Published: 15-01-2015 18:05 | Updated: 16-01-2015 10:16

Environment drives human immune variation more than genes

A study of twins conducted by Swedish and American investigators shows that our environment, not our heredity, plays the starring role in determining the state of our immune system, the body’s primary defense against disease. This is especially true as we age, the study indicates. The findings are being published in the journal Cell.

Much has been made of the role genes play in human health. Stunning advances in gene-sequencing technologies have caused many scientists to focus to minute variations in the genome, in the hope of predicting people’s future health. Such studies have revealed genetic contributions to health outcomes. But, with some notable exceptions, very few of those individual genetic variants seem to contribute much in particular health conditions.

To determine nature’s and nurture’s relative contributions, scientists at Sweden’s Karolinska Institutet and Science for Life Laboratory (SciLifeLab) together with colleagues at Stanford University in the United States turned to a century-old method of teasing apart environmental and hereditary influences: They compared pairs of monozygotic twins — best known to most of us as “identical — and of dizygotic, or fraternal, twins. Monozygotic twins inherit the same genome. Despite inevitable copying errors when cells divide, which cause numerous tiny genetic divergences to accumulate between monozygotic twins over time, they remain almost 100 percent genetically identical. Dizygotic twins are no more alike genetically than regular siblings, on average sharing 50 percent of their genes.

Sophisticated laboratory methods

Because both types of twins share the same environment in utero and usually share the same environment in childhood, they make excellent subjects for contrasting hereditary versus environmental influence. For the new study, the researchers recruited 78 monozygotic-twin pairs and 27 pairs of dizygotic twins from the registry and then applied sophisticated laboratory methods to participants’ blood samples to measure more than 200 distinct immune-system components and activities.

“Examining differences in the levels and activity states of these components within pairs of monozygotic and dizygotic twins, we found that in three-quarters of the measurements, non-heritable influences such as previous microbial or toxic exposures, vaccinations, diet and dental hygiene trumped heritable ones when it came to accounting for differences within a pair of twins”, said lead author Petter Brodin, MD, PhD at SciLifeLab and Karolinska Institutet’s Department of Medicine, Solna. “This environmental dominance became more pronounced when divergences between young identical twins, under the age of 20, were compared to those much older twins, ages 60 and up. Even traits that correlated quite strongly within these pairs in youth often lost that correlation in advanced age.”

The research team also observed considerable environmental influence over the quantities of antibodies produced in members of twin pairs who had been vaccinated for influenza. While many previous studies have suggested a powerful genetic component in vaccine responsiveness, Brodin et al noted that those studies typically were performed in very young children who had not yet undergone the decades of environmental exposure that appears to reshape the immune system over time.

Chronic carriers of cytomegalovirus

In a striking example of the immune system’s plasticity, the study found that the presence or absence of a single chronic, viral infection could have a massive effect on the system’s composition and responsiveness. Three out of five Americans and as many as nine out of 10 people in the developing world are chronic carriers of cytomegalovirus, which is dangerous in immune-comprised people but otherwise generally benign. In 16 of the 27 monozygotic twin pairs participating in the study, one member of the pair had been exposed to cytomegalovirus but the other had not. For nearly 60 percent of all the features measured, cytomegalovirus’s presence in one twin and absence in another made a big difference.

“Non-heritable influences, particularly microbes, seem to play a huge role in driving immune variation,” said senior author Mark Davis, PhD, professor of microbiology and director of Stanford’s Institute for Immunity, Transplantation and Infection. “At least for the first 20 or so years of your life, when your immune system is maturing, this amazing system appears able to adapt to wildly different environmental conditions. A healthy human immune system continually adapts to its encounters with hostile pathogens, friendly gut microbes, nutritional components and more, overshadowing the influences of most heritable factors.”

The work was funded principally by the National Institutes of Health, the Howard Hughes Medical Institute, the Wenner-Gren Foundation, and the Sweden-America Foundation.


Variation in the human immune system is largely driven by non-heritable influences
Petter Brodin, Vladimir Jojic, Tianxiang Gao, Sanchita Bhattacharya, Cesar J Lopez Angel, David Furman, Shai Shen-Orr, Cornelia L Dekker, Gary E. Swan, Atul J Butte, Holden T Maecker, Mark M Davis
Cell online 15 January 2015