From Risk to Resonance: Rethinking What Genes Really Tell Us
“What we call fate is a question we stopped asking.” Kevin Rigley
Introduction
Today, understanding our genetic code is more straightforward than ever. By simply providing a saliva sample, we can discover information about our ancestry, our risk for certain diseases, and even some of our behavioural traits. One tool employed in this expanding field is the Polygenic Risk Score (PRS), which is a figure that estimates our likelihood of inheriting conditions such as depression, ADHD, schizophrenia, or autism.
But what exactly is a PRS, and where does it come from? A Polygenic Risk Score (PRS) is created by looking at many tiny changes in our DNA, called single nucleotide polymorphisms (SNPs). These changes add a small bit to the overall chance of getting a specific health condition. When you combine and adjust these changes, you get one number that represents your risk: your PRS. It’s a score that doesn’t determine your fate — but claims to reflect your statistical susceptibility based on how people with similar genetic profiles have fared in large-scale studies.
And yet, this concept — while seductive in its precision — is widely misunderstood.
Here’s the issue: PRS (Polygenic Risk Scores) are often misunderstood. People usually think of these scores as predictive. A high PRS? That probably means the condition is in your genes. A low PRS? You might think you’re safe. But that’s not quite how biology works — or how life progresses. PRS shows something more nuanced and significant: a sensitivity that depends on circumstances. Genes don’t directly cause outcomes. Instead, they can show what might happen, but only if the environment allows it.
Simply put, a Polygenic Risk Score doesn’t determine your future. Instead, it shows how much your environment might activate a certain biological potential. This change in viewpoint is significant; it changes how we see disorders, personal growth, and accountability. If results rely on the environment, then it’s the environment — not just our genes — that truly influences what happens to us.
And in the Anthropocene, we are the architects of context.
What Is PRS — And What It Isn’t
Taken together, the PRS is a weighted score that tells us: “People with this profile are more likely to develop Condition X.” For example, someone might be told they have a 65% higher risk of developing depression or a 1.4 times greater likelihood of being diagnosed with autism. These numbers feel precise and medical, and predictive.
What PRS actually provides is not destiny but rather probability across a population. It doesn't claim you will develop depression; it indicates that individuals like you, in similar environments, have demonstrated a statistical tendency toward that outcome.
Here’s the catch: PRS does not model the environment. It assumes a sort of “average” background context — an unspoken constant throughout the dataset. However, no environment is truly average. Context is everything.
That means two people with the same PRS could have very different lives. One might struggle with severe mental health issues, while the other might never experience symptoms at all. Why? because their environments—emotional, social, and biological—are not the same. And so, PRS isn't a measure of genetic fate. It’s a measure of environmental dependency—misunderstood as genetic certainty.
Understanding this single point reframes what genetic risk really is. It opens the door to a different paradigm: not one of predisposition but of potential conditioned by context. And that’s where we turn next.
The Conditional Gene — A Slave to Its Environment
No matter how powerful its potential, every gene requires a context — a biochemical, cellular, social, and ecological environment — to be expressed. It’s not the gene that becomes something else, but the expression of the gene that emerges varies or remains silent depending on the environment. This is the fundamental truth modern biology has taught us:
Genes are not blueprints. They are instructions that are read — or not — depending on environmental conditions.
This process is regulated through epigenetics — mechanisms like DNA methylation and histone modification that control which genes are activated, when, and to what extent. In effect, epigenetics is the dimmer switch of development, modulating gene expression in response to external stimuli — from prenatal nutrition and stress, to emotional bonding and toxin exposure.
So when a Polygenic Risk Score suggests a heightened chance of developing, say, schizophrenia, it’s not saying the genes will make it happen. It’s saying:
“If the right (or wrong) conditions are met — if the switches are flipped — then this particular expression becomes likely.”
Which leads to an even deeper realisation:
What we refer to as “genetic risk” actually measures vulnerability to environmental activation.
And that changes the game entirely.
It means the gene is not causal by itself. It is conditionally deterministic — it acts only if the environment allows. It expresses only when triggered. In this sense, the gene is a slave to its environment, entirely dependent on it for the manifestation of meaning and relevance. Even at the most basic molecular level, this dependency remains true.
DNA, often envisioned as the driving force of life, remains biologically inactive without the proper environment. Its codons may provide the blueprints for mRNA, yet without free nucleotides, energy, and the various molecular machinery of the cell, those blueprints are rendered useless. No transcription. No translation. No expression.
