Surge in new alcohol genes

By
Henrik Larsen
Research Story

Are you a problem drinker? Then, statistically, you’ll also be particularly genetically prone to developing disorders such as depression and insomnia. And to becoming addicted to drugs and tobacco. This is what Danish researchers are helping to prove in a new international study.

Scientists have looked at the role genes play when, year after year, a person drinks such large quantities of alcohol that he or she ends up suffering serious psychological, social and health damage.

The issue of the role of the genes is key, because in most cultural spheres problematic alcohol consumption is one of the main causes of illness, premature death and social problems.

For this reason, science has been trying to identify the so-called risk genes for problematic alcohol consumption for a number of years now – among other things, in the hope of being able to develop new forms of treatment for alcohol addiction.

Until recently, science was only aware of ten gene variants that could be considered risk genes for problematic alcohol consumption. Now, thanks to this new study, which was recently published in Nature Neuroscience, one of the world’s highest-ranking journals in the field of brain research, this number has increased to 29.

The authors of the study are an international team of researchers from the USA, the UK, Germany, Sweden and Denmark.

The Danish members of the team are Associate Professor Mette Nyegaard and Professor Anders Børglum, both from the Department of Biomedicine at Aarhus University and the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH).

Major databases were scoured

If you are trying to understand what risk genes actually are, the first thing to do is work out how to identify them. And, as Associate Professor Mette Nyegaard explains, in order to conduct a search of this kind, you need to have a place to look:

‘You need access to huge quantities of DNA, in the form of complete genetic profiles of several hundred thousand people – in this case, a total of 435,000 individuals.’

The genetic data of these people are stored in three databases – the UK Biobank, the American Million Veteran Program and the international Psychiatric Genetics Consortium – together with all kinds of other information about their health and lifestyle.

With access to these databases, Mette Nyegaard and her colleagues were able to hunt for risk genes for problematic alcohol consumption:

‘The DNA of all 435,000 individuals was systematically analysed. We were looking for incidence of several million different DNA variants – so, special versions of certain genes.’

The intention was to find out whether the participants who were problem drinkers also typically had a higher incidence of certain gene variants than the participants whose alcohol consumption was unproblematic.

The pattern of these risk genes was then compared with the pattern of risk genes for other disorders. The researchers were able to see:

*That problematic alcohol consumption is genetically closely related to a range of psychiatric disorders.

*That problematic alcohol consumption is also genetically closely related to drug abuse and smoking.

These coincidences became clear once the researchers had completed their calculations. However, it is important to understand what this actually means – and, in particular, what it doesn’t mean. Mette Nyegaard explains:

‘Basically, we’re now beginning to glimpse the contour of a genetic architecture. A kind of relationship between alcohol abuse and abuse of other substances – and between alcohol abuse and psychiatric disorders such as ADHD and depression. So, there’s a genetic component that plays a part here. But the study also shows that the genes are not the whole story, and they’re not the only thing that determines the overall outcome. Other factors such as environment will very much come into play,’ says Mette Nyegaard.

The risk genes identified by the research team provide new insights into the biological mechanisms involved when someone becomes a problem drinker.

The hope is that, in time, this knowledge will help us design new drugs that will significantly suppress – and ideally eliminate – alcohol addiction in human beings.

It is not yet known whether there are drug candidates of this calibre among the 29 risk genes for problematic alcohol consumption which have now been identified. However, the study in Nature Neuroscience demonstrates that 16 of these genes are actually so-called drug targets. This means that they may be affected by known pharmaceutical substances.

The study also shows that the gene variants which, to some degree or other, promote problematic alcohol consumption also contribute to insomnia.

 

Definitions

The term ‘problematic alcohol consumption’ used by the researchers in the article in Nature Neuroscience refers to:
*People who have been specifically diagnosed with alcohol addiction.
*People with no diagnosis but who have themselves reported that their personal alcohol consumption led to social, psychological and health problems.