Immune cell atlas helps explain the genetic causes of disease
A new study sheds light on one of the major mysteries of genetics: how disease-associated genetic variants influence the functioning of the human body. Based on more than 10 million immune cells, the atlas demonstrates how changes in regulatory regions of DNA influence gene activity and could help pave the way for the development of new treatments for serious diseases in the future.
The study was published in Nature and conducted by researchers from the Broad Institute, Massachusetts General Hospital, and the University of Helsinki in collaboration with the Finnish Red Cross Blood Service and BioBank Japan.
Previous studies have identified thousands of genetic differences that influence an individual’s risk of disease, but understanding their biological mechanisms has proven far more challenging. One reason is that many disease-associated genetic variants are not located within genes themselves, but in extensive regions of DNA that regulate gene activity.
Researchers have now developed a new method for linking disease-associated regulatory variants to the genes they regulate. Such variants are particularly likely to influence disease risk when they alter chromatin accessibility, or the openness of DNA, in a way that subsequently changes the expression of a specific gene. This discovery could help researchers identify which genetic variants are most relevant to a particular disease.
The study analysed more than 10 million immune cells from over 1,100 Finnish blood donors. The data were collected as part of the FinnGen research project and used to create a comprehensive atlas of immune cells. The atlas revealed likely molecular mechanisms through which tens of thousands of genetic variants influence hundreds of diseases and health-related traits. These include autoimmune hypothyroidism, inflammatory bowel disease, asthma, Alzheimer’s disease, and skin cancer.
The researchers also found that the body’s most important genes are regulated by large numbers of weak regulatory elements rather than by a single strong regulatory factor. This so-called regulatory buffering helps maintain stable gene expression and protects genes from the effects of individual genetic changes. The finding also helps explain why the functions of many key genes have been difficult to study using traditional methods.
The study provides a powerful new tool for investigating the biological mechanisms of disease and could help identify new targets for drug development in the future. The researchers have made their data openly available to the scientific community and will next focus on studying immune cells directly from diseased tissues rather than relying on blood samples from healthy individuals.
Population-scale immune multiome atlas reveals regulatory disease mechanisms | Nature
