RETURN TO TABLE OF CONTENTS
Winter 2002

Twins Study Looks For Genetic Link

Research holds the key to conquering chronic fatigue and immune dysfunction syndrome (CFIDS). Experts are testing a vast number of theories about what causes CFIDS, from viral agents to hormone imbalances to neurological irregularities. At the same time, they're looking at drugs and other treatments that could ease symptoms or even reverse the course of CFIDS.
 
The Chronicle will devote 2002 to exploring the state of some of these research efforts. This is the first in a periodic series of question-and-answer sessions with leading CFIDS researchers.

Is CFIDS a disease of genetics or environment? Researchers at the University of Washington are trying to answer this key question by studying an unusual group of human subjects: twins.

The university's Chronic Fatigue Syndrome Cooperative Research Center is testing hundreds of twin pairs to learn how genes may influence the development of CFIDS. The Chronicle asked center researcher and Associate Director Niloofar Afari, PhD, to explain what's been discovered so far - and what may lie ahead.

Q: Why study twins?

A: Twins are very important because of who they are. Monozygotic, or identical, twins share all of their genetic materials. Dizygotic twins, also known as fraternal or non-identical twins, share on average about half of their genetic material. This is important because it helps distinguish between the genetic and the environmental causes of illnesses.

Say you study two people with the same genetic material. If one of them has a disease or shows certain test results and the other one does not, you can figure that there may be environmental factors at play. We're trying to apply those research strategies to chronic fatigue syndrome (CFS), to look for possible biological and environmental causes.

Q: How do you conduct your research?

A: We have several things going on. We started established in 1996. It's a volunteer registry. We have put out the word to twins organizations, CFS organizations and physicians who treat people with CFS or fibromyalgia (FM). We're interested in twins where either one or both have chronic fatigue, CFS or FM.

Right now the registry is probably close to 250 pairs. We have the whole gamut of twins, monozygotic and dizygotic, including some opposite-sex pairs. Some are discordant, meaning that one twin has chronic fatigue, CFS or FM and one twin doesn't. Others are concordant, meaning they both have one of these conditions.

We've collected a huge number of measures on participants in this registry. The booklet of questionnaires that we send out to them is about an inch thick. It has a medical history to fill out, including symptoms of fatigue and other problems.  The twins keep a sleep diary, which lasts for two weeks, where they record information about their sleep patterns.  There's a whole battery of other measures about stress, coping, family disease history and social support, general levels of pain and fatigue, personality, social support, any kind of threatening life experiences they've had -- you name it, we ask it.

We also use the registry to pinpoint a group of monozygotic, discordant twins to do more comprehensive evaluations. That's what we call the intensive study. We are in the second round of these intensive studies. For the first intensive study, we brought in 21 pairs of discordant monozygotic twins from all over the country to Seattle. We did a week-long battery of tests. Again, you name it, we did it. Everything from psychiatric interview to a three-night sleep study, exercise testing, blood draws, hormonal levels. We tried to cover tests that would relate to all the theories about the causes of CFS.

For the second round, we're bringing in as many of those twin pairs as possible and doing follow-up testing. The tests are along slightly different lines, because we're looking for slightly different things. But again, we're doing exercise testing, sleep studies, brain imaging, psychiatric evaluations. This will help us get some longitudinal information, to see how things may change over time.

Q: What have you learned from the registry?

A: When we're looking at the discordant pairs, we have some interesting but unanticipated findings.   For example, there don't appear to be huge differences in how the twins cope with things in their lives. There are some differences, like the use of a few particular coping strategies, but certainly not as big as we might have expected.

Q: How about the first intensive study?

A: Again we have some interesting but unanticipated findings.  Mainly, we have found that with our sample of discordant identical twins, both members of the pair show similar abnormal findings on a number of tests. For example, in exercise testing, they both appear to be doing similarly -- but similarly poorly. So even though we are not finding huge differences between the CFS and non-CFS twins, we have some intriguing results that we are now exploring in more detail.

You can learn a lot from the test results. If they do show a difference, you can attribute that to what's different about the twins, which is their environment. If they don't show a difference, you can attribute that to what's the same - their genetics.

Basically, when we've not been able to show too many differences -- such as with the poor exercise results - that means that there's quite possibly a hereditary component to chronic fatigue.

Q: Can you definitely say there's a genetic component to CFS?

A: No, I don't think we're there yet. At this point, I would say that things are pointing in the direction of genetics, but I couldn't say right now that there's some genetic cause. We're pretty early on in this line of research.

Also, as is the case with many other illnesses, CFS is likely the result of  both genetics and the environment.  That's what we call the gene by environment interaction.

Q: What are you looking for now?

A: In the previous round, we found evidence that the twins are not so different from each other, but yet abnormal in many of their findings. In this round, we are looking more closely using ever more precise assessments to identify the underlying mechanisms for CFS.  That is, we're looking for why one of them would exhibit symptoms while one won't. For example, one of the things we're focusing on is perception. The question is how the twin with CFS perceives things differently than the person without CFS.

Perception could be seen as something that is biologically or genetically driven. Two people could have exactly the same experience, yet the body systems of one would sense it, perceive it, differently than those of the other person. This is important: By studying perception, we don't mean that it's all in your head. It doesn't mean that you think you have CFS and therefore you do. It means that the bodies of people with CFS may sense things differently. These differences could become diagnostic markers for CFS.

For example: One of the studies we're doing is pain testing. We're trying to establish the twins' pain thresholds. At what point do they experience pain, and at what point do they perceive the pain to be intolerable?

There's no doubt that people feel pain. You give them a strong enough stimulus, they're going to say "ouch." But at what point does somebody say "ouch"? That's perception.  We want to know at what point the systems of a CFS twin says "ouch," and whether that's different than with the non-CFS twin. That could be a diagnostic marker for CFS.

It's the same with fatigue. We would test this by putting someone on an exercise bike. You ask them to keep going to see at what point their bodies say, "I'm pretty tired," and what point they say, "I'm so exhausted I can't go on any more."

We don't know what we're going to find. But once we gather the data, we'll start looking at how to apply it. We're supposed to be finished with this by 2004. Then we'll get ready for the next round of studies.

The research center is interested in enrolling more twin pairs for its registry. One or both of the twins must have CFS or FM. Contact Megan Belcourt at 206-521-1935, or call toll free at 1-888-223-0868 and ask for Megan.