My Beautiful Genome

by Lone Frank

  You are more vulnerable and susceptible to stress and strain than most people. It is important that you have supportive people around you to lean on.

  VULNERABLE BUT DISAGREEABLE. This is unquestionably a bad combination – whether you consider it from the inside or the outside. But where does it come from?

  According to science, I can put a large part of the blame on my parents and the genes they passed on to me. When you investigate the evidence, there is a surprising amount of genetics in our personality. Generally speaking, as measured by the Big Five test, personality is around fifty percent heritable, and a major meta-analysis of previous twin studies indicates that the individual dimensions vary in heritability from forty-two percent for agreeableness to fifty-seven percent for openness. That means the impact of genes and environment is more or less equal.

  Yet, the environment that matters may not be what you expect. “Behavioural-genetic research provides the best available evidence for the importance of environmental influences, but it shows that the environment works in a surprising way,” writes the psychiatrist Robert Plomin in a thorough review of the topic. You’d expect that your childhood home and the way your parents raised you would have a huge influence, but the environment that really matters seems to be anything other than what your parents create.

  Initially, this conclusion faced an uphill battle. In fact, when Plomin and his colleague Denise Daniels first published this conclusion in their 1987 article “Why Are Children in the Same Family So Different from One Another?,” it hit psychological circles with shock and awe. By analyzing previously conducted twin studies and adoption studies, Plomin and Daniels showed that neither personality nor psychological development is shaped by the environment siblings share when they are growing up. At least, that is, if their upbringing is not marked by outright abuse or neglect. This point was most clearly illustrated in research with children who, as toddlers, had been transplanted into adoptive families and raised with children unrelated to them by biology. If upbringing strongly influences personality, you would expect that children raised together would resemble each other more in personality than two random people off the street. But they don’t. The environment that influences personality, argued Plomin and Daniels, is what is called non-shared environment – the environment you don’t share with your siblings.

  Nailing down what counts as non-shared environment has proved difficult. One of the better proposals comes from an American researcher, Judith Rich Harris, who in her groundbreaking and controversial 1998 book The Nurture Assumption argues that as children we are colored by our peer group. The large component of personality that Mom and Dad are unable to influence is shaped by our same-age friends, with whom we try with all our might to fit in.

  Harris’s idea gained support from work by the Newcastle University psychologist Daniel Nettle. In Personality: What Makes You the Way You Are, published in 2007, he offers a twist on the peer group approach, claiming that the environment’s influence on our personality has to do with the world’s reaction to us. Our appearance and our intelligence affect how we are received by others, and the reaction of others is reflected back and incorporated into our personality. This ping-ponging helps regulate where, on a sliding scale, the five factors or personality dimensions are placed for an individual. When tall men, for example, score lower on agreeableness and higher on extroversion than comparable men of average height, it is because they do not need to please anyone, Nettle points out. Most people, as a starting point, are positively inclined toward tall men.

  All this is not to say that parents mean nothing – they can, indeed, cause their children lasting harm from the way they choose to run their family. Parental influence can easily shape the way you are within the family throughout your life. But as Nettle puts it, “The point is that this does not generalize to the adult personality with which the offspring addresses the rest of the world.”

  How am I to understand my own social robustness – or disagreeableness, if you will? Right off the bat, you might say, echoing Henrik Skovdahl Hansen, it corresponds precisely to my upbringing, which therefore must be its cause. But it could also come from my biological heritage. Perhaps I simply inherited some of the genetic elements that also made my father indifferent to the opinions of those around him. Or, to make it even more complicated, could it have to do with the fact that my genetic disposition fits particularly well with the way I was brought up?

  “IT WILL JUST be five minutes, but come in and take your coat off.”

  Gitte Moos Knudsen is trying to get three major funding applications sent off before the deadline in ten minutes’ time. Still, she looks remarkably tranquil sitting at her computer, and the spacious Copenhagen University Hospital office, with abstract art on the walls and Arne Jacobsen furniture swathed in light grey leather is virtually immaculate. The only signs that the young professor has had a rough day are her slightly reddened eyes.

  “Oh, it used to be worse when they wanted a dozen copies of each application,” she says, beaming with vigor and equanimity. I happen to know she is the type who bikes the eight miles to and from work – even when it is so cold that the gears freeze up. So when she asks me, after a little, whether I would like some warm milk in my coffee, I feel like a poor specimen of the human race.

  What has she seen, I think, as I take the cup. As research director of the Center for Integrated Molecular Brain Imaging, Moos Knudsen possesses a lot of data on me: a brain scan, a battery of tests on my cognitive abilities and social understanding, twenty-four hours of measurements of the stress hormone cortisol, and questionnaires on everything from sleep rhythms to personal problems. I’ve already learned about my skills in cognition – memory, verbal capacity, that sort of thing – and there is nothing to worry about there. I’ve also learned, quite surprisingly, that my social understanding lands at the high end of the spectrum. This afternoon, I’ve come to get the results of my genetic analyses. It’s nerve-wracking.

