- The Washington Times - Wednesday, January 19, 2005

Although some people consider twins to be double trouble, the duos actually are a double benefit to genetic research, says Lindon Eaves, distinguished professor of human genetics and psychiatry at Virginia Commonwealth University in Richmond.

“We can’t manipulate the genes or the environment in humans so what we have to look for is a natural experiment,” says Mr. Eaves, who holds a doctorate in genetics. “They come in two kinds, identical twins and nonidentical twins.”

Most researchers agree that genetics influence many behaviors to some degree. Twins studies, which have been going on for decades, continue to help define the specific ways genes can affect behavior.

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Generally, researchers contrast fraternal or nonidentical twins, who develop from two eggs fertilized by different sperm, with identical twins, who develop from one fertilized egg that divides into two babies.

“You expect identical twins to be more similar than nonidentical twins,” Mr. Eaves says. “If you can measure the similarity on that kind of a scale, a comparison of degrees of similarity gives an estimate of the strength of genetic influence.”

The extent to which identical twins don’t have identical behavior reveals how the environment has shaped the individuals, Mr. Eaves says. He has studied 1,400 families of twins who were located about 15 years ago through the Virginia school systems.

The families were followed for 12 years, focusing on the role genes play in adolescent behavior and young adult life. Adolescent depression, anxiety disorders, attention deficit hyperactivity disorder, conduct disorder, substance abuse and oppositional defiant disorder are among the problems considered in the study.

“We have a very strong sense that you can’t ignore the genes in complex behavior, but we’re a long way away from saying, ‘These are the particular genes that influence particular things,’” Mr. Eaves says. “If you can really pin down one or two genes that have a clear-cut influence on the outcome, you could begin to look at how the genes affect the outcome and give better drug treatment.”

Investigating adult samples of twins is equally as important as studying adolescents, says Dr. Kenneth Kendler, professor of psychiatry and human genetics at Virginia Commonwealth University. He has focused his work on psychiatric and drug abuse disorders in adults. Since the 1980s, he has conducted a set of related studies with 6,000 twins.

The results of Dr. Kendler’s studies show genetic factors are 25 to 50 percent of the cause for many psychiatric disorders, and about 60 percent of the cause for drug abuse and dependence, he says. Environmental factors are the remaining risk factors.

“We’ve found the impact of stressful life events on depression is moderated by the effects of genes,” Dr. Kendler says. “If you’re predisposed to depression, stressful life events could ‘turn on’ the genes. Genes moderate the way you respond to stress. We all know that people differ in response to stress.”

Different responses to stress aren’t the only reactions that vary from person to person. For instance, Scandinavians with the variant gene for addiction to morphine or opiates are more susceptible to becoming addicted than other Scandinavians, according to research by professor Mary Jeanne Kreek at Rockefeller University in New York City, says Jonathan Pollock, chief of the genetics and molecular neurobiology research branch at the National Institute on Drug Abuse in Rockville. Mr. Pollock holds a doctorate in physiology and neurobiology.

Since researchers now know that the morphine receptor can be altered, that receptor is a potential target for treatment, he says. A receptor is a site on a cell where chemicals bind to activate or inhibit cellular functions. More research is needed, however, to show if the variant gene is the only reason for the addictions.

In the future, Mr. Pollock imagines a test might be available to determine the probability of illness occurring in a person, due to genes. Some genetic tests already exist, such as those predicting the risk of developing breast cancer. Therefore, better treatments and precautions could be taken with environmental factors.

The development of the nervous system is shaped both by genes and by the environment, he says.

“People like to put it as ‘either/or,’ and it’s not, and I think people want to be in control,” Mr. Pollock says. “People can control in some extent their environment. They can’t quite control their genes. They like to think that what’s happening to them is a result of external factors, but it’s both. Some people also take solace that there’s certain things that they can’t control.”

In addition to twins, many researchers have begun to study siblings, to build a larger sample, says Irving Gottesman, professor of adult psychiatry at the University of Minnesota Medical School in Minneapolis, who holds a doctorate in clinical psychology.

The more people researchers study, the easier it is to detect subtle effects of genes, he says.

“Siblings are only the same in their genetic level in about half of their genes,” Mr. Gottesman says. “If you and your sister don’t resemble each other at all, then you have fewer than 50 percent of your genes in common. It’s just the way the ball bounces and how the genes are formed at conception.”

He hopes to differentiate the single nucleotide polymorphisms, or SNPs, in healthy siblings versus sick siblings. An SNP is a single change in a gene’s DNA sequence.

“The person who has an illness, such as bipolar disorder, has different SNPs than his or her sibling that doesn’t have [the disorder],” Mr. Gottesman says. “If you do that in enough pairs, you build the credibility of it being a real finding. … Then we can identify the SNPs to a particular gene.”

With most cases of genetic influence, illness is probably caused by multiple genes, says Dr. Elliot Gershon, professor of psychiatry and human genetics at the University of Chicago.

Researchers have identified that multiple genes cause bipolar disorders, schizophrenia and autism, he says. In fact, schizophrenia and bipolar disorder appear to share some of the same genes.

Although today’s twins studies are being used to research people’s health, it concerns Dr. Gershon that genetics has been associated with racism in the past, he says. Now, the association between behavior disorders and genetics is gaining credibility, he says.

In 2001, Peter McGuffin, Brien Riley and Robert Plomin published an article in Science magazine saying there is a substantial genetic component to such things as IQ in both adulthood and childhood, reading disabilities, personalities, major depression, autism and attention deficit hyperactivity disorder.

“This gives us a lot of hope,” Dr. Gershon says. “There have been repeatable discoveries that genes are associated with illnesses.”

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