Scientists have shed light on the complicated relationship between the makeup of our DNA and how much alcohol we drink.
In another study, they have explored the links between our genes and our intake of salt.
Genetic markers linked with alcohol intake
In the first study, published in Nature Human Behaviour, the international team, led by Imperial College London, identified new genetic markers associated with alcohol intake.
After analyzing data from around 500,000 people – most aged between 40-69 – the team identified 46 new genetic markers linked to how much alcohol people drink.
The researchers found these genetic factors could account for seven percent of the variation in people’s total alcohol intake.
Those with the lowest alcohol-related genetic risk drank about one third less of a standard drink per day (2.6g of alcohol) compared with those with the highest.
The team also identified genetic pathways shared between alcohol intake and brain networks, in particular networks associated with psychiatric disorders such as schizophrenia.
This could suggest that a person’s alcohol intake and their risk of schizophrenia may be influenced by some of the same genes.
Professor Paul Elliott, lead author of the study from Imperial’s School of Public Health, said: “This study suggests the amount we drink is not just socially determined, but also has a biological basis.”
He continued: “Although we already knew there was an association between schizophrenia and alcohol drinking, this research suggests there may be some joint genetic mechanism that leads a person to drink more, as well as increase their risk of schizophrenia.”
The paper also revealed one particular genetic variant was linked to size of a brain region called the putamen, which was in turn linked to alcohol intake.
Professor Elliott added that the research was based on data from people with European ancestry, and so data from other ethnicities should also be investigated. But the research furthers our understanding of our complicated relationship with alcohol:
“Excessive alcohol consumption is a major public health problem, and associated with around one in 20 deaths worldwide. If we understood more about the biology of why we drink alcohol, we may be able to understand more on how to effectively deal with alcohol issues.”
Genes associated with salt intake
In another study published today in the journal Nature Communications, the same team investigated the genes linked to people’s intake of sodium, the main component of salt, and potassium.
The research team investigated data from nearly 500,000 people, and assessed genes associated with sodium and potassium urinary excretion, which are measures of the amount of sodium and potassium in the diet.
Both sodium and potassium are crucial to many processes in the body, but excess sodium is linked to an increased risk of heart attack and stroke.
The team found 59 genetic markers linked to either sodium or potassium intake or both. The team found that many of these variants were also linked to lifestyle-related variables such as dietary habits, smoking, coffee and alcohol drinking..
The research also reported that genetic variants linked to sodium were linked to gene variants associated with obesity, lipid levels, high blood pressure and cardiovascular disease, and raised the possibility that sodium genetic variants are involved in temperature pathways in the regulation of blood pressure.
Professor Abbas Dehghan, lead author of the research from the School of Public Health, said: “Our study is the first to identify genetic variants linked to sodium and potassium in urine, which reflect dietary intakes.
Our work gives us more insights into the link between sodium intake, high blood pressure and cardiovascular disease and reinforces public health messages of reducing salt intake to reduce cardiovascular risk.”.
Alcohol use disorder (AUD) is a devastating public health problem that causes a large economic burden.
The lifetime prevalence is estimated to be 17.8% for alcohol abuse and 12.5% for alcohol dependence (1), reflecting the necessity of developing effective prevention or treatment strategies.
From the neurobiology perspective, the progression from controlled alcohol use to compulsive and addictive behaviors is hypothesized to be encouraged by reinforcement and neuroadaptation mechanisms, where alcohol exposure elicits neuroadaptive changes which promote drug-related responses (i.e., reinforcement) (2, 3).
It has been revealed that the process of developing AUD is largely shaped by genetic and environmental factors that affect the vulnerability to initial use and to shift from use to addiction (4, 5).
Family and twin studies estimate the heritability to be 0.5–0.7 for alcohol dependence (6–8) which has been well-acknowledged as a complex polygenic disorder (5, 9).
The remaining variability in liability is likely attributable to individual specific environmental factors rather than those shared by families (7).
