Now, UNC School of Medicine scientists and colleagues are figuring out which of these variants have a causal effect in the development of the schizophrenia. They are finding that some of genetic variants regulate or alter the expression of genes involved in the condition.

Published in the journal Cell Genomics, this research marks a big step forward in our understanding of the genetic basis of schizophrenia.

“Our findings not only provide insights into the intricate regulatory landscape of genes, but also propose a groundbreaking approach to decoding the cumulative effect of genetic variants on gene regulation in individuals with schizophrenia,” said senior author Hyejung Won, Ph.D., associate professor of genetics at the UNC School of Medicine. “This comprehension could potentially pave a path for more precise interventions and therapies in the future. Right now, therapeutic options are limited, and some people do not respond to drugs available.”

For this study, Won and first authors Jessica McAfee and Sool Lee, both UNC-Chapel Hill graduate students, led a team of researchers from UCLA, Harvard, the University of Michigan, and Human Technopole in Italy to explore the genetic variants already linked to the risk of schizophrenia through GWAS research. Their goal was to figure out a way to tease apart meaningless variants from those with potential for biological activity important for developing schizophrenia. This isn’t easy for a few reasons, one of which is that genetic variants are often inherited together from parents. So, right next to each other could be two genetic variants associated with the condition — one might be important for gene expression that plays a major role in the condition, but the other variant might not have any role in the condition.

To tackle this problem, the researchers used a special technique called a massively parallel reporter assay (MPRA) — essentially a genetic sequencing technique that can parse which variants trigger gene expression and which ones don’t. To use this method, the researchers introduced the 5,000 variants into human brain cells in a dish, cells that are essential for early brain development. These variants may or may not cause the expression of their downstream gene and genetic barcode. The barcode, a 20bp DNA sequence, is unique to each variant. This is what the group uses to distinguish the variant sequences. The MPRA revealed 439 genetic variations with actual biological effects, meaning they can alter expression of gene.

“Traditionally, scientists have used other epigenetic data, such as transcription factor binding and biochemically defined enhancers, to identify variants with biological effects,” Won said. “However, these conventional methods failed to predict a large portion of variants we identified to have biological effects. Our work points to a wealth of unexplored variants with biological effects.”

To understand how these variants work together to influence gene activity, Won and colleagues developed a new model that combines data from MPRA with chromatin architecture of brain cells — that is, the genetic information important for how brain cell DNA is organized. By doing this, the researchers could connect these 439 variants to how genes are turned on or off.

“Schizophrenia is a complex condition that is highly heritable,” Won said. “To find these 439 potentially causal variants is a big step, but we still have a lot of work ahead to figure out the complicated genetic architecture that leads an individual to develop this condition. With that information in hand, we could begin to understand the biological mechanism underlying this complex disorder, which may eventually lead to targeted therapies.”

The authors of new research led by the University of Exeter have warned that women who discover, outside of a clinical setting, that they carry a disease-causing variant in one of the BRCA genes (BRCA1 or BRCA2) may be told their risk of breast cancer is 60-80 per cent. In fact, the risk could be less than 20 per cent if they do not have a close relative with the condition.

The warning has emerged in a paper published today in the Lancet journal eClinical Medicine. Until recently, women who received BRCA results did so because they attended clinic due to symptoms, or a family history of disease. The likelihood of certain BRCA variants causing breast cancer has been calculated based on this already high-risk group. However, many people now pay for home DNA testing kits, or are given results as part of taking part in genetic research, without ever having any personal link with breast cancer. The new research, funded by the Medical Research Council, was conducted to get a better idea of the true risk level of these BRCA variants in the general population.

The authors analysed more than 454,000 participants recruited between the ages of 40 and 69 in the UK Biobank study, which collects DNA samples and asks participants to report illness in themselves as well as parents and siblings. They found that simply carrying a disease-causing BRCA variant was linked to a breast cancer risk of 18 per cent (for BRCA2) and 23 per cent (for BRCA1) by age 60. Having a close relative who has had the condition elevated the risk to 24 per cent (for BRCA2) and 45 per cent (for BRCA1) .

Lead author Dr Leigh Jackson, of the University of Exeter Medical School, said more women were choosing to have breast cancer surgery, particularly since actress Angelina Jolie shared her family history of the disease and subsequent genetic test and surgery. But he said: “Being told you are at high genetic risk of disease can really influence levels of fear of a particular condition and the resulting action you may take. Up to 80 per cent risk of developing breast cancer is very different from 20 per cent. That difference could well influence the decision you make around whether you have invasive breast surgery. Some women may decide to go ahead with that procedure knowing that the risk is 20 per cent, but we want them to make an informed decision. We’d urge that anyone communicating cancer risk does so based on a detailed family history, not just genetics alone.”

The research team found a similar result when looking at genetic risk of Lynch syndrome, a genetic condition which increases the risk of colon cancer and some other cancers. The authors also concluded that genetic screening for these conditions in the general population could result in large numbers of people being exposed to needless scans or further procedures.

Co-author Professor Caroline Wright, of the University of Exeter Medical School, said: “Our findings will not just apply to breast and colorectal cancer. All risk estimates of genetic disease have so far largely been based on relatively high-risk groups who attend specialist clinics, so they will not necessarily translate to the general population. This finding has important ramifications for population screening using genome sequencing. We need to ensure we are carrying out research to find the true risk level, and also to be responsible in how we communicate risk, to avoid unnecessary fear and distress which may lead to avoidable procedures.”

If you’re given a high genetic risk of any disease outside of a clinical setting, we’d advise you to speak to your doctor, who will be able to take into account a range of factors including family history to assess whether the risk may be worth investigating further.

Professor Joerg Henning and his colleagues at The University of Queensland School of Veterinary Science have analysed data from the UQ-developed KoalaBASE.

“Car strikes, dog attacks and chlamydia-induced illnesses are injuring and killing an incredible number of koalas across the South East Queensland,” Professor Henning said.

“In the five years between 2009 and 2014, 52 per cent of reported wild koala deaths were caused by car strike, 34 per cent were from a chlamydia-related disease and 14 per cent were because of a dog attack.

“This equates to 1,431 koala deaths from a car strike, 943 chlamydia-related deaths, and 395 dog attack deaths in just five years.

“Remember that these deaths were just the reported cases, so the real numbers would be significantly higher.”

KoalaBASE has been collecting data since 1997 across 15 local government areas from the Fraser Coast, to the Scenic Rim and Darling Downs and the South Burnett.

Dr Ravi Dissanayake conducted the initial analysis, supervised by UQ colleagues and Professor Mark Stevenson at the University of Melbourne.

Data considered in the analysis included dog registration numbers, the human population and dwelling information, as well as road type and road length.

“This analysis is a useful starting point for more pro-active approaches to managing preventable wild koala mortality risk,” Professor Stevenson said.

“There are plenty of policies that could reduce car and dog impacts on South East Queensland’s dwindling wild koala populations.”

Professor Henning suggests that more road signs could alert motorists to reduce their speed in known koala habitat and activity areas.

“Construction of over and underpasses is also essential to ensure the safe movement of koalas through their habitat,” Professor Henning said.

“And information campaigns could help reduce the numbers of dog attacks on koalas by reminding owners to leash their dogs or keep them fenced in areas — it’s vitally important to reduce koala deaths caused by dogs.

“Our research included plenty of mapping, so we’re now keen to work with policymakers to identify specific areas where intervention efforts can help to reduce koala deaths.”