Wednesday November 21 2012
Previous research has shown the FTO gene may be linked to obesity
'Fat people really are more jolly,' is the Daily Mail's childishly over-simplistic take on a complex piece of research that looks at the association between BMI, depression and a specific genetic variant called FTO.
The FTO gene has already been linked to obesity. Researchers were interested to see if certain variants of the gene could have an impact on the risk of developing major depression.
The headline 'fat people really are more jolly' bears little resemblance to the research it is based on and is actually the opposite of the study's findings. The researchers examined whether the FTO gene variant protected against major depression, irrespective of BMI. They also looked at the risk of being diagnosed with depression, not at whether a person was happy or 'jolly'. There are plenty of overweight people who, while not clinically depressed, could never be described as jolly.
The study also found the increase in the risk of developing major depression was quite small, at an 8% greater risk for each copy of the genetic variant. It is not clear whether all overweight people have this genetic trait, as the Mail headline implies.
Overall, the single genetic variant examined in this study is highly unlikely to provide the whole answer to:
- why people are the weight they are, which is greatly influenced by diet and physical activity levels
- why people suffer from depression, which may be influenced by many factors such as life and health circumstances
Where did the story come from?
The study was carried out by an international collaboration of researchers from various academic and medical institutions. It was funded by the Canadian New Investigator Fund from Hamilton Health Sciences and the Canada Research Chairs programme.
The research was published in the peer-reviewed science journal, Molecular Psychiatry.
The Daily Mail's headline 'fat people really are more jolly' is misleading and does not reflect the underlying research, reporting the opposite of what the study concluded.
The researchers actually found that for most people, an increase in BMI led to a modest increase in the risk of depression of 2% for each BMI point.
The Mail's reporting of the study provided little more than a good opportunity to publish a picture of Strictly Come Dancing favourite Lisa Riley, but they wouldn't have scored a perfect 10 for their coverage.
What kind of research was this?
This was a cross-sectional genetics study looking at whether variants of a gene previously associated with obesity (the FTO gene) were linked to depression.
The gene has previously been linked to obesity. The authors also report that this gene is highly active in brain tissue and that certain variants of the FTO gene variant investigated in this study (FTO rs9939609 A) are linked to conditions such as reduced verbal fluency, or difficulty finding words.
The high level of activity of the gene in the brain led the authors to speculate that it may also be involved in psychological conditions such as depression. Their study aimed to explore this link.
Mental health conditions such as depression often have multiple complex genetic and environmental causes. Identifying individual genes associated with different conditions helps scientists better understand diseases and explore ways to treat them.
However, discovering a gene is linked to a condition such as depression, which may have complex underlying causes, does not necessarily mean it is an important factor in causing the disease. This only means that there is an association between the two, not a direct cause and effect relationship.
What did the research involve?
This study pooled genetic and demographic information (age, ethnicity, BMI) from four existing studies that had recruited diverse ethnic populations:
- EpiDREAM study
- INTERHEART study
- a depression case-control study
- CoLaus study
It also gathered data on clinical diagnoses of major depression, defined according to DSM-IV diagnostic criteria (a widely-used measure).
The pooled sample included a total of 6,561 cases of depression and 21,932 controls (without depression). Demographic and genetic data was obtained from each of the four studies in different but standard ways. For example, DNA was extracted from blood cells in one study cohort and from blood or epithelial cells in another.
People have multiple copies of different genes, so once the data was pooled researchers tested whether there was a link between the number of copies of variations of the FTO gene and a diagnosis of depression.
The statistical analysis was appropriate and took into account other factors that influence depression and a person's genetics, such as body mass index (BMI) and ethnicity.
What were the basic results?
A meta-analysis pooled the results of all four studies, which included 6,561 cases of depression and 21,932 people without depression (controls).
The meta-analysis found a significant association between the obesity gene variant (FTO rs9939609 A) and depression. It showed that each copy of the genetic variant was associated with an 8% reduction in the risk of depression (odds ratio (OR) 0.92 95% confidence interval (CI) 0.89-0.97).
This finding was independent of variations in age, sex, ethnicity and population structure, and body mass index (BMI).
No significant variation was found between the results from the different studies, despite having different inclusion criteria and ethnic compositions.
Differences in ethnicity only had a limited effect on the link between the FTO variant on the risk of depression.
The same variant (FTO rs9939609 A) was also associated with increased BMI in the four studies. This showed that every copy of the genetic variant contributed to a 0.30 unit increase in BMI (β=0.30 95% CI 0.08-0.51). This was independent of variations in age, ethnicity and population structure, and sex.
Interestingly, in the only study that reported it (EpiDREAM) a higher BMI was also associated with higher levels of depression. Each unit increase in BMI increased the risk of depression by 2% (OR 1.02 95% CI 1.02-1.03).
How did the researchers interpret the results?
The authors concluded that they "provide the first evidence that the FTO rs9939609 A variant may be associated with a lower risk of depression independently of its effect on BMI. This study highlights the potential importance of obesity predisposing genes on depression."
They point out that, "Our data suggest that FTO may have a broader role than initially thought, and may not only regulate energy balance and body weight but also have a direct impact on cognitive function and psychiatric disorders."
They also warn that, "The observation that FTO rs9939609 A variant is associated with a higher BMI but a lower risk of depression is unexpected, and thus our result must be interpreted with caution."
This study found a significant association between the genetic variant FTO rs9939609 A and the risk of diagnosed depression, independent of BMI.
The relative increase in the risk of depression was small, at an 8% greater risk for each copy of the genetic variant.
It was also not clear from the study how common this genetic variant is among the general population and how many people may be affected by this finding.
The study had a number of strengths, including a large sample size, consistent findings across four different studies (including multiple ethnic groups) and consistent diagnostic criteria for depression.
However, there are also important limitations to consider. For instance, the four studies included in the analysis selected individuals to participate in their studies based on different criteria, including:
- their risk of developing diabetes
- whether or not they had suffered a heart attack
- those with recurrent depression
- 'healthy' people from the general population
Due to the combined nature of the results, it is not clear who the results are most applicable to and whether they can be applied to the general population as a whole or specific groups at risk of certain diseases.
In addition, we cannot totally exclude the possibility that unknown confounding factors may explain the association between the genetic link and depression, as the relationship is likely to be complex.
The conclusion of the study authors that, "The FTO gene may have a broader role than initially thought, with an effect on depression and other common psychiatric disorders" seems valid. Further research is needed to confirm or refute this proposed link and explore other influencing factors.
Both depression and obesity are complex conditions that are thought to arise from a combination of factors such as environment, societal pressure, genetics, individual life history, diet and physical activity levels.
Claiming that there is such a thing as a single 'fat gene' or 'jolly gene' is overly simplistic.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on twitter.