Excessive alcohol consumption and genetic risk as determinants of alcohol-related liver disease Summary Alcohol-related liver disease ( ARLD) represents a significant public health burden. The identification of high-risk people would allow public health interventions to be efficiently targeted. Here, we show significant interactions between alcohol consumption pattern, genetic predisposition (polygenic risk score, PRS) and diabetes mellitus, and risk of incident ARLD, in 312,599 actively drinking adults in the UK Biobank. Excessive alcohol consumption and binge drinking significantly increase the risk of alcohol-related cirrhosis (ARC), and a greater genetic predisposition further amplifies the risk. Furthermore, we demonstrate a pronounced interaction between heavy alcohol consumption and a high polygenic risk score (PRS), resulting in a relative excess risk due to interaction (RERI) of 6.07. Diabetes consistently elevated the risk of ARC across all categories of alcohol consumption and PRS, and showed a significant interaction with both binge eating patterns and genetic risk. Overall, we demonstrate synergistic effects of heavy alcohol consumption, genetics, and diabetes on ARC, with potential to identify high-risk individuals for targeted interventions. |
Comments
Those who drink excessively and have a certain genetic makeup are six times more likely to develop alcohol-related cirrhosis, according to new research from UCL, the Royal Free Hospital, the University of Oxford and the University of Cambridge.
The study, published in Nature Communications , is the first to evaluate how an individual’s behavioral pattern of alcohol consumption, their genetic profile (via a polygenic risk score), and whether or not they have type 2 diabetes affect their risk of developing alcohol-related cirrhosis (ARC).
The observation that alcohol consumption pattern is more important than volume , along with the increased risk when genetic makeup and type 2 diabetes are also present, provides more precise information to identify those most vulnerable to liver disease.
Liver disease is one of the leading causes of premature death worldwide: between 2% and 3% of the world’s population suffer from cirrhosis (scarring of the liver) or liver disease. Since the COVID-19 pandemic began, alcohol-related deaths have increased by 20%.
In this study, researchers analyzed data from 312,599 actively drinking adults in the UK Biobank cohort, to assess the impact of alcohol consumption pattern, genetic predisposition and type 2 diabetes on the likelihood of developing cirrhosis related to diabetes. alcohol (ARC).
A baseline hazard ratio (HR) of one was established using data from participants who reported drinking within daily limits, had a low genetic predisposition to ARC, and did not have diabetes.
Those who drank excessively, which is classified as consuming 12 units a day at some point during the week, were three times more likely to develop alcohol-related cirrhosis (ARC). The risk for those with a high genetic predisposition was four times higher and the risk for type 2 diabetics was two times higher.
Dr Linda Ng Fat, first author of the study from UCL Epidemiology & Public Health, said: “Many studies looking at the relationship between liver disease and alcohol focus on the volume of alcohol consumed. We took a different approach by focusing on the pattern of alcohol consumption and found that this was a better predictor of liver disease risk than volume alone. The other key finding was that the more risk factors involved, the greater the “excess risk” would be due to the interaction of these factors.”
When heavy alcohol consumption and a high genetic predisposition were at play, the risk of developing ARC was six times higher than the baseline risk. The addition of type 2 diabetes also resulted in an even higher risk.
Dr Gautam Mehta, lead author of the study from the Division of Medicine at UCL and the Royal Free Hospital, said: "Only one in three people who drink at high levels develop serious liver disease. While genetics plays a role, This research highlights that the pattern of alcohol consumption is also a key factor. Our results suggest, for example, that it would be more harmful to drink 21 units in a couple of sessions than to spread them evenly over a week. Adding genetic information, which can be widely used in healthcare in the coming years, allows for even more accurate risk prediction.”
Although polygenic risk scores are not in widespread clinical use at this time, they are likely to be more commonly used as a method to define personalized disease risk.
Dr Steven Bell, lead author of the study from the University of Cambridge, said: "As liver diseases, particularly alcohol-related deaths, have seen a significant increase since the start of the COVID-19 pandemic , It is imperative that we adopt innovative strategic measures to address this growing crisis. This study provides us with novel tools that are essential to identify those most at risk, allowing us to more effectively target interventions towards those who will benefit the most. ”.
Pamela Healy, chief executive of the British Liver Trust, said: “This research is important because it reveals that what matters is not just how much you drink overall, but also how you drink. Drinking too much, too fast, or drinking until you get drunk can have serious consequences for your liver health. Over the last twenty years, as alcohol has become more accessible and affordable, there has been a disconcerting change in the drinking culture in the UK. “The UK needs to tackle rising alcohol consumption through a joint ‘alcohol strategy’ that includes taxation, tighter controls on alcohol advertising and marketing and greater awareness of the dangers of excessive alcohol consumption.” .
Final message In conclusion , these data demonstrate strong associations between heavy alcohol consumption, genetic susceptibility and diabetes mellitus with the risk of developing alcohol-related cirrhosis (ARC) in a UK population cohort, and novel and synergistic interactions between these risk factors. Furthermore, interactions between heavy alcohol consumption and diabetes mellitus were validated in an external Chinese cohort. These findings support stratification of drinkers for cirrhosis screening, behavioral intervention, or selection for clinical trials, based on a combination of these risk factors. Further validation and prospective testing of the clinical risk score based on alcohol consumption pattern and/or genetic risk is warranted, given the heavy and increasing burden of alcohol-related liver disease (ARLD) worldwide. |
