A study carried out by scientists in the U.K. and Australia from the Cambridge Baker Systems Genomics Initiative shows that variants in some genes may predispose people to developing autoimmune diseases or allergies from an early age.
Autoimmune diseases such as type 1 diabetes, rheumatoid arthritis and inflammatory bowel diseases affect around 7% of the US population and even more, around 20% or higher, have some form of allergy.
Some people are known to have a genetic predisposition for autoimmune disease, allergies or both, but as the environment also plays a strong role, it’s hard to pin down how strong a role genes play and how early gene expression can play a role in the onset of these health problems.
To investigate this further, the researchers extracted cells from the cord blood samples of 152 neonates who participated in a cohort study about childhood asthma. They looked at two different types of immune cells from the blood—myeloid cells and T cells—then studied how these cells expressed certain genes and responded to different chemicals known to stimulate the immune-system.
“We looked for overlap between these genetic signals and those that are known to be associated with diseases where we know the immune system plays a role,” said Michael Inouye, Baker Heart and Diabetes Institute, Melbourne, who led the research project and was corresponding author on the study published in the journal Nature Communications.
The team then used statistical analysis to estimate links between the genetic responses they observed in the neonatal cells and autoimmune or allergic conditions in adults.
They found that changes in expression in some genes could be linked to later health issues. For example, in the gene BTN3A2, which encodes a protein thought to be involved in the adaptive immune response, and the gene HLA-C, which helps present new molecules to the immune system so it can decide whether they are ‘foreign’ or not.
“Our study showed the potential roles of gene expression in disease development, which has helped us to better understand the link between DNA variation and disease risk,” commented Qinqin Huang, now a researcher at the Wellcome Trust Sanger Institute in Cambridge and first author on the study.
“To date, similar studies have only been conducted in adult immune cells. Given the huge difference between neonatal and adult immunity, it is not surprising to see many signals that were unique to newborns.”
This study is just one part of the wider UK-Australian collaborative work that the Cambridge Baker Systems Genomics Initiative is overseeing. They are developing a variety of genomic risk scores to try and better estimate the likelihood of an individual developing different chronic diseases. For example, researchers working as part of the initiative have already developed genetic risk scores that can estimate risk for stroke and some forms of cardiovascular disease.
“Common diseases, such as type 2 diabetes and cardiovascular disease, tend to be polygenic – influenced by a large number of genetic variants scattered throughout the genome, which combine with environmental and lifestyle factors. By using new genomic technology and supercomputing capabilities, we can sift through this DNA data and piece together the puzzles that underlie each disease,” explained Inouye.
“We’ve shown this can be dissected using genetics and polygenic risk, hopefully leading to targeted preventative interventions for those who need them most, with the aim of keeping people living healthier for longer.”