Tuesday , January 25 2022

Genetic links between depression and obesity explored


"Genetic variants linked to high BMI can lead to mental health issues," reports The Guardian.

Depression is more common among people who are obese. But previous studies have not been able to determine whether there is a direct cause and effect relationship. So it could be the case that depression causes weight gain rather than the other way around, or indeed both could be true.

Also, it could be the complications associated with obesity, such as type 2 diabetes, contributing to depression rather than the obesity itself.

This latest study attempts to use a genetic technique to focus on the effects of obesity on depression and other lifestyle and health factors. The researchers looked at the DNA of a half million adults with white European ancestry in the UK.

The researchers looked at 73 genetic variations which had previously been linked to higher BMI. Some of these have also been linked to a reduction in risk of metabolic complications such as high cholesterol or blood sugar levels.

The researchers found that a combination of the genetic variants was associated with higher BMI. This was a testimony to the fact that it was even the case when a person had the variants of their metabolic complications. This may suggest that obesity influences depression risk psychological rather than metabolic changes; at least in some cases.

We can not change our DNA, taking regular exercise and eating. Read more about how you can improve your mood and improve your health.

Where did the story come from?

The University of South Australia Cancer Research Institute and King's College London.

The researchers were funded by the Australian Research Training Program, the UK Medical Research Council, the Wellcome Trust, the European Research Council, the Royal Society, the Gillings Family Foundation, Diabetes UK, the National Institute for Health Research (NIHR) Biomedical Research Center, Maudsley NHS Foundation Trust and King's College London. The study was published in the peer-reviewed International Journal of Epidemiology on an open access basis.

The Guardian reported the study accurately, including a mention of the limitations. The Mail Online has provided the sketchy details of the study, skirting over the genetic analysis and concluding that the psychological impact of being overweight increases the risk of depression, when this was only suggested by the results and not proven.

What kind of research was this?

This was a case-control study, comparing the genetic makeup of people with and without depression.

Depression is more common among people who are obese. However, it is not true whether there is a risk of depression, whether it is true or not.

So researchers carried out a particular type of case-control study known as a Mendelian randomisation study, where researchers focused on the genes associated with disease risk and health outcomes rather than lifestyle factors.

The idea behind this type of study is the exact combination of DNA that people inherit from their parents is random. So the analysis reduces the possibility that other factors (confounders) are causing the link between obesity and depression.

What did the research involved?

The researchers used genetic information from about 450,000 UK adults with white European ancestry who had volunteered to part of the UK Biobank, and their DNA studies for research purposes.

The researchers identified 48,791 people with depression and 291,995 people without depression (controls) whose BMI had been measured, and their DNA.

People were identified as having had a depression based on either:

  • that they had seen a GP or psychiatrist for nerves, anxiety, or depression and experienced at least 2 weeks where they felt depressed or unenthusiastic
  • UK national hospital records showed that they had a diagnosis of recurrent major depressive disorder (MDD) or single-episode MDD

The researchers also looked at whether there were only those people who were diagnosed with depression.

The researchers looked specifically at whether genetic variations were associated with obesity.

As "markers" for obesity, if these genetic variations were more common in people with depression, this would suggest that obesity could be contributing to people's risk of developing depression.

The researchers looked at 73 genetic variations which had been linked to having a higher BMI. The researchers excluded variants that had been linked to having a higher BMI. Of the 73 variants, 43 were in or near to genes, which could have an impact on the brain and nervous system function and development (so they could theoretically affect the depression risk directly) and 30 were not. Also, 14 of the variants were associated with increased BMI and reduced risk of metabolic disease.

If the variants are associated with a higher BMI, but not with any of the metabolic consequences of obesity, they would be found to be more common in people with depression, this might suggest that the link between obesity and depression relates to psychological effects.

The researchers also looked at men and women separately, as it could be because of the psychological impact of obesity. They also have repeated analyzes on a second sample of 45,591 people with depression and 97,647 controls from another study group (the Psychiatric Genetics Consortium).

What were the basic results?

The researchers found that those who were obese had a 45% higher chance of having depression than those in the healthy range (odds ratio (OR) 1.45, 95% confidence interval (CI) 1.41 to 1.49). This link was stronger in women than in men.

Having a combination of genetic variants associated with a higher BMI (about 5kg / m2 higher) was associated with an 18% increase in the odds of having depression (OR 1.18, 95% CI 1.09 to 1.28). The link was slightly stronger in women than men, but the difference was not enough to rule out that much.

The researchers found similar results when they carried out further analyzes to make sure their findings were robust.

The BMI-linked variants were also linked to the brain or nervous system related genes. But again the difference was not enough to rule out that by chance.

The BMI-linked variants were associated with favorable metabolic profile, but only once data was obtained from the Biobank and Psychiatric Genetics Consortium samples were pooled.

How did the researchers interpret the results?

The researchers concluded that a higher BMI is likely to contribute to an increasing individual's chances of developing depression.

Some medications used to treat depression can cause weight gain. People who are depressed may be more likely to take care of themselves, including eating healthily and taking regular exercise, and may also impact their weight.


This study provides evidence that the link between the obesity and the depression may have a direct impact on the person's risk of depression.

This study was very large, and used many complex analyses to look at the relationship between weight, genetics, and depression. The researchers used a study design which was aimed at removing the chance of impacting the results. They also carried out several additional analyzes to test their results and make sure they were reliable.

For example, the way that people have been classified as having a depression may not have been entirely accurate, as it was based on partly on the reports of having a medical professional for "nerves, anxiety or depression". Some people might have had a depression but not a sought help, or a diagnosis of depression had they fully assessed. However, when the researchers excluded people who did not have a hospital recorded depression, they got similar results.

While this study contributes to what is known about the link between obesity and depression, there is still much to be learned. For example, the findings suggest that the link may be a psychological but researcher who will look for more information.

It is also worth bearing in mind that the depression is likely to be complex, with many factors potentially playing a role. Also, the results may not apply to people of different ethnicities.

If you are overweight or obese and you are also troubled by low mood or depression then it may be a good idea to seek help at both the same time.

What we do know is that mental and physical health are interrelated, and regular physical activity and eating are likely to be beneficial for both.

Analysis by Bazian

Edited by NHS Website

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