Genotypes and Phenotypes: Why We Have Bipolar Disorder

Posted on June 25, 2015 in Bipolar Disorder Genes

There’s a mystery in the genetics report that I received from 23 and me and ran though the Promethease analysis engine: I have multiple genes that predispose me to lupus. I don’t have lupus but an uncle of mine did. It also says that I could develop multiple sclerosis and that I am at risk for childhood leukemia (I dodged that bullet.) My risk for bipolar disorder is only average. It also says that I am tall (true — I am 6′ 6 1/2″), probably have brown eyes, that risperidone works well for me, and have a tendency towards diabetes and obesity — right on all counts, though I am working to reduce my weight. All these things are in my genes. How is it that I show some of the predicted traits and not others?

Some might jump to the conclusion that genetics just gets these things wrong. No, the genes are there for certain. I am prone to lupus and MS. I could have had childhood leukemia. So why didn’t I if genes are the code that determines what I am? Why do I have bipolar disorder?

You must understand two related concepts: that of the genotype and the phenotype. The genotype is what is in our genes. Think of it as a data bank which the body uses when it constructs us, a series of rules that it follows when life happens to us. Back in the day, we used to have endless debates about whether it was “nature” or “nurture”. One side insisted that we were automatons determined by our genes. The other side said that we were wholly created by our environment, that culture and early childhood experiences shaped us around a blank slate. I remember — I was the moderate then as always — asking “Why can’t it be both?” Today most genetic, medical, and social scientists agree with me. We are not merely the sum of our genes or our experiences: the result is the phenotype, the combined expression of these two natural forces.

The automaton that is our genes reacts to everything that happens to us in our lives. Each of us have different histories. Some of them are the choices we make. Others are things that happen to us. Two people with the same genes will not necessarily exhibit the same traits. There are twin studies that have shown that one twin can develop schizophrenia while the other doesn’t. New research credits stress as an environmental factor that can predispose one to mental illness, for example: one twin might have been bullied or farmed out to an abusive foster home where the other was raised under more fortunate circumstances. (Many outspoken advocates for the AOT movement deny the environment — they reject the concept of the phenotype. Likewise, many antipsychiatrists deny the genetic angle. They, too, deny the phenotype.)

Why the hell did I end up with bipolar disorder? I think many things probably contributed including stress in my childhood and smoking marijuana. The one was a series of events over which I had little if any control. The other was a choice that I made, albeit under peer pressure and enticement, but still a choice. Other things might have happened, too.

But how does this work?

The best metaphor that I have heard came from a genetic counselor at a DBSA Convention in Indianapolis a few years ago. Imagine a beaker. At the bottom of this beaker put a few balls. We’ll color them blue. These represent your genetic inheritance. Now these alone won’t cause the symptoms of bipolar disorder. Start dropping in some orange balls. Each of these represents a degree of environmental pressure. As long as these don’t cause the beaker of balls to overflow, the symptoms won’t be expressed. When the beaker overflows, your bipolar disorder rears its ugly head. Here’s the rub: some people have only a few blue balls (everyone has some in this case) and some people have a lot of blue balls. So either it takes a lot of orange balls or not many at all. Some people have a very strong disposition towards bipolar disorder so it doesn’t take many orange balls at all to push them over the edge. Others, like me, show the symptoms because we have come under a lot of pressure from various factors — in my case a combination that I only partially understand.

Incidentally, the same uncle who developed lupus was the shortest man in a family of tall men. He had had rickets as a child.

So why don’t I have lupus or MS? Because orange balls don’t work for every disease: each has its own special set of risk factors. I was lucky as a child because I didn’t accumulate the kinds of environmental stimulants to cause me to develop childhood leukemia. So far, I haven’t developed enough of the risk factors for lupus or MS to trigger those diseases.

The moral of this story is that you are not damned by your genes. They are not a curse, they are not predestination. They are merely a blueprint that the blind engineer called Life can follow or ignore according to circumstances.

---

You might want to know the risk factors for lupus. Lupus is overwhelmingly a problem for women — more than 90% of the cases occur in females. Being of child-bearing age is another risk factor, so it turns up in most people between the ages of 18 and 44. If you are African American, Asian, Latino, Native American, or a Pacific Islander, you are more predisposed to lupus than if you are white. Finally, if you have a relative with lupus, there is a 5 to 13% chance that you will develop it, too. Children of lupus patients have only a 5% probability for having it, too.