Genetic study in Sardinia shines new light on disease and immunity

Precision medicine — using genetic and other biological information to better customize treatment of disease — continues to offer intriguing promise. Recently, a team of NIA-supported SardiNIA study researchers reported important progress toward clarifying how genetics influence the immune system, with potential implications for developing treatments for many autoimmune diseases. The scientists, who hail from Italy’s University of Sassari and the National Research Council’s Institute of Genetic and Biomedical Research, published their findings in Nature Genetics.

The SardiNIA study is comprised of about 4,000 longtime Sardinian volunteer participants. The Italian island, often described as a microcontinent, is home to geographically isolated genetic family trees that are more than 8,000 years old with little mixing from outside populations, making it ideal for research on how gene expression impacts health. Sardinia is also one of the world’s so-called “blue zone” cultures known for healthy aging and longevity. Previous analyses from the SardiNIA study identified gene associations with many variables that can contribute to anemia, gout, heart disease, and kidney disease.

Using genome-wide association studies of volunteers’ blood samples, the team clarified the influence of around 22 million DNA variants on blood levels of an unprecedentedly large number (more than 700) of immune cell variables or traits. The team found about 120 significant independent correlations or signals of specific DNA changes that affect over 450­ cell traits and identified other molecules important in immune cell regulation.

Overall, this study expanded by close to 80% the number of known genetic associations with immune cell traits. About half of these genetic signals also overlapped with previously reported disease-associated signals, mainly for autoimmune disorders. This genetic scan also revealed cases in which a known drug affects risk of several diseases or several different immune cell types, sometimes in opposite directions. The data therefore provided clearer understanding of the mechanisms underlying these associations and helped to explain the efficacy, failure, and side effects of some treatments.

By providing a better biological understanding of how autoimmune diseases develop, these findings can inform the development of treatments. The results can also guide future analyses of how specific immune cells and molecules interact in autoimmune diseases like multiple sclerosis, lupus, rheumatoid arthritis, ulcerative colitis, and type 1 diabetes.

This research was supported in part by the NIA Intramural Research Program.

Reference: Orrù V, et al. Complex genetic signatures in immune cells underlie autoimmunity and inform therapy. Nature Genetics. 2020;52(10):1036-1045. doi: 10.1038/s41588-020-0684-4.

Courtesy: National Institute of Aging, USA

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