The methodological confusion of twin studies.

A couple of things.
Aug. 24 2011 3:17 AM

Double Inanity

Twin studies are pretty much useless.

Twins. Click image to expand.
How reliable is studying twins?

One of the main messages of science over the last couple of decades is that genes are destiny. With every new issue of a psychology journal, it seems that the portion of your life governed purely by your own free will gets smaller and smaller. Genes determine 50 percent of the likelihood that you will vote. Half of your altruism. One-quarter of y our financial decisions.

How do we know? Twin studies. Researchers compare some behavior or trait in a set of pairs of monozygotic (identical) twins and a set of pairs of dizygotic (fraternal) twins. In theory, the siblings in each pair have been raised in the same way—i.e., they have "nurture" in common. But their "natures" might be different: Identical twins come from the same sperm and egg and are assumed to share their entire genomes; fraternal twins match up at only about half their genes. So if the pairs of monozygotic twins tend to share a trait more often than the pairs of dizygotic twins—be it the likelihood they will vote, a tendency toward altruism, or a strategy for managing their financial portfolios—the difference can be chalked up to genetics.

Some call this approach beautiful in its simplicity, but critics say it's crude, potentially misleading, and based on an antiquated view of genetics. The implications of the studies are also just a little bit dangerous, because they suggest, for example, that some people just aren't cut out for being nice to one another.

The idea of using twins to study the heritability of traits was the brainchild of the 19th-century British intellectual Sir Francis Galton. He's not exactly the progenitor you might want for your scientific methods. Galton coined the term "eugenics" and was the inspiration for the push to manipulate human evolution through selective breeding. The movement eventually gave us forced sterilization and the most offensive passage in the history of the U.S. Supreme Court (and that's really saying something): "Three generations of imbeciles are enough."

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Galton's seminal 1875 study of twins was designed to prove that England's "chief men of genius" were the product more of good breeding than of good rearing. Based on the incredible similarities he found between twins in 80 questionnaires, Galton trumpeted his conclusion to the world that nature soundly beats nurture. By modern standards, though, Galton's methodology was only good enough for cocktail conversation. His sample was too small, his subjects were all upper-class, and, since he didn't understand the difference between monozygotic and dizygotic twins, Galton had no control group. (To his credit, he acknowledged this limitation, even though it didn't get in the way of his sweeping claims.)

Nearly five decades after Galton published "The History of Twins"—and more than 10 years after the word "gene" entered the lexicon—researchers in the 1920s "perfected" Galton's methods by comparing identical and fraternal twins and inferring heritability from the differences between the two. The twin study today is based on the same assumptions that were made back then. (As you may be aware, a lot has changed in the field of genetics over that time.) And despite numerous indications that these assumptions are deeply flawed, researchers continue to crank out new papers, probably in response to a public demand—both insatiable and inexplicable—for evidence that we're just like our parents. (If only Freud were alive today.)

Consider a 2005 study by Rice University's John Alford and his colleagues claiming to show that 43 percent of the variation in political ideology in the U.S. could be attributed to genetics (PDF). With surprising precision, the authors listed several political issues, and the degree to which the public's views on each were shaped by genetics. They concluded that genetic predetermination could explain the "otherwise puzzling consistency in ideological divisions that is present across space and time."

Pause for a moment to examine that astonishing claim—that Americans' stubborn insistence on disagreeing over hot-button national issues is the result neither of two parties adjusting their views to appeal to a shifting political center nor of the fact that the issues on which we have learned to agree simply fall out of the political debate. (How many slavery proponents do you know? I hear there used to be a few of them in the U.S. Senate.) Nope. It has to be the series of base pairs in our cellular nuclei.

Fortunately for the future of our democracy, the study's conclusions far outpace its evidence. Three years after the Alford study came out, a Duke political scientist named Evan Charney (PDF) and Harvard geneticists Jon Beckwith and Corey Morris examined the flaws in the Alford study—and showed why all the other twin studies on heritability can't possibly show what they purport to show.

