Breakthrough Research Connects Genes, Personality, and Health




Once upon a time, our parents’ social standing fixed us in place. Then our genetic inheritance. Then our environment. Nature, nurture, nature, nurture—back and forth the pendulum swung, which should have been a clue that the right choice was both. Even after we figured that out, though, we still thought in terms of single genes, operating in isolation to cause particular traits or doom us to particular illnesses. Then—the start of nuance—we began talking about single genes predisposing us to certain personalities or conditions. But if a geneticist was talking, genes had the strongest influence, and if a social scientist entered the conversation, they shifted the weight to the environment.

Only now is it clear that genes network like busybodies, responding to every possible influence and turning one another on and off as the situation demands. “Personality is complex, shaped by biogenetic, sociocultural, psychosocial, and environmental influences,” says Dr. C. Robert Cloninger, professor emeritus in psychiatry at Washington University. What a muddle we are, then. Why even try to fathom it?

Because personality is one of the strongest predictors of our overall well-being and physical health. Cloninger and other researchers make this point in a study just published in Molecular Psychiatry (part of Nature’s prestigious portfolio).  Using AI and four decades of genetic and health data, this study is the first to connect human personality with the way our DNA is transcribed to RNAs, which then do the work of adapting to changes in our internal and external environment.

We might rush to scrape our gums and mail off the sample, but “23andMe is not telling us much about our health,” Cloninger notes dryly. “A single gene is not enough to cause or protect against disease. When people just collect a DNA sample and tell you, ‘This is your risk,’ they are nowhere close. If you only measure the DNA in the genome, you don’t know how they are transcribed, put into action, regulated, and choreographed. We need a whole new way of understanding mind and body.”

It was Cloninger who first identified four measures of temperament that can be inherited: how eagerly we seek novelty; how assiduously we avoid harm; how dependent we are on reward; how persistent we are. Then he added dimensions of character that are far more malleable: how self-directed we are, how cooperative, how self-transcendent. Since then, he has gathered genetic data from thousands of individuals on every continent. First, his research teams identified 972 genes that are directly associated with personality. These genes are organized as three systems of learning and memory, and those systems shape and adapt our responses to changing conditions. The first system conditions habits and skills; the next gives us self-control, to shape our own goals and values; and the third instills self-awareness, making autobiographical memory and creativity possible.

Next, the researchers identified more than 4,000 additional genes that are indirectly associated with personality, including two smaller networks that regulate the way all the genes for physical, psychological, and social functioning are expressed. One network regulates our emotional reactions; the other regulates our interpretations of meaning.

In the new study, the team has located a hub of six genes that act as symphony conductors, orchestrating the constant flow of interactions between those two regulatory networks. This control hub allows us to integrate and coordinate all three systems of learning, and it remains active whether we are awake, asleep, or anesthetized. In other words, our personality remains at work subconsciously throughout our lives. And that personality is not static; it can develop for better or worse as we adapt to changes in circumstance, the “slings and arrows of outrageous fortune.”

The personality’s control hub regulates specialized modules for different aspects of our lives—physical, mental, social, and spiritual. To adapt to constant change, these modules turn one another on and off, which means that who we are is never fixed in place.

The study’s conclusions give scientific weight to insights once relegated to ethics, therapy, religion, and wellness. There is such a litany of illnesses exacerbated by “stress” that we have gone numb to the word. Stress is the inevitable symptom of modern life, and it seems to make everything worse. But Cloninger puts this truism in context, explaining that the most damaging kind of stress is feeling separate and defensive, embattled, competitive and aggressive (or compliant and secretly resentful). What counters that stress is not Peloton or polyamory or quiet quitting. It is the awareness—swept for centuries into the mystical corners of every world religion—that we are not alone. We are part of a larger, undivided whole.

Cloninger’s team slid that transcendent self-awareness from mysticism into medical science. Until now, personality researchers have resisted any mention of self-transcendence. It sounds woowoo, insufficiently secular, utterly unscientific. “Yet it turns out to be the biggest driver of health,” he says. “When we feel threatened or antagonistic, the body is fighting back. It’s not trusting.” He pauses. “When a population is as stressed as ours is, you get increases in most diseases.”

