Francis J. McMahon talks with
ScienceWatch.com and answers a few questions about
this month's New Hot Paper in the field of Neuroscience
& Behavior.
Article Title: A genome-wide association study
implicates diacylglycerol kinase eta (DGKH) and several
other genes in the etiology of bipolar
disorder
Authors: Baum, AE, et al.
Journal: MOL PSYCHIATR, Volume: 13, Issue: 2, Page:
197-207, Year: FEB 2008
* NIMH, Unit Genet Basis Mood & Anxiety Disorders, Mood
& Anxiety Disorders Program, US Dept HHS,NIH, 35
Convent Dr,1A-202, Bethesda, MD 20892 USA.
* NIMH, Unit Genet Basis Mood & Anxiety Disorders, Mood
& Anxiety Disorders Program, US Dept HHS,NIH, Bethesda,
MD 20892 USA.
(addresses have been truncated)
Why do you think your paper is highly
cited?
This is the first genome-wide association study (GWAS) published on bipolar
disorder, a common mental illness of unknown etiology. GWASs command
attention due to the relatively comprehensive picture they can give of the
genetic architecture of a trait.
Does it describe a new discovery,
methodology, or synthesis of knowledge?
We used a relatively novel DNA pooling strategy that cut the costs of the
study about 30-fold, compared to individually genotyping each sample on a
genome-wide array. While it has limitations, this may be a promising
approach for initial genome-wide screening to see whether a trait is worth
the significant investment of individually genotyping thousands of subjects
on genome-wide arrays.
Would you summarize the significance of your
paper in layman's terms?
There are three main points. These are: 1) Even though bipolar disorder is
inherited, there seem to be no common gene forms (alleles) that have a big
impact on the risk for this condition. 2) One gene, DGKH, seems to play a
role. This gene participates in a biochemical pathway that is known to be
affected by lithium, a key medication for bipolar disorder (Figure 1). 3)
Many genes seem to play a role in disease risk, and only people who have
inherited a lot of these genes have a high risk of bipolar disorder (Figure
2). The "tipping point" at which someone was equally likely to have bipolar
disorder or not, occurred at about 15 risk alleles in our study, but since
we did not detect all relevant genes, this is probably an underestimate.
How did you become involved in this research,
and were there any problems along the way?
I have been studying bipolar disorder for over 15 years. I have always
found it intriguing that a disorder that manifests itself only in the mind
can nevertheless be so strongly inherited. Despite this fact, progress in
identifying the actual genes involved has been very slow. We now recognize
that this probably reflects the role of many different genes in determining
disease risk.
Where do you see your research leading in the
future?
We hope that studies like ours will lead to a better understanding of the
biological basis of bipolar disorder—which is still largely
mysterious—so that better methods of diagnosis and treatment can be
developed.
Do you foresee any social or political
implications for your research?
Our research implies that genetic tests will have little or no role in the
diagnosis of bipolar disorder for the foreseeable future. There are just
too many genes involved, and the magnitude of risk conferred by any one
gene is just too small.
Francis J. McMahon, MD Chief, Genetic Basis of Mood and Anxiety Disorders National Institute of Mental Health National Institutes of Health Bethesda, MD, USA Web