In this perspective, the genome does not act as a dynamic cause; rather, it serves as a passive archive. It functions as a library filled with possibilities that only spring to life when the environment supplies the essential tools, signals, and context. Absent these elements, DNA isn’t a blueprint — it’s a silent string of letters.
Think of it like the alphabet: the same set of 26 letters can be used to write a love poem, a war cry, or nothing at all. It’s not the alphabet that determines the message — it’s the writer, the context, and the intent. Likewise, the genome only speaks when the environment provides the language in which it can be read.
So when PRS appears to indicate there is a “65% risk,” it’s not measuring the power of the gene. It’s assessing the likelihood that the triggering environment will exist. In the presence of that environment, the risk becomes a reality. In its absence, it remains silent.
Introducing PPS — From Genetic Risk to Polygenic Potential
If genes are conditional, and PRS merely reflects their context-dependent sensitivity, then the concept of “risk” is misleading. Risk implies something negative is likely to happen. But genes don’t carry intentions. They don’t know good from bad. They respond to what is.
So what if we stopped framing genetic profiles in terms of risk, and started framing them in terms of potential?
Enter the Polygenic Potential Score (PPS) — a reframing of genetic influence that centres not on pathology but on capacity. Where PRS looks for the likelihood of developing a disorder, PPS asks:
Given the right environment, what are the adaptive traits this genome is prepared to express?
PPS shifts our thinking from fear to possibility. It allows us to see individual genetic profiles as sensitivity maps — blueprints for what a person might learn, process, feel, or excel in, if the conditions are present.
Consider this: one person may excel in verbal fluency, another in visuo-spatial problem solving, and another in novelty-seeking, social atonement, or pattern recognition.
These aren’t “disorders” — they’re dimensions of developmental diversity.
And like any dimension of potential, they don’t manifest automatically.
They emerge when the environment allows for their emergence.
That’s the beauty of PPS: it doesn’t predict what will go wrong. It tells us what might go right if nurtured correctly.
It’s not deterministic.
It’s dynamic.
It’s not diagnostic.
It’s developmental.
It doesn’t ask, “What are you at risk of?” It asks, “What are you capable of becoming?”
The Missing Half — Polygenic Environment Score (PES)
If the Polygenic Potential Score (PPS) describes what a genome can achieve under optimal conditions, we need a systematic method to define those conditions rather than vagueness terms. This is where the Polygenic Environment Score (PES) comes in. PES is the environmental complement to PPS—a way of measuring an environment's developmental quality, not in absolute terms but in terms of its enabling capacity for gene expression.
PES is not just about “good” or “bad” environments. It’s about how tuned a particular environment is to the expression of a particular potential.
Take education, for example. A classroom might have:
High structure but low relational warmth.
High sensory input but low predictability.
Rich cognitive material but rigid expectations.
Is that a good environment? It depends. It may be ideal for a child with high PPS for rule-seeking and cognitive abstraction, but it may be overwhelming or suppressive for a child with high PPS for sensory sensitivity and emotional nuance.
PES, then, is a measure of fit — of resonance between potential and context.
It invites us to map environments using dimensions like:
Predictability vs. chaos
Stimulation vs. overload
Emotional availability
Social patterning
Cognitive flexibility
Noise, stress, and relational density
Then, match those scores to individual PPS profiles—not to stream or label, but to enable expression. In this framework, environments are no longer neutral backdrops.
They are active forces in shaping which versions of ourselves come forth — and which remain silent.
Because what we call "development" is really a conversation. The genome offers an alphabet, and the environment decides what language will be spoken.
The Matrix of Expression — From Probabilities to Equilibria
When we combine the Polygenic Potential Score (PPS) with the Polygenic Environment Score (PES), we don’t get a prediction — we get a state space. A landscape of possible outcomes shaped by the interaction between internal sensitivity and external context.
And within this space, all outcomes are not random but adaptive equilibria.
Every condition, behaviour, or trait we observe is an equilibrium — a stable resolution between what the genome is prepared to do and what the environment demands or permits.
This model moves us away from diagnosing dysfunction and toward understanding adaptation.
A so-called “disorder” may be an adaptive solution to a misaligned PES.
A child labelled inattentive in a low-flexibility PES may thrive in an exploratory one.
A heightened emotional response may be the right adaptation to an unpredictable relational environment.
