Gene flow

Society shapes our "health destinies," reports landmark study

The way we grow up has a lasting effect on our genes.

Even if you move away from your hometown, upbringings stick around for life. Scientists increasingly understand that where and how we grow up profoundly shapes us emotionally, psychologically, and in some ways genetically. Where you're from leaves marks that, in some cases, manifest decades into adulthood. A new study, the largest of its kind, shows just how influential those marks are.

The stresses of society, like socioeconomic status or race, strongly influence the way genes are expressed, according to a study published Monday in the Proceedings of the National Academy of Sciences.

Researchers found significant differences in the way two types of genes are transcribed: genes related to inflammation (a pre-cursor of diseases like heart disease) and the immune system's ability to fight off viruses.

Later in life, these patterns of gene regulation may lead to chronic illnesses. But these study participants in this study were under the age of 37 — suggesting that the scene for certain diseases may be set early in life.

Steve Cole, the study's lead author and a professor at the University of California, Los Angeles, tells Inverse that this study shows just how much our circumstances affect our "health destinies."

"The most important takeaway is that the lives we lead shape the molecular function of our bodies and our long-term health destinies, even decades before the health consequences might become apparent in disease," Cole tells Inverse.

How demographics show up in genes

Your genes don't define you, but the past and present are entwined into our genetic code.

You inherit genes from your parents, and genes are also incredibly influenced by our environments. But because not all genes are being transcribed by the body all the time, current events, like sleep deprivation, or stress, can also affect which genes get transcribed.

The places and stresses we're exposed to in early adulthood have profound effects on our genes, according to the study's findings. Shutterstock

One way scientists measure how the environment affects gene expression is by looking at a transcriptome, which essentially is a giant catalog of all the genes that are being actively transcribed by the body.

"The lives we lead shape the molecular function of our bodies and our long-term health destinies."

In this new study, Cole and his colleagues examined the transcriptomes of 1,069 adults, whose data was collected from the National Longitudinal Study of Adolescent to Adult Health. The researchers also collected demographic data and took note of factors like body mass index, smoking or drinking.

Using those transcriptomes, the authors dug deep into two sets of genes: 19 proinflammatory genes and 32 genes related to defending the body against viruses. These two types of genes are important because they underpin one of the major ways scientists think that social disparities show up in our bodies.

Social disparities can drive high levels of stress, and in turn, constant stress can lead to changes in the way genes are expressed in the body. This specific shift is called a "conserved transcriptional response to adversity" (CTRA). Genes express a CTRA when people are exposed to a chronic threat, like poverty.

Previous work conducted by Cole suggests that this shift is characterized by more activity in inflammatory genes and less activity in genes related to defense against viral infections. CTRA is also associated with cancer and cardiovascular disease.

This study provides detailed evidence that this shift in gene transcription due to societal context exists, and it happens when people are very young.

"Because young adults are typically healthy, the demographic differences in gene activity that we're seeing in this sample aren't likely to be driven by differences in diagnosed diseases," Cole explains. "Instead, they appear to be consequences of the way we live, the life circumstances we inhabit, and probably also some genetic influences."

Patterns in gene responses

According to this research, the way our upbringings affect our genes fit into two major patterns: demographics and behavior.

Our behavior — like smoking, drinking, and behaviors that affect body mass index (BMI) — affects types of genes that are unaffected by demographics. These "biobehavioral" traits strongly affect genes related to inflammation.

Race and sex also influenced gene expression. The study notes that genes related to inflammation were significantly more active in females participants and in black participants, compared to non-Hispanic whites.

But when it came to the genes related to the immune system, individual demographics influenced gene expression more so than behavior.

While some of these differences may seem small, they help explain big patterns in human health. A 2017 paper inThe Lancet shows how stark this can be: In a sample of 1.7 million adults they found that those with low socioeconomic status were 1.5 times more likely to die before the age of 85.

This paper digs into the deep, biological details that underpin these large effects. The way we grow up can have profound effects on how our genes work, and how healthy we are later on. Certain factors, like poverty and systematic racism, are out of a child's control — yet the stress of those events do affect a child's health. While these factors are major hurdles, Cole approaches the subject from a place of optimism, saying "it's never too early to start trying to make things better by changing the world around us and the way we live."

Abstract: Health in later life varies significantly by individual demographic characteristics such as age, sex, and race/ethnicity, as well as by social factors including socioeconomic status and geographic region. This study examined whether sociodemographic variations in the immune and inflammatory molecular underpinnings of chronic disease might emerge decades earlier in young adulthood. Using data from 1,069 young adults from the National Longitudinal Study of Adolescent to Adult Health (Add Health)—the largest na- tionally representative and ethnically diverse sample with peripheral blood transcriptome profiles—we analyzed variation in the expres- sion of genes involved in inflammation and type I interferon (IFN) response as a function of individual demographic factors, sociodemo- graphic conditions, and biobehavioral factors (smoking, drinking, and body mass index). Differential gene expression was most pronounced by sex, race/ethnicity, and body mass index (BMI), but transcriptome correlates were identified for every demographic dimension an- alyzed. Inflammation-related gene expression showed the most pronounced variation as a function of biobehavioral factors (BMI and smoking) whereas type I IFN-related transcripts varied most strongly as a function of individual demographic characteristics (sex and race/ethnicity). Bioinformatic analyses of transcription factor and immune-cell activation based on transcriptome-wide empirical differences identified additional effects of family poverty and geographic region. These results identify pervasive sociodemo- graphic differences in immune-cell gene regulation that emerge by young adulthood and may help explain social disparities in the devel- opment of chronic illness and premature mortality at older ages.

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