  To bolster myself, I decide to share a quotation that I picked up from the British psychologist Wendy Johnson: “Understanding genetic mechanisms for personality traits is one of the biggest mysteries facing the behavioral sciences.”

  Moos Knudsen nods and pulls her chair up to the round conference table.

  “We’re interested in behavior and personality, because they are also risk factors for psychological illness,” she starts. “We are beginning to see traits and facets of personality that suggest a propensity for illness. One of the best described links is between a high neuroticism score and a propensity to develop depression and anxiety disorders. But we also know that people who score low on agreeableness have an increased risk for cardiovascular disease.” As an afterthought she adds “They also die earlier.”

  A little dry in the throat, I mention my own personality test and my own miserably low score on agreeableness.

  “I see,” says Moos Knudsen. She seems undisturbed. “To put it briefly, there is interplay between genes and environmental factors that together determine who we are as people. Our ambition is to understand the intermediate stations found on the way from gene and environment at one end to behavior and personality at the other.”

  One of the intermediate stations she and her team are investigating is the structure of the brain, particularly its intricate chemical communication systems of neurotransmitters, which are exchanged in quick impulses between cells; receptors, which capture and pass on the signals; and hormones, which circulate and provide their own subtle messages. A sloshing ocean of overlapping mechanisms is involved, but the team is especially interested in the actions of serotonin.

  “It is so marvelously versatile,” she says of the neurotransmitter.

  Indubitably. This little molecule is not only significant in the regulation of basic needs such as sleep and appetite but also exercises its effects in more complex matters, including humor, aggression, sexual behavior, and the way we react to punishment and loss. Many of the things that are said t
o color personality. And when I look down at the list of the genes Moos Knudsen has been so kind as to test in me, they are all pieces in the great serotonin system: genes coding for proteins that transport serotonin in tissue, or for a number of different receptors that, each in their own way, convey signals via the same neurotransmitter.

  Take the receptor with the prosaic name of 5-HT1A. It is a big, intricately folded protein, which sits snugly on the surface of cells in almost every structure of the brain and is deeply involved in a broad repertoire of our cognitive abilities. It is also the most widespread of all the serotonin receptors. Scientists know from experiments that, among other things, the 5-HT1A receptor plays a role in both long-term memory and attention, and genetic studies have shown that it is found in many versions, each of which shifts, ever so slightly, the receptor’s function.

  “The most studied variation is the SNP we call rs6295,” Moos Knudsen informs me, as she riffles through her papers. In this variation either a C or a G nucleobase appears in the 5-HTR1A gene in a certain position. The specific nucleobase affects how the receptor reacts to the serotonin swimming around in the brain. So far, scientists have determined that a receptor with the G variant signals less efficiently.

  “People have had ideas that this precise gene variant has significance for various psychiatric illnesses, but the studies have not really been able to conclude anything,” Moos Knudsen mumbles. Then, she finally finds what she is looking for. “Here it is! Your gene test. I can tell you that you have two copies of the C variant.”

  This news is almost cheering. I’d stumbled onto a trailblazing approach to genetic research suggesting that people with two C variants think less rigidly and with less conformity than people with either two G variants or one copy of each. Curiously, the results also highlighted that how gene variants influence behavior depends on the cultural context in which they’ve grown up. The woman who designed the unusual study is the Korean-born Heejung Kim, a psychologist at the University of California, Santa Barbara, and her take on the genetics of personality has prompted the trendy magazine Seed to call her a genuine “revolutionary mind.”

  Her main work is centered on cognitive flexibility in relation to 5-HT1A. Psychologists know that this receptor plays a central role in how well we adjust our mode of thinking in response to our circumstances. Kim’s assumption was that there would be a difference in performance depending on which variant a person carried. The G variant, with its less efficient signal, would provide less flexibility and thus a poorer ability to alter cognitive style, compared to the C variant. If that is the case, those people in every culture who think most traditionally or most in sync with mainstream culture would be likely to be those with the G variant. Kim confirmed this by comparing Koreans with Americans.

  We know from anthropological and psychological studies that there are characteristic differences in thinking and self-image between Eastern and Western cultures. Whereas Eastern cultures are consistently more community-oriented, Western cultures are more individual-oriented. For example, when Korean, Chinese, and Japanese people are asked to describe a picture, they emphasize, for the most part, the background and the totality;Westerners confronted with the same task typically focus on the foreground and the details. Researchers also talk about holistic thinking, prevalent in Eastern cultures, versus analytic thinking, prevalent in Western ones.

  Kim presented a group of Koreans and a group of Americans of various ethnicities with a standardized questionnaire that determines the degree to which a person’s thinking is collectivist or individualist. Then, she tested each individual’s 5-HT1A gene. When the results were compared, Kim’s hypothesis held water. In both cultures, the individuals with two G variants were the most “culturally typical”: those Koreans who thought in the most collectivist ways and those Americans who thought in the most individualistic ways. By contrast, people with two C variants were the least culturally typical. Snugly in the middle were those individuals carrying one of each type of variant.

