Epigenetics examines how expression of our genes are influenced by factors over and above the genetic code. Associate Professor Cohen- Woods’ work at the Flinders Behavioural Genomic and Environmental Mechanisms Lab explores the connection between the forces of genetics, epigenetics and environment on mental health outcomes and fertility, and how early life experiences or even parental experiences can get imprinted and influence behaviour later in life.
“The brain and the body are not separate from each other, so addressing mental and physical heath together is imperative,” says Associate Professor Cohen-Woods. “This is a crux of my work, that behaviour is a union of nature and nurture, not one or the other.”
Reaching across many themes, she is examining genomic risk factors in a range of disorders, conditions and behaviours, from genetic factors affecting basic decision making through to disorders in eating, how autistic behaviours play a part and how much environmental factors may adapt these genetic risks.
This novel line of research is leading to ideas being explored in new ways, demanding very different types of cross-disciplinary collaborations that can bring together hundreds of diverse experts. “New ways of thinking about problems demand the interaction of different skill sets. It’s necessary for this type of science to make a discovery.”
Associate Professor Cohen-Woods learned quickly about the vast scale of studies necessary in this field. In 2009, she thought she was working with a huge cohort, comprising 2,000 people, for one of the first genome-wide studies in depression. “We were convinced we had a solution within reach because we had such a strong cohort but it very quickly became clear to us that, because genetic effects are tiny, our numbers were nowhere near enough. The latest depression study has 800,000 people in the discovery phase and more than one million in the replication. Therefore, large-scale collaborations are vital in this work.”
One significant project she is working on studies intergenerational inheritance and transmission of trauma and stress. “I wasn’t initially convinced it involved molecular transmission, but then a new study using Scandinavian data on men who had lost a parent during their early development period showed an impact on their own children. These children had lower birth weights, more were premature and had differential physical outcomes at birth, so that definitely is not a result of parenting. There’s more that needs to be examined.”
Associate Professor Cohen-Woods acknowledges that epigenetic inheritance is only a theory – any existing evidence in humans is correlational and usually after a period of development – so she is keen to deliver solid research that can tap into mechanisms and early development in humans.
Studies in mice show a severely anxious male’s offspring and subsequent generations display heightened anxiety-related behaviours. Studies have identified changes in the DNA of those male mice’s sperm, even though subsequent generations had never been subjected to the original stress. “This suggests something very interesting, but there isn’t currently similar research in humans – and it’s very difficult to engage men in such research, even more difficult to have them provide sperm for testing,” says Associate Professor Cohen-Woods.
To explore this idea, she has commenced the Flinders Environmental Epigenetics in Life study, being done in collaboration with Flinders Fertility Clinic in Glenelg, South Australia.
After identifying dysregulated genes in the sperm, Associate Professor Cohen- Woods wants to test the blood spots of the babies born to these men. All babies have blood spots taken at birth to do gene testing for specific single-gene disorders, and South Australia stores these samples. “When we get full consent, we will use these to trace – for the first time in humans – a correlation in the germline from parents to children at birth about stress-related trauma.
“This whole line of study started sceptically, but with a keen interest from me – and that’s the best way to run a study. I’m not assuming I’m going to find an effect. I’m going to see if there is an effect and then take that forward.”
Statistics, however, can be confounding – and knowing that correlation is not causation, she is acquiring much more data, on diet, exercise, adult stress, anxiety and depression symptoms. “Going through IVF is stressful; getting through COVID-19 is stressful, so there are many, many factors we have to consider here to identify the confounding elements.”
In identifying future outcomes, Associate Professor Cohen-Woods is cautious. She points to the emergence of companies offering direct-to-consumer genetic testing, and that people can ask to identify specific risk data about the likelihoods of developing genetically translated diseases. “A genetic risk factor is very difficult for most people to understand – and just identifying a risk does not mean it is definitive,” she explains. “We’ve seen that this type of testing did the opposite for people that we thought it would. The people who receive this information are feeling a loss of control over their lives, and they believe there is nothing to stop them from getting the identified problem, whether it be cardio-vascular disease or schizophrenia.”
She believes that if this same type of direct-to-consumer testing happens with epigenetics, it could have a negative impact. “We simply aren’t ready. Firstly, we need to build on epigenetic education – explaining what it is and how it can be used as an environmental motivator to take control of your life. To perhaps switch genes on and off by engaging in various different behaviours,” she says.
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