Author Interviews, Genetic Research / 21.03.2023 Interview with: Ernest Turro, PhD Associate Professor Genetics and Genomics Sciences The Turro group runs a research program on statistical genomics, with a dual focus on rare diseases and blood-related traits at the Icahn School of Medicine Mount Sinai Health System What is the background for this study? Would you describe the Rareservoir database? Response:   The main motivation for our work is that only half of the approximately 10,000 catalogued rare diseases have a resolved genetic cause (or aetiology). Patients with these diseases are unable to obtain a genetic diagnosis which could otherwise inform prognosis, treatment for themselves and affected relatives. One route towards resolving the remaining aetiologies is to enroll large numbers of rare disease patients into research studies so that statistical analyses can be performed comparing the genetic with the clinical characteristics of the study participants. One major endeavour, the 100,000 Genomes Project (100KGP), sequenced the genomes and collected clinical phenotype data for 34,523 UK patients and 43,016 unaffected relatives across 29,741 families. The scale of this study is unprecedented, partly thanks to the ever-decreasing cost of DNA sequencing (25 years ago, it cost $1bn to sequence a whole genome, while now it costs only a few hundred dollars). Working with such large datasets is notoriously cumbersome. To overcome this, we developed a computational approach (the Rareservoir) that distills the most important information into a relatively small database, allowing us to apply our statistical methods nimbly. We noted that the "genetic variants" that cause rare diseases are typically kept rare in the human population by natural selection because affected individuals tend to have few children, if any. This meant that we could discard the genetic information corresponding to variants that are common in the human population without throwing away the key disease-causing variants. By focussing on these "rare variants", we were able to perform our analyses using a small database (a `Rareservoir’), only 5.5GB in size, hastening our progress significantly. (more…)
Author Interviews, Infections, NIH / 30.06.2022 Interview with: Nihal Altan-Bonnet, Ph.D. Chief of the Laboratory of Host-Pathogen Dynamics NHLBI  What is the background for this study?  What are the main findings? Response: Enteric viruses such as norovirus, rotavirus and astrovirus are responsible for nearly 1.5 billion global infections per year resulting in gastrointestinal illnesses and sometimes leading to death in the very young, in the elderly and in the immunocompromised. These viruses have been thought to traditionally infect and replicate only in the intestines, then shed into feces and transmit to others via the oral-fecal route (e.g. through ingestion of fecal contaminated food items). Our findings reported in Nature, using animal models of norovirus, rotavirus and astrovirus infection, challenge this traditional view and reveal that these viruses can also replicate robustly in salivary glands, be shed into saliva in large quantities and transmit through saliva to other animals. In particular we also show infected infants can transmit these viruses to their mothers mammary glands via suckling and this leads to both an infection in their mothers mammary glands but also a rapid immune response by the mother resulting in a surge in her milk antibodies. These milk antibodies may play a role in fighting the infection in their infants .  (more…)
AHA Journals, Author Interviews, Blood Pressure - Hypertension, University of Pennsylvania / 09.09.2019 Interview with: Jordana Cohen, MD, MSCE Assistant Professor of Medicine and Epidemiology Renal-Electrolyte and Hypertension Division Center for Clinical Epidemiology and Biostatistics Perelman School of Medicine University of Pennsylvania What is the background for this study? Response: In the June 18, 2019 issue of Annals of Internal Medicine, we published a systematic review and meta-analysis evaluating the cardiovascular risks of white coat hypertension (WCH; i.e. elevated office blood pressure and normal out-of-office blood pressure). The goal of the meta-analysis was to clarify previous mixed results regarding the risks of untreated WCH and treated WCH. The meta-analysis examined 27 studies – including 64,273 patients – and demonstrated that untreated WCH is associated with an increased risk of cardiovascular events (36%), all-cause mortality (33%), and cardiovascular mortality (109%) compared to normotension. This risk was strongest in studies with a mean age ≥55 years or that included participants with cardiac risk factors, such as diabetes and chronic kidney disease. We found no increased cardiovascular risk associated with treated white coat hypertension. (more…)