  “Fascinating,” remarks Gitte Moos Knudsen when I share the study’s findings with her. “Here we see how different cultural patterns can very directly influence how the same gene gets expressed in behavior, right? On the whole, I think the interplay between culture and genes will be a huge theme in future research. It’s enormously exciting.”

  Personally, I’m warming to the idea of my efficient 5-HT1A receptors and I’m just about to entertain Moos Knudsen with how well I think the result fits my own level of mental flexibility. However, she is already scanning down her list. She pauses for an instant before announcing: “Then, there is the gene for BDNF”–the growth factor that makes brain cells divide and form new connections and is therefore a part of attuning how the brain responds to its surroundings.

  You test for two variants. One codes for a protein with the amino acid valine in a certain position, whereas the other codes for methionine, and methionine has the unfortunate effect of reducing the amount of BDNF available for brain cells to bathe in. The methionine variant is rare, as the vast majority of people have two copies of valine. Moos Knudsen reveals that I carry one of each.

  “I just knew it!” It bursts out of me, and she looks somewhat surprised. From my bag, I produce an article that has just been published in Psychoneuroimmunology. In it, a research group from the Hebrew University in Jerusalem describes how women who happen to be equipped with at least one methionine variant of the BDNF gene appear to be worse at handling stress than those with two valine variants.

  The research team asked just under a hundred subjects to act out a job interview to the best of their abilities – but with cameras rolling and spotlights glaring in their faces. Following this ordeal, the subjects had to solve a bunch of mathematical problems. During the process, each had their production of the hormone cortisol (produced in response to stress) measured. Among the men, the production of cortisol – and, thus, the individual’s stress level – rose most for those with two valine variants of the BDNF gene. In contrast , among the women, those who had the greatest stress response were those with one copy of each variant.

  “Interesting that there is a gender difference,” says Moos Knudsen, flipping through the article. “I wonder what the mechanism is?”

  The Israeli team had no credible proposal to answer her question, so we move to another sex difference that is applicable to one of my genes: the gene that codes for the enzyme monoamine oxidase, or MAOA. As you will remember, MAOA breaks down the neurotransmitter serotonin, and variants of the MAOA gene that lower the production of the enzyme have been linked to a person’s higher sensitivity to social pain. Rejection, social isolation, and similar experiences simply activate more powerful negative emotions in those with less efficient MAOA.

  “Everyone used to call it the ‘warrior’ variant, because they were focusing on aggression,” Moos Knudsen observes. “But it looks like men and women express increased sensitivity differently. Men react in a more extroverted way with aggressive behavior, while women tend to turn the reaction inward.”

  Depression, thy name is woman, I think instinctively before asking nicely for my own results. They don’t look so good – I carry two copies of the less efficient variant. Both Mom and Dad delivered.

  AFTER I’VE HAD a microscopic chance to absorb that news, we turn to good old SERT. This gene for the serotonin transporter is probably the most studied gene in psychiatry.

  “The extent to which the short variant produces a particular vulnerability or not is being debated now,” Gitte Moos Knudsen begins. “I believe the current thinking is this: you can have two copies of the short variant and still go through life in an excellent mood without a single depression. But it is a vulnerability variant in the sense that, combined with unfortunate life circumstances, it is not good to have.”

  I wait while she studies her papers.

  “You do have two copies of the short variant,” she says, undisturbed when I throw my pen on the table.

  Of
course. I knew this. I sit there, pondering the genetic fiasco: two short variants, the worst conceivable combination. So, my damned recurring depressions don’t just come from nowhere, I grumble, thinking back to my meeting with Henrik Skovdahl Hansen and his neuroticism index. As if it explains anything, I tell the story about how my family boasts at least three suicides, when I count both sides. Successful suicides, that is. While I’m grumbling on and on about being cheated of the more “robust” gene variants, I notice that Moos Knudsen is smiling wryly.

  “You have to ask yourself what the sensitive variants are good for,” she says then.

  “Good for?” I don’t really follow her point.

  “Take the short version of SERT. If it were really only a disadvantage, why has it survived many millions of years of evolutionary development, and why is it so frequent? Almost one in five Caucasians has two copies, like you. Have you thought what advantages there might be with that variant?”

  Thought and thought, that’s overstating it a bit. But asked directly, I offer up a vague idea about how fragility can make you warier than more thick-skinned people in situations where things might possibly go wrong. It is conceivable, I suggest, that those of us who have our antennae out to sense life’s brutality are also better at reflecting on our impressions of the world. Moos Knudsen nods slowly and asks whether my personality test doesn’t show a high score on the openness dimension. I confirm that it does and am swiftly handed an article.

  In it, Moos Knudsen and her colleagues propose that openness is the dimension linked to cognitive flexibility and a risk of depression. They suggest that short SERT variants pull an individual in the direction of increased sensitivity, but also seem to provide for a less rigid psyche. In fact, the scientists have seen indications of an interesting interplay between the SERT gene and age. Even though research subjects with and without the short variant could point to the same high score on openness, those who possess the short variant appeared more likely to preserve their openness over time, while others slack off on this personality dimension.