers examined how DNA methylation regulates important genes by looking at the proteins that these genes produce.

Methylation is a process by which a gene is turned on or off – i.e. methylation of a gene determines whether it creates a specific protein or not. This process often changes in response to disease or other stress factors acting on the human body, and DNA methylation can therefore inform researchers about which genes are affected by a certain disease.

DNA methylation
Representation of a DNA molecule that is methylated. The two white spheres represent methyl groups. They are bound to two cytosine nucleotide molecules that make up the DNA sequence. (Wikipedia)

By examining 450,000 methylation sites on all human chromosomes and measuring at the same time 1,100 proteins in blood samples from 1,300 individuals, 350 of whom are from Qatar, the research team was able to calculate the probability that the methylation of a certain gene affects the production of a specific protein. Once common factors that control DNA methylation, like age and gender were filtered out, the researchers then identified 98 direct correlations between the methylation of a specific gene and a protein. Taking it to the next stage, the researchers then used this information to ask whether there are further correlations between disease manifestations and specific proteins that could eventually link several conditions back to relevant genes.

The team has now published this work in the prestigious international journal Nature Communications under the title, Epigenetics meets proteomics in an epigenome-wide association study with circulating blood plasma protein traits.  

According to Dr Suhre their research lays the foundations for the development of new medicines and therapies as it connects proteins – which can be the targets for drugs – to fundamental biological processes and their dysregulation diseased individuals.

The research paper’s first author, Dr Shaza Zaghlool was responsible for the majority of the computational work and is also the bioinformatics research manager at WCM-Q. She said it was gratifying that the study may lead to the development of new disease therapies.

Connecting these huge genetic and protein data sets to disease information obtained from hundreds and thousands of individuals using sophisticated computing skills is like looking for a needle in a haystack, but it can also be very rewarding knowing that our findings may eventually help develop new cures.’

Dr Khaled Machaca, Senior Associate Dean for Research, Innovations and Commercialisation at WCM-Q, praised the support of Qatar Foundation for the work.

This multi-disciplinary work fully led by researchers based in Qatar has only been possible thanks to the visionary support from Qatar Foundation and its genomics, proteomics and bioinformatics cores who generated and analysed most of the data.’