New study uses DNA methylation quantitative trait loci to characterize the relationship between methylomic variation, gene expression and complex traits

A new paper from our group published in the American Journal of Human Genetics highlights the utility of DNA methylation quantitative trait loci (mQTLs), for interpreting the functional consequences of common genetic variation associated with human traits. We describe the first comprehensive analysis of common genetic variation on DNA methylation using the Illumina EPIC array to profile samples from the UK Household Longitudinal (Understanding Society) study. We identified >12 million significant DNA mQTL associations including a large number not identified using previous methylation-profiling methods (i.e. the Illumina 450K array). We demonstrate the utility of these data for interpreting the functional consequences of common genetic variation associated with > 60 human traits, using Summary data–based Mendelian Randomization (SMR) to identify pleiotropic associations between complex traits and DNA methylation sites. We also use SMR to characterize the relationship between DNA methylation and gene expression. Our mQTL database and SMR results are available via a searchable online database as a resource to the research community.

Major funding to explore genomic changes in dementia

The research seeks to examine the way in which gene function changes at different stages of dementia

Exeter researchers will join forces with global experts to investigate the mechanisms behind Alzheimer’s disease, in a project announced on World Alzheimer’s Day (September 21).

The Exeter team, led by Professor Jonathan Mill, has been awarded almost £450,000 by Alzheimer’s Research UK (ARUK) to research the genomic mechanisms involved in progression of the disease. The University will team up with Eli Lilly and Company Ltd, who will collaborate with Exeter on the project as well as providing considerable matched funding.

Worldwide, nearly 44 million people live with Alzheimer’s disease or a related dementia. Alzheimer’s disease is associated with the build-up of proteins called tau and amyloid which form clumps that are damaging to brain cells. The driving mechanisms behind these changes in the brain involve both genetic and environmental factors, which are only partly understood. Further research is needed to fill the gaps in our knowledge and develop better treatments.

The project, starting in October, will use mouse models that reflect aspects of human Alzheimer’s disease to examine the way in which gene function changes at different stages of the disease. Researchers will measure the expression and regulation of genes in different regions of the brain, aiming to relate changes in gene function to changes in the progression of the disease.

Professor Mill said: “We’re delighted Alzheimer’s Research UK has funded our project, which aims to test the hypothesis that the development of Alzheimer’s disease pathology is associated with changes in the activity of genes in affected brain regions. The project brings together experts in genomics, informatics and neuroscience, and represents a novel approach for identifying the mechanisms involved in the progression of this terrible disease.”

Dr Rosa Sancho, Head of Research, at Alzheimer’s Research UK, said: “Currently 87,000 people in the South West are living with dementia, a condition which can rob people of their most precious memories and turn lives upside-down. Alzheimer’s disease is the most common cause of the condition, and while age is a big risk factor for the disease, it is not a normal part of ageing. Understanding the complex genetic processes contributing to Alzheimer’s disease is crucial in the hunt for new breakthroughs which will save lives.

“Exeter University is world-leading in this area of research, and we are very pleased to be funding Prof Mill’s pioneering project. Alzheimer’s Research UK receives no government funding for the research we support, and it is only thanks to the generosity of our supporters that we’re able to fund vital projects like this.”

The team will investigate how the findings identified in mouse brain compare to human genes by testing specific changes in their Alzheimer’s disease datasets.

Ultimately, we expect that the project will improve our knowledge of the underlying biological mechanisms leading to Alzheimer’s disease, which will allow is to nominate potential drug targets and biomarkers for treatments of the disease.

To find out more about dementia research at Exeter, follow #ExeterDementia on Twitter or visit our dementia website:

Date: 21 September 2018


Emma Walker

Emma is a PhD candidate and bioinformatics graduate research assistant with the Complex Disease Epigenetics Group at the University of Exeter Medical School. She graduated with a BSc in Biological Sciences from the University of Exeter after studying an Access to Higher Education Diploma in Brighton. During her degree she discovered a passion for bioinformatics and statistical modelling, and a fascination for how these can be combined with genomic data to tackle cutting edge questions in science. Her current work focuses on the regulatory genomic signatures of human brain development within the context of neuropsychiatric disorders.


Helena Jones

Helena Jones is a third year BSc Medical Sciences (Genomics) student at the University of Exeter. She is now currently on her Professional Training Year, where she will be assisting with Dr. Emma Dempster’s research. Her project is titled “Epigenomic pathways linking obesity, mood and clinical depression”.