When we look at outcomes this way, the moral question shifts from “What’s wrong with this person?” to “What equilibrium has their biology settled into — and why?” This is not disorder. This is adaptation under constraint. And if we want to change the outcome, we don’t have to fix the person. We have to reshape the environment. And that shift — from individual blame or pride to systemic reflection — is where real change begins.
The PRS made us look inside the individual. PPS and PES ask us to look at the ecosystem.
Rather than celebrating neurodivergence in isolation, we must ask: What adaptive logic is this expression fulfilling? What structural realities has this neurotype emerged in response to?
We don’t yet understand the full mechanisms, but the trend is unmistakable. Consider the rise in neurodivergent conditions. Are we becoming more autistic, anxious, or inattentive—or are we simply developing brains in environments that demand these adaptations? This is not about blame; it’s about causality. It’s about focusing our attention on the world we've created and the subtle, often invisible pressures it places on developing minds and bodies.
But this perspective overlooks the fact that genes do not act unless the environment provides them with a reason to do so. Therefore, we must ask: What is it in the environment to which my genes are responding?
This inward gaze has social consequences. It encourages a kind of genetic fatalism: “It’s not my fault—it’s my genes, " as if the genome alone wrote the story.
A high PRS warns us, “You are at risk.” However, it diverts attention from the context that transforms that risk into reality. It views the genome as the cause rather than the responsive canvas that it truly is. Polygenic Risk Scores appear to provide clarity — a numerical readout of our biological destiny. Yet, their alluring precision often leads us into a trap: the trap of looking inward when we should be looking outward.
The PRS Trap — Why Looking Inward Blinds Us to Causality
For most of evolutionary history, the environment was given mountains, rivers, storms, and predators — forces beyond our control. The brain adapted to these conditions in ways that were functional, amoral, and often invisible. Nature had no intentions. It simply was.
But in the Anthropocene, that equation has flipped. Today, the environment that shapes our development — our cognition, attention, emotion, stress response — is largely human-made. It includes:
Social systems
School curricula
Urban noise
Digital algorithms
Economic precarity
Institutional expectations
We’ve become the designers of the very context in which biology expresses itself.
And here’s the catch: When we shape the environment, we inherit its causal power and its moral implications with it.
The old excuse — “It’s genetic” — no longer lets us off the hook. Because what genes do depends on what we’ve built around them. A child adapting to overstimulation, surveillance, or isolation is not broken. That child interprets the world we created and responds in kind. Their “disorder” is our design reflected to us.
This is the mirror the PPS–PES framework holds up:
Not just what are we seeing?
But what are we causing?
And what kind of environments do we have the courage to build instead?
Biology lacks moral weight, but design holds it. Now that we are part of the environment, we bear responsibility for what it permits to emerge.
Conclusion: From Understanding to Design
We began with a number — the Polygenic Risk Score — a figure that claims to predict who we are or might become. But as we’ve seen, PRS doesn’t measure destiny. It measures sensitivity. It reflects the probability that a person’s biology will respond — not to their genome alone, but to the world in which that genome unfolds.
In this light, outcomes are not errors. They are equilibria. They are adaptive expressions of what it means to grow up — and live — in a particular context.
And context, now more than ever, is human-made.
The rise in neurodivergent expressions, mental health diagnoses, and developmental “disorders” is not just a story of genes. It is a story of environments — social, educational, digital, ecological — that we have designed.
We are no longer passive observers of nature. We are nature’s architects. And that gives us both power and responsibility.
The PPS–PES model doesn’t ask us to fix people. It asks us to understand potential — and to design environments that let it unfold with dignity.
Because behind every score is a signal. Behind every label, an adaptation. And behind every adaptation, a mirror: A reflection of the world we’ve made — and the chance to imagine a better one.
And here lies the irony. In physical health, we’ve already accepted that the environment shapes biology. We don’t blame genes for Type 2 Diabetes — we blame sugar, stress, and lifestyle. We understand metabolic epigenetic modification (MEM): how what we consume, breathe, and absorb alters gene expression over time.
We’ve even reframed dementia as Type 3 Diabetes — an environmentally mediated breakdown of metabolic-cognitive pathways.
But in cognitive and emotional health, we still hesitate. We still blame the child. We still say, “It’s just how their brain is.” Where is our CEM — Cognitive Epigenetic Modification?
Where is the model that says: “This child is not broken — they are becoming who the environment has taught them to be”? Until we adopt CEM, we will keep treating expression as an error and ignore the more profound truth:
Like the body, the brain is always in conversation with its context. It is time we listened to what it was trying to say.