Genomics in the News

Intracerebral hemorrhage (ICH) survivors are at high risk for recurrent stroke and cardiovascular events. Blood pressure (BP) control represents the most potent intervention to lower these risks, but optimal treatment targets in this patient population remain unknown. In this manuscript by CGM Investigators Jonathan Rosand, Christopher Anderson, Alessandro Biffi and colleagues, more intensive BP control than current guideline recommendations had a significantly greater effect on reducing the risk of major adverse cardiovascular and cerebrovascular events and mortality in the months to years following the initial stroke. This work has important implications for the way blood pressure is managed following this devastating form of stroke, and warrants study in a dedicated, randomized controlled trial.

Detecting obstructive sleep apnea (OSA) is important to both prevent significant comorbidities in people with Down syndrome (DS) and untangle contributions to other behavioral and mental health diagnoses. However, laboratory-based polysomnograms are often poorly tolerated, unavailable, or not covered by health insurance for this population. This work published by CGM investigator Brian Skotko and colleagues leveraged a previously developed prediction model that held promise in identifying which people with DS might not have significant apnea. In a novel set of participants with DS, a clinically reliable screening tool for OSA in people with DS that bypasses the need for laboratory-based polysomnography (sleep studies) was not achieved. This work, importantly, indicates that patients with DS should continue to be monitored for OSA according to current healthcare guidelines.

Genome editing technologies capable of generating large sequence insertions would obviate the need to develop custom patient-specific approaches, enabling the treatment of larger swaths of patients with diverse mutations using a single therapeutic. Towards this goal, CGM Investigators led by Ben Kleinstiver recently developed several engineered versions of CRISPR-associated transposases (CASTs) with improved properties that can insert large kilobase-scale DNA cargos into genomes. We engineered CAST enzymes that have dramatically improved safety by reducing their off-target genome-wide integrations, that have enhanced insertion purity and efficiency, and that function for the first time in human cells, positioning CASTs as a leading technology for kilobase-scale genome edits for a new class of genetic medicines.

Nature picks the top seven tools and techniques that they feel are positioned to have the greatest scientific impact in 2023, among them being the CRSPR-Cas9 work being done in CGM, Ben Kleinstiver‘s lab. This is an important honor not only for his lab, but his technician leading the project, Russell Walton.

People with the same body-mass index (BMI) can have different distributions of body fat, which could affect heart and metabolic disease risk. To look for associations between fat distribution and disease risk, CGM PI, Amit Khera, and colleagues used deep learning models to analyze whole-body MRI images of more than 40,000 people from the UK Biobank and quantify fat volumes at three anatomical locations. Using these data, they found an association between deep belly fat and increased risk of type 2 diabetes and coronary artery disease in people with the same BMI, as well as a link between hip and thigh fat and reduced disease risk. The study shows how fat distribution can affect disease risk independent of BMI.