Where’s the Bipolar Gene?
Given all the activity and advances in genetic research, you might expect researchers to have mapped the entire human genome by now and identified the gene or genes responsible for bipolar disorder and other diseases that appear to have a genetic component. Obviously, that hasn’t happened. The best that researchers seem to have come up with are associations of certain gene variations with bipolar – hardly the smoking gun we would hope for.
Even the researchers seem to be getting a little discouraged, as is evident in a two articles I have recently come across. The first, published in the April 2011 edition of the American Journal of Psychiatry is entitled “After GWAS: Searching for Genetic Risk for Schizophrenia and Bipolar Disorder,” (by Elliot S. Gershon, Ney Alliey-Rodriguez, and Chunyu Liu). In their abstract, the authors explain:
Ten years ago it was widely expected that the genetic basis of common disease would be resolved by genome-wide association studies (GWAS), large-scale studies in which the entire genome is covered by genetic markers. However, the bulk of heritable variance remains unexplained.
In the April 2011 edition of Molecular Psychiatry, a perspective entitled “The missing genes: What happened to the heritability of psychiatric disorders?” reinforces the notion that a clear genetic link to bipolar disorder and other psychiatric illnesses continues to elude researchers’ best efforts:
Less than 2% of the 80–90% heritability of major psychiatric disease, for example, schizophrenia and manic-depressive illness is attributable to genes identified by linkage and association. Where is the missing heritability?
The inability to identify a clear genetic link to bipolar disorder doesn’t mean that such a link is missing. It only means that identification of such a link is more challenging than researchers had hoped. The authors of these two articles suggest various reasons why the genetic link is so elusive, including the following:
- Multiple variants have a cumulative effect of making an individual more susceptible to a given disease. In other words, rarely does a single gene or variation result in increasing an individual’s risk of developing the disease.
- Genome-wide association studies (GWAS) produce too much “noise” that may hide valid gene-illness links. Researchers are considering parsing (breaking down) the genome to study smaller subsets of data.
- Even large-scale studies are too small to completely identify all genetic variants. With technological advances and declining costs, researchers may be able to expand genome-wide sequencing studies for more comprehensive data.
- Epigenetics (differences in how a gene expresses itself) may cloak any genetic link. In other words, a particular gene may or may not increase the risk of bipolar disorder depending on the way that gene is expressed in an individual. (For more about epigenetics and bipolar disorder, see our previous post, “The Effects of Chronic Stress on Bipolar Genes.”
Reading these comments from researchers can be a bit deflating – the excitement about identifying the genes that cause bipolar disorder seems to be losing some steam in the face of the complexity of the process, technical limitations, and costs of the necessary research techniques. But I think it’s way too early to be discouraged.
Like all scientific exploration, this process often ends up opening up more doors and asking more questions than it answers, at least in its initial stages – that’s the nature of research. It’s always more complicated and expensive than we anticipate.
Even before understanding the genetics of brain variations such as mental illness, studies of typical brain development and behavior have shown that there are few linear or straightforward connections between singe genes and behavior or emotions. The old genetics we learned in high school about peas and eye color don’t work in this area. We have only just begun this journey to understand the science of ourselves.
I am confident that ongoing research will ultimately provide us with valuable information about people at risk for mental illness and the how environmental factors act upon these genetically based vulnerabilities. In the longer term, we will know significantly more about the evolution of these conditions and maybe even how to reduce risk of developing full blown conditions. In a more short-term way, the genetic work helps scientists identify more specific molecular pathways related to illness, even if these are not simple cause-and-effect relationships, that point us toward new and hopefully more targeted and effective treatments strategies.
This is really difficult work, and it seems understandable that those on the front lines might get discouraged with slow progress in their fields. Thank goodness for these brilliant scientists who have set out to do this extremely difficult work – they are the reason we have made such enormous gains, and they bring us hope for more successful care for our patients in the future.
Photo by Daniel D, available under a Creative Commons attribution license.
Fink, C. (2011). Where’s the Bipolar Gene?. Psych Central. Retrieved on September 4, 2015, from http://blogs.psychcentral.com/bipolar/2011/03/bipolar-disorder-gene/