BY: Melissa Munn-Chernoff, PhD
DATE: October 19, 2016
Genetics. This term is often used in psychiatry and discussed in the media, yet I have found in my 15+ years of conducting genetics research that many people do not fully understand what it means. Genetics is a special branch of biology that describes how genes control characteristics and behaviors in plants, animals, and humans. This genetic information is passed down from generation to generation and can help us understand why some people have blue rather than brown eyes, as well as why some people develop cancer and, of course, eating disorders. In some cases, like Huntington’s Disease, if you have the risk variant of the gene, you develop the disorder. However, for psychiatric disorders – eating disorders included – genes are NOT destiny. You can have many risk genes for an eating disorder and never develop the illness.
Most scientists who study genetics are as interested in the environment as they are in genetics. In fact, they realize that to understand most illnesses, you have to take both genetic and environmental factors into account. For example, extensive research is exploring how both the environment and genetics (e.g., via the BRCA1 and BRCA2 genes) contribute to risk for developing breast and ovarian cancer. In a series of blog posts over the next few months, CEED faculty will explain the importance of genetic research in eating disorders and psychiatry in general, and discuss the treatment implications of this research. But before we discuss the research findings, we will explain how genetics research is conducted in psychiatry and eating disorders.
One of the first genetic methods used in psychiatry was conducting a family study. Family studies examine whether relatives of individuals with an eating disorder are more likely to have an eating disorder themselves compared with relatives of individuals who do not have an eating disorder. The relatives are often first-degree relatives (i.e., biological parents and siblings), but can also include second-degree relatives (i.e., grandparents, aunts, uncles) and third-degree relatives (e.g., cousins). Even if you discovered that relatives of someone with anorexia nervosa are at increased risk for developing an eating disorder, you would not be able to tease apart whether that was because of genes or environment. Families share both their genetic material and their environments, making it difficult to tease apart which is contributing to the familial pattern.
Twin studies, on the other hand, investigate the resemblance between pairs of identical and fraternal twins to determine the extent to which these familial patterns can be attributed to genetic or environmental effects. Twin studies are a clever natural experiment because identical twins are functionally genetic clones (they share 100% of their genetic material) and fraternal twins are no more genetically similar than non-twin siblings, but they share more of an environment than non-twin siblings because they were in the womb together and grew up at the same time. Twin studies allow us to identify three contributions to the familial pattern: additive genetic factors (i.e., heritability), shared environmental factors (i.e., environments that both twins experience and make them more similar), and individual-specific environmental factors (i.e., environments that only one twin experiences that make them less similar). Twin studies are great for telling us how heritable a disorder is, but they are unable to identify specific genes that increase risk for a disorder.
Linkage studies were one of the first methods that allowed for assessing which genes may be involved in the risk for eating disorders. These studies identified families, some over multiple generations, in which many people had eating disorders in an effort to identify regions of the genome that are shared between family members who have the illness. Linkage studies have fallen out of favor as they have not been very fruitful in psychiatry. Candidate gene studies dominated the literature for a while and they explored the association between a particular gene or genes and a disorder. In these studies, the researcher had to make an educated guess about the biology of an illness and develop a specific hypotheses as to why it may have biological relevance to the disorder. We spent a lot of time doing candidate gene studies, but most often, discoveries were followed by several failed attempts, meaning that other groups could not replicate what the first group found. Replication is essential in science so that you know your finding is real and not just chance. The psychiatry field welcomed the arrival of genome-wide association studies or GWAS, as they are commonly referred to. GWAS are discovery science. That means that you do not have to go into a study with any prior knowledge about a gene or any biological hypotheses about why a gene may be associated with eating disorders. You can just let the genome speak for itself. GWAS scan the entire genome for over 1 million genetic markers and compare the genomes of thousands, tens of thousands, and even hundreds of thousands of cases to the genomes of as many controls. Even though it is a massive undertaking to collect such large samples of individuals, GWAS are the preferred method for examining the genetic underpinnings of psychiatric disorders. Unlike family and twin studies, GWAS allow us to identify risk genes for disorders. We expect that there will be hundreds of genes that contribute to risk for eating disorders, so there is a lot of work to do. But ultimately, we hope that unraveling the genetic code will allow us not only to identify genes that increase risk, but that they will also allow us to better understand why some people are more vulnerable to environmental risk factors than others.
As we move forward with this series of blog posts on genetics and eating disorders, we hope it will be clear that these methods are only small pieces of the puzzle in unraveling the complex risk for eating disorders. At CEED and with our partners around the world, especially at Karolinska Institutet in Sweden, we are dedicated to the balanced investigation of both genetic and environmental risk factors. As you will see, we are applying multiple methods to unlock these mysteries, all in the service of understanding the biology of eating disorders and ultimately, improving our ability to personalize and optimize both prevention and treatment.