Alcoholism: is it in your genes?
You may have wondered how your grey cells are affected by how much you drink. You may have wondered if some people are born to be alcoholics, or whether it is just an unfortunate series of life experiences and personal decisions. Scientists are undertaking hundreds of studies into the relationship between alcohol and our brain structure – a few examples of which will be reviewed here.
Generally speaking, the study of the neuroscience of alcohol tends to look at the pathology of drinking – in other words, excessive drinking of alcohol. This is broadly understood as regularly drinking more than 14 units every week.[1] To test how alcohol affects the brain, many studies use a sliding scale of how much alcohol people drink a week to observe what different effects are seen. People of course tend to underreport how much they’ve drunk – the famous influence of social desirability – so this is always something to bear in mind with this area of research.
This review will be split into three parts, each looking more closely at the genetics and brain differences involved in our behaviour around alcohol. Most studies look at the brains of people with alcoholism, but research is now starting to look at how the brains of moderate drinkers may also be affected by alcohol. This is Part II: ‘Alcoholism: is it in your genes?’
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New research about the relationship between alcohol and the brain is heading down the road of genetics. This often involves comparing reels of genetic sequencing with the pattern of alcohol use over a person’s life. This kind of research questions whether those who become alcoholics born to do so because of their genes… or whether it may be more a result of adverse life experiences and personal decisions.
In 2020, one study set out to investigate this particular uncertainty[2]. Using the data from 435,563 individuals, an analysis was conducted to compare each person’s genetic information with their history of alcoholism. More specifically, they ran the rather wordy ‘proxy-phenotype meta-analysis’ on the data, which led to the discovery of 29 significant phenotypes (observable genetic traits) which lead to problematic alcohol use. Nineteen of these were previously undiscovered. This vital biological insight into the genetic patterning of alcoholism is supported by previous and equally large meta-analyses[3], suggesting that alcoholism is in a large part down to your genes.
This understanding however mustn’t tip over into assuming that people are born with the exact genes leading to alcoholism, and that their path is pre-determined. Aside from leaning into an unneeded fatalism, biological processes are rarely that simple and a number of other things are involved. For example, this study also found a further 138 other traits which correlated with problematic alcohol use. The strongest associations were found with other substance use and substance disorders, and several other psychiatric conditions including schizophrenia and major depressive disorder. Alongside this, several factors like higher risk-taking behaviour and number of sexual partners increased people’s likelihood of falling into alcoholism, whilst their cognitive performance and educational achievements were found to act as a protective factor against this. These findings bring in the important strand of ethical responsibility – if certain factors like education can protect people from later alcoholism, then the need to engage and support all children in school is ever more underlined. Thus, numerous other factors interplay with significant genetic patterning to lead someone into alcoholism.
When considering how research like this can be helpful – aside from simply understanding alcoholism more – it becomes particularly useful when you consider the treatment of problematic alcohol use. The genetic correlations this study found showed enrichments in very specific regions of the brain – meaning that they could pinpoint accurately the brain tissues involved in these genes’ expression. By combining these findings with the actions of various drugs, researchers identified two regions of particular interest for targeting with precision medicines. The first is the D2 dopamine receptor, which is found most commonly in the basal ganglia in the centre of the brain. Already targeted by a lot of antipsychotic medications, the D2 dopamine receptor is very important in the processes of regulating dopamine release in the brain.[4] And the other is phosphodiesterase 4B – an enzyme which is involved in cell signalling in the brain.[5] Because of the higher frequency of risk variation genes found at these points, novel treatments of alcoholism would do well to target them.
Overall, this is a fascinating and novel study into the genetics underlying the problematic use of alcohol. With many notable avenues for research, it is an exciting addition to the literature on the relationship between alcohol and the brain. However – like the study considered in Part I –the databank itself primarily contains the data of white European people. Despite using a huge sample size and having a wider age range than the first study, there is still an urgent need to widen who is tested, so that results can be more confidently generalisable across the world. As well as this, whilst the study had good statistical power – enough to detect these genes and other factors associated with alcoholism – the power was not enough to test the validity of each individual variant discovered. In other words, we cannot confidently say that each of those 29 phenotypes was responsible for people’s alcohol use. This means that more studies should be done on these specific variants to increase the strength of our understanding. All in all, this study is an exciting leap as we learn ever more about the relationship between our genetics, our brain, and how we drink.
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Follow through to Part I: ‘An Aperol a Day’ and Part III: ‘The Age of the Frontal Lobe’!
References
[1] NHS (n.d.) Alcohol Misuse. NHS. Available at: https://www.nhs.uk/conditions/alcohol-misuse/
[2] Zhou, H., Sealock, J.M., Sanchez-Roige, S. et al. (2020) Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits. Nat Neurosci 23, 809–818.
[3] Kranzler, H. R. et al. (2019) Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations. Nat. Commun. 10, 1499.
[4] Ramanathan, S., Irani, S.R. (2018) Reference Module in Neuroscience and Biobehavioural Psychology. Science Direct. Available at: https://www.sciencedirect.com/topics/neuroscience/dopamine-receptor-d2
[5] Tibbo AJ, Baillie GS. (2020) Phosphodiesterase 4B: Master Regulator of Brain Signaling. Cells. 9,5. 1254.