Twin studies rest on two fundamental assumptions: 1) Monozygotic twins are genetically identical, and 2) the world treats monozygotic and dizygotic twins equivalently (the so-called "equal environments assumption"). The first is demonstrably and absolutely untrue, while the second has never been proven.

That identical twins do not, in fact, have identical DNA has been known for some time. The most well-studied difference between monozygotic twins derives from a genetic phenomenon known as copy number variations. Certain, lengthy strands of nucleotides appear more than once in the genome, and the frequency of these repetitions can vary from one twin to another. By some estimates, copy number variations compose nearly 30 percent of a person's genetic code.

These repeats matter. More than 40 percent of the known copy number variations involve genes that affect human development, and there are strong indications they explain observed differences between monozygotic twins. For example, it's often the case that one identical twin will end up victimized by a genetically based disease like Parkinson's while the other does not. This is probably the result of variations in the number of copies of a certain piece of DNA. Copy number variations are also thought to play a role in autism spectrum disorder, schizophrenia, and ADHD, all of which can appear in only one member of a monozygotic twin pair (PDF). If copy number variations can affect discrete and diagnosable disorders, then why shouldn't they influence far more complex behaviors like your inclination to head to the polls on a Tuesday night in November?

That's just the beginning of the genetic differences between monozygotic twins. As a result of mutations during development, about one in 10 human brain cells has more or less than the typical two copies of a chromosome. Identical twins also have different mitochondrial DNA, the genetic information stored in the cellar organelle responsible for processing glucose. Research suggests that mitochondrial DNA affects brain size among a host of other neurological traits.

Twin studies also rely on the false assumption that genetics are constant throughout one's lifetime. Mutations and environmental factors cause measurable changes to the genome as life progresses. Charney cites the example of exercise, which can accelerate the formation of new neurons and potentially increase genetic variation among individual brain cells. By the time a pair of twins reaches middle age, it's very difficult to make any assumptions whatsoever about the similarity of their genes.

The equal environments assumption is similarly questionable. As anyone who's ever seen a pair of toddler twins in matching sailor suits is surely aware, monozygotic twins do get special treatment. They are more likely than their dizygotic peers to be treated as "two of a kind" by family, friends, and teachers, which must increase their chances of developing similar behaviors. There have been numerous studies showing that dizygotic twins who look similar have more personality traits in common than those who are easily distinguishable.

In addition, genetics and environment aren't separable elements, so any attempt to discern their independent contributions to an observed trait is foolish. The epigenome, the part of our genetic makeup that determines when genes are transcribed—that is, when they actually become relevant to our existence—is deeply affected by conditions in the womb and the unquantifiable complexity of the external environment.

Our knowledge of the human genome is far too superficial for anyone to be making percentage estimates of the extent to which our biology sets our destiny. Consider the unfortunate story of the Texas rancher who cloned his beloved, sweet-natured bull only to find that the new model was the polar opposite in temperament. The clone gored his master repeatedly, dislocated his shoulder, ripped open his scrotum, and fractured his spine.

Duke's Evan Charney likes to compare off-the-shelf twin studies of human behavior to phrenology, the 19th-century pseudoscience that attempted to link intellectual capacity to skull size and shape. He may have something. There's a strong temptation to believe that the same genes that make identical twins look so similar also make them think and act identically. That assumption isn't just insulting to a twins' individuality; it displays a reductive attitude toward the incredible complexity of our genetic structure, which scientists are just beginning to understand.

None of this is to say that genetics don't play some role in our behavior—they absolutely must. But twin studies are a fundamentally flawed method for quantifying that influence. Don't believe for a second that anyone can put a percentage estimate on your genetic inclination toward altruism by asking a few questions to a bunch of twins.

Brian Palmer writes about science, medicine, and the environment for Slate and Earthwire. Email him at explainerbrian@gmail.com. Follow him on Twitter.