Genetics & Epigenomics

The overall aim of this group is to identify the genetic and epigenetic factors associated with brain ageing and age-related decline and disease. To this end, we investigate these questions using data from the Sydney Memory and Ageing Study, the Older Australian Twins Study and the Sydney Centenarian Study. We have collected genotyping, epigenetic and gene expression data for many of our study participants. Our group has many collaborations with national and international research groups and consortia, as often large sample sizes are required to identify genetic/epigenetic factors that contribute to complex traits and disease. The findings of this work have facilitated the identification of novel genes and pathways that contribute to a wide range of traits, including brain structure and cognitive performance, leading to new insights into the underlying biology. Ultimately, we aim to translate these findings into diagnostic, preventative and/or treatment strategies to promote healthy ageing.

Group Leader: Dr Karen Mather Staff: Dr Anbupalam Thalamuthu, Dr Sumangali Gobhidharan, Dr Naga Mutyala, Sri Chandana Kanchibhotla Students: Mary Revelas, Adith Mohan, Jessica Lazarus, Irina Freitag, Toyin Abdulsalam, Annabel Matison, Russell Chander

In 2020 Dr Karen Mather was awarded a $100,000 Rebecca Cooper Grant to research the molecular processes underlying brain ageing. The grant, entitled ‘Unravelling human brain ageing – a multi-omics approach', will be used to investigate epigenomic age-related changes in brains from deceased adults aged up to 103 years of age.

A world-first international genetics study co-led by Dr Karen Mather has identified genetic variants for two neuroimaging abnormalities – periventricular and deep white matter hyperintensities. The findings were published in Stroke.

White matter hyperintensities are an age-related brain abnormality, commonly observed on neuroimaging scans of older adults, and begin to appear in approximately 50% of all adults in their mid-late 40s and progress with age.

A high burden of white matter hyperintensities has been associated with negative health outcomes, such as stroke. They are thought to be related to brain small vessel disease but the causal factors are still largely unknown.

Traditionally, total white matter hyperintensity volume has been examined but it is also possible to distinguish between deep and periventricular white matter hyperintensities based on their location in the brain. These two categories are thought to reflect different pathological, physiological and functional differences. Genetics plays a significant role in the development of deep and periventricular white matter hyperintensities as shown in our own twin study, OATS, and by other family studies. In the first genome-wide association studies of these two categories, Dr Mather used data from over 26,000 participants from CHeBA’s Sydney Memory and Ageing Study and the Older Australian Twins Study, as well as international studies from the CHARGE and ENIGMA consortia and the UK Biobank. The research assessed participants aged 45 years and older who were free of stroke and dementia. Genetic variants that were associated with both periventricular and deep white matter hyperintensities on chromosome 17 were found.

Importantly, a number of other genetic variants were identified for periventricular white matter hyperintensities only, suggesting that these two neuroimaging measures have shared but also different genetic underpinnings.

Dr Mather said that a large genetics study such as this one provides further evidence that these subclassifications of white matter hyperintensity are two separate entities that may have different implications for brain health – and are therefore important neuroimaging measures to study.

Congratulations to

who in July 2020 was promoted to Senior Research Fellow.