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Twin Study Teases Out Genetic, Environmental Contributors To Immune Phenotypes

NEW YORK (GenomeWeb) – A new study has started unraveling the relative importance of genetics and environmental factors in immune response, suggesting more than two thirds of immune-related traits may be mainly controlled by heritable factors.

"Our study assists precision medicine by defining which human immune traits are under genetic or environmental control and, in particular, which are subject to common shared household exposures such as microbiota and diet," co-senior authors Tim Spector and Frank Nestle, researchers at King's College London, and their co-authors wrote.

Along with collaborators from the UK and the US, Spector and Nestle explored the heritability of immune responses, using data for nearly 500 female twins that measured tens of thousands of immune features. Their results, published online today in Nature Communications, indicated that environmental factors most profoundly affected almost one quarter of the immune traits. Almost 70 percent of the immune phenotypes, particularly those related to adaptive immunity, were more strongly affected by genetic factors.

"[M]ost immune responses are genetic, very personalized and finely tuned," Spector said in a statement. "What this means is that we are likely to respond in a very individualized way to an infection such as a virus — or an allergen such as a house dust mite causing asthma. This may have big implications for future personalized therapy."

The team noted that diverse sets of immune cell populations must act in a coordinated manner to protect from cancer, potential pathogens, or other problems, while avoiding excessive immune activity targeting an individual's own tissues.

In an effort to explore the environmental and genetic contributors to such processes, the researchers considered immune phenotypes in 497 female adult twins, including 75 identical twin pairs, 170 non-identical twin pairs, and seven singleton individuals.

Starting from more than 89,000 immune-related traits measured using flow cytometry-based immunophenotyping, the team used the twin data to estimate the relative genetic and environmental contributions to 23,394 of the most reliably measured immune-related phenotypes.

With these data, the team saw hints that innate immunity tends to be more strongly impacted by environmental contributors such as diet, childhood infections, or microbial exposures than by genetic features. Overall, the group estimated that some 24 percent of immune phenotypes are mainly affected by environmental factors.

On the other hand, aspects of the immune system that reflect adaptive immunity — such as CD4+ or CD8+ T cell activation — seemed to be more strongly influenced by genetic factors. All told, the researchers reported that genetics was the most pronounced contributor to about 67 percent of the immune phenotypes considered.

"[A]daptive immune responses, which are far more complex in nature, appear to be more influenced by variations in the genome than we had previously thought," co-first author Massimo Mangino, a twin research and genetic epidemiology investigator at King's College London, said in a statement. "In contrast, variation in innate responses (the simple non-specific immune response) more often arose from environmental differences."