Using genetics to identify dementia risk factors

Scientific Title: Using genetic data to identify early life determinants and causal environmental risk factors for Alzheimer’s disease

What do we already know?

Most of the evidence on the role of non-genetic risk factors for Alzheimer’s disease (AD) has been from observational studies in adults. These studies have suggested that cardiovascular, anthropometric and cognitive factors may be involved in the development of late-life AD, but the findings are conflicting. Confounding factors, such as cardiovascular disease or socioeconomic factors, may result in biased estimates of associations between risk factors and AD. In addition to potential confounders, bias due to reverse causation may also occur in epidemiological studies of AD risk factors, making it difficult to establish the direction of effects (for example whether the hypothesised risk factor causes AD, or is a consequence of the disease). Consequently, there is currently no consistent evidence for environmental risk factors which can be modified to decrease the risk of AD. Genetic variants, identified from large genetic studies, are a useful tool for researching the aetiology of AD if they are used as proxies for potential risk factors. This is because genetic variants are randomly assigned at conception for each individual and they cannot be influences by the disease or confounding factors. 

What is this project trying to find out?

We will investigate 1) whether there is a shared genetic component between AD and early life lipid levels, glycaemic, anthropometric, behavioral and cognitive traits, and 2) whether any of these environmental risk factors are causally related to AD.

How will they do this?

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a large cohort study of mothers and their children, for whom longitudinal information on behavioural, cognitive and psychiatric outcomes has been collected at multiple time points. Blood samples have also been collected to measure levels of blood markers such as lipids and glycaemic traits. Genetic data are available on more than 9,000 mothers and their children.  Using these genetic data we will calculate genetic predictors for each individual in the ALSPAC study (mothers and their children) and investigate the genetic overlap between AD and plasma lipid levels, anthropometric and cognitive traits for both children and their mothers. To infer causality for environmental risk factors of AD, we will use Mendelian randomisation; genetic variants will be used as proxies for modifiable exposures and the causal association between these and AD will be estimated. 

Why is it important?

Understanding early life risk factors will provide insight into potentially effective screening and preventative methods. As no cure exists for Alzheimer’s disease and pathological changes can occur more than two decades before the onset of symptoms, the identification of early life modifiable risk factors is of immense public health importance.

Further information

Please click here for more information on the work of Dr Evie Stergiakouli.

Please click here for more information on the work of Dr Emma Anderson.

Please click here for more information on the work of Dr Laura Howe.

Please click here for more information on the work of Prof George Davey Smith.