The counterweight is transcendent self-awareness, a spiritual concept whose importance can now be shown scientifically. Cloninger’s team collected blood, identified gene clusters, assessed temperament and character and lifestyle, and observed the 972 personality-related genes as they interact with thousands of other genes.

Guided by our level of self-awareness, as measured by our personality, the six little symphony conductors in the hub stay busy transferring information between networks, turning genes on and off. This regulates how well-coordinated we are, and thus our level of well-being. Put another way, self-awareness is transcribed and translated, at a molecular level, into well-being. The upshot? We are freer than some philosophers would have us believe, with our health and future less determined. If, that is, we are self-aware and flexible, able to break free of our ego’s constraints and sense our connection with the rest of the universe.

Why would emotions and ego interfere with our mental, emotional, physical, and spiritual health? Because our emotions are often irrational, and our ego is a scrappy little entity, defensive and constantly fighting, competing, scheming for its own rewards. Well-being comes when people set those games aside, seeing themselves as part of a larger, undivided, interdependent whole.

How do we get there? By relaxing, letting go of fights and worries, doing kindnesses for others, trading irritability for calm, cultivating self-awareness through meditation, and becoming sensitive to the arts and humanities. “All parts of ancient wisdom,” Cloninger points out, “but we hadn’t had a model you could measure. Now we see that your level of insight allows you to express your genome differently—and that affects every aspect of well-being. The ability to realize you are part of the whole is what motivates a truly healthy life.”

He offers more detail about those three levels of insight and awareness that, ideally, we can all access. At the first level, we learn by habit, custom, and tradition. But if this is the personality’s dominant mode, we are in trouble, because it involves little or no rationality or self-awareness. Without self-awareness, we are emotionally reactive, driven by habits and irrational emotions, vulnerable to authoritarian leaders.

At the second level, learning and memory are more organized and analytical. We are self-sufficient, self-directed, and deliberate, capable of cooperating with others if it suits our needs. But if this level dominates the personality, our self-awareness is still bounded by ego, and our goals stay self-centered and materialistic.

At the third level, self-awareness is transcendent. We are aware of our connections to one another, to nature, to all of existence. This is the creative level, the place where the ego relaxes and compassion, patience, social conscience, and altruism are possible. Gratitude and humility replace arrogance. Defensiveness and combativeness dissolve.

We can all learn in all three ways; they overlap and integrate. What influences our personality is which way dominates. And if the third level dominates, we see increases in every aspect of well-being.

Here is the wild part: science confirms spirit. The molecular interactions at each of those three levels are entirely different from one another. And at the third level, what religion calls “soul” is translated into the personality features of self-transcendence. Our emotional responses and interpretations of meaning activate molecular genetic mechanisms which yield an outlook of unity. From that vantage point, we are inspired by the age-old virtues of love, hope, and faith—not greed or blind obedience—and we have the flexibility and freedom to put this inspiration into action.

Cloninger had begun his career trying to reduce personality to heritable temperament traits only. When he realized that was, indeed, reductive, he added the three dimensions of character. Then he kept going, uncovering the complexity of personality and how it allows us to adapt, flexibly, to survive in an evolving world. In a study that led to the current research, he teamed up with colleagues in many parts of the world, and they showed, empirically, that personality explained nearly half of the variance in participants’ happiness and more than one-third of the variance in their wellness. Now they had even more clarity about how, and why, the personality wields such influence.

By regulating the way certain genes are expressed, character can influence the immune system, lessen inflammation (which flares with anger, anxiety, and depression), and regulate “brain functional connectivity” (the way different brain regions synchronize their activity to work together even at a distance). The internal peacefulness that results can help us heal or stay resilient.

Mind and body are even more deeply connected than we realized—and in ways that can be changed. Temperament might be welded from habits and traditions, but character is a kaleidoscope of possibilities. A willing shift in goals, intentions, or values can make us more self-directed, more compassionate, more aware of ourselves and others. That new perspective better regulates our emotions and desires, and it alters how we interpret life events. The resulting change in molecular interactions deep inside the brain has a powerful effect on every aspect of well-being.

“Genes can promote compassion and creativity, an outlook of unity,” Cloninger sums up, “rather than the defensiveness and inflammatory reactions that come from an outlook of separation.”


Read more by Jeannette Cooperman here.