Alcohol is the leading cause of ill-health in young adults in the UK and Europe and is the fifth leading cause across all ages in the UK population and is estimated to be the seventh leading cause globally . There are over 1 million alcohol related hospital admissions and nearly 25,000 alcohol related deaths a year in England with trends, in stark comparison to other major causes of death, not yet decreasing.

Since our previous grant (ALSPAC Alcohol at 24) there have been several important changes to our understanding of the risks of alcohol, patterns of drinking in the population, and UK response to preventing alcohol related harms.

First, levels of drinking reported by adolescents in UK and many other countries have fallen, corresponding with a fall in alcohol related hospital admissions in those under 18, but not yet resulting in any measurable decline in alcohol related harms in young adults . The motivation, reasons (and potential modifiable factors) causing the decline are not yet known but under investigation. In adults in the UK there is some evidence that changes in alcohol use has been differential with greater reductions in low level drinkers and no change in heavier drinkers with subsequently little overall impact on alcohol related harms. At the same time harmful alcohol use has been recognised as an important contributor to the “deaths of despair” that have reduced life expectancy – especially among poorer and more marginal populations - in North America.

Second, in large well powered genetic studies (and against decades of observational data) the cardio-protective effect of alcohol has been shown to be false – and instead likely to be due to non-causal factors all along (such as confounding, selection bias and reverse causation). This implies that there is no compensation of low levels of alcohol use improving morbidity and mortality and no absolutely “safe” or “non-risky” levels of drinking – and clear benefits from reducing average consumption. The UK in line with other countries issued new guidelines on safe drinking levels – which are now the same for men and women – though evidence is unclear whether there have been any changes in the UK population as a result of the new guidance. Policy changes also are underway – notably in Scotland - based on economic models that show how introducing and raising minimum price of alcohol can reduce future alcohol related morbidity and mortality. [There have been other advances in use of MR and genetic markers to identify new targets for drug discovery, compare the impact of interventions, and test for interactions between behavioural exposures – but in European populations MR of alcohol use and AUD have been limited by lack of robust markers.]

Third, it is argued that alcohol related health harms may be under-estimated in part because cohort studies under-represent heavier drinking marginal populations but also because of an under-appreciation of the interaction of alcohol with other exposures. The burden of alcohol is greater in poorer communities, alcohol combines with other exposures to increase risk of liver disease, and alcohol can act as a “snare” increasing the persistence and halting the resolution of antisocial behaviour. This has led to a renewed focus on understanding how adverse alcohol trajectories develop and interact with other exposures to increase health and social harms to strengthen the evidence base ultimately for policy-makers but also for alcohol policy models that can show the impact of alternative prevention strategies.