Hence, it is not surprising that there has been growing interest in exploring epigenetic mechanisms in AUD.
Epigenetics integrates genetic and environmental effects (e.g., emotional stressors and social adversities) and can influence biological functions through regulating gene expression (10).
Growing evidence supports that epigenetic regulation is one major mechanism through which alcohol consumption and stress result in changes in synaptic systems and neurocircuitry, which contribute to further changes in drinking behavior (11, 12).
One commonly studied epigenetic mechanism is DNA methylation (DNAm), which is predominantly found in cytosines of dinucleotide sequence of CpG (10).
With respect to AUD, it has been shown in animal studies that alcohol exposure appears to induce transgenerational alterations in DNAm patterns that influence gene expression and neuronal functions in hypothalamus involved in neuroadaptation (13).
In humans, altered promotor DNAm levels in peripheral blood have been reported in a variety of genes related to AUD, including dopamine transporter (DAT) (14), N-methyl-D-aspartate 2b receptor subtype (GRIN2B) (15), nerve growth factor (NGF) (16), and μ-opioid receptor (OPRM1) (17), suggesting the potential of these DNAm sites in peripheral tissue as biomarkers for AUD. A hypothesis-free epigenome-wide DNAm analysis has provided evidence for calcium signaling and immune system process also being involved in the pathology of alcohol dependence (18).
No definitive causal relationship can yet be inferred from the observed associations, nevertheless it is speculated that epigenetics may play both roles of predisposition and response in the model of drug abuse (19).
While epigenetics poses a valuable means to elucidate the interactive effects between genetics and environmental factors on AUD, one particularly interesting angle is its dynamic nature, which may shed light on intervention and treatment.
DNAm is shown to be a reversible biological signal through pharmaceutical or behavioral interventions, where DNAm patterns in part determined by maternal behavior could be reversed with cross-fostering or methyl supplementation and could further impact on phenotypic outcome (20–22).
Extensive efforts have been devoted to programming DNAm through pharmaceutical actions (23).
In addition, there has been converging evidence that, physical exercise, as a well-known non-invasive beneficial stimulus, boosts physical and mental health, including cardiac fitness, immune system, as well as, neuronal and cognitive conditions (24–26). Recently it has been shown that exercise modifies the epigenome-wide DNAm pattern that may be inherited to future generations (27, 28).
Notably, one study demonstrates that exercise impacts DNAm and mRNA levels of BDNFin the rat hippocampus, suggesting exercise playing some role in transcriptional regulation of synaptic plasticity (29) which is the primary mechanism underlying neuroadaptation (2).
Direct evidence of exercise moderating the effect of heavy alcohol consumption on white matter damage has also been documented (30).
Thus, it is an intriguing question whether exercise can be a treatment strategy in a way of reversing epigenetic changes that contribute to development of addiction. While a longitudinal design to compare methylation in drinkers before and after exercise intervention is needed to comprehensively explore this issue, the current study aims to exploit available resources to provide preliminary results for assessing if this topic deserves further attention.
We conducted blind epigenome-wide association analyses on three datasets: a longitudinal exercise intervention cohort comparing baseline vs. post-exercise intervention follow-up; a cross-sectional cohort of age- and sex-matched hazardous drinkers vs. controls; and a cross-sectional cohort of binge drinkers only.
We first identified methylation sites significantly associated with pre- vs. post-exercise in the exercise intervention cohort. In parallel, we identified methylation sites that not only exhibited significant differences between hazardous drinkers and controls (case-control cohort) but also showed linear associations with drinking behavior (drinking cohort).
Then among the markers associated with both exercise and drinking, we focused on those markers showing opposite directions of associations between exercise and drinking, and further explored their multivariate associations with drinking behavior.
More information: Evangelos Evangelou et al. New alcohol-related genes suggest shared genetic mechanisms with neuropsychiatric disorders, Nature Human Behaviour (2019). DOI: 10.1038/s41562-019-0653-z
Journal information: Nature Communications , Nature Human Behaviour
Provided by Imperial College London
