Research Recap: May 9 - 20
A biweekly overview of recent studies published by Institute investigators and their collaborators spans a wide variety of topics, including:
Parental attitudes toward Standard Newborn Screening and Newborn Genomic Sequencing; Association between GLP-1RAs and the risk of biliary-related diseases in patients with type 2 diabetes; Recommendations to modify infection control precautions in the light of the COVID-19 pandemic; Prediction properties of neural network models; and Association of pollution exposure with adolescent lung function.
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The importance of parents’ perspectives in the decision to integrate Newborn Genomic Sequencing into Standard Newborn Screening
With increasing utility and decreasing cost of genomic sequencing, augmentation of standard newborn screening (NBS) programs with newborn genomic sequencing (nGS) has been proposed. However, parents' perspectives must be considered before integrating nGS into newborn screening. A team of investigators including Kurt Christensen used data from surveys administered to parents of healthy newborns who were enrolled in the BabySeq Project to better understand parental attitudes toward population based NBS and nGS. Their paper, published in Frontiers in Genetics, reports higher support among parents for every newborn receiving standard NBS than for nGS, but most parents reported being very interested in receiving information on their baby's risk of developing a disease in childhood or adulthood that can be prevented, treated, or cured. Authors note that parents' opinions are crucial to inform design and delivery of public health programs, as the success of the program hinges on parents' trust and participation. They propose that an optional add-on consent to nGS may be a feasible approach that would not affect the current high participation rates in NBS.
Institute Investigator(s): Kurt Christensen
Association between glucagon-like peptide-1 receptor agonists and the risk of biliary-related diseases in patients with type 2 diabetes
Clinical trials have suggested that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may be associated with a higher risk of biliary-related diseases in patients with type 2 diabetes but limited real-world studies have examined the comparative biliary safety of GLP-1RAs versus other antihyperglycemic drugs. A team of investigators, including senior author Darren Toh, estimated the comparative risk of biliary-related diseases between GLP-1RAs and sodium glucose cotransporter 2 inhibitors (SGLT2is) through a retrospective cohort study using data from the Taiwan National Health Insurance Database. Findings, published in Pharmacotherapy, report that GLP-1RA use was associated with a numerically higher risk of biliary-related diseases versus SGLT2i use in an on-treatment analysis. Additionally, the increased risk of the composite outcome associated with GLP-1RAs was more evident in patients aged over 60 years, women, and 120 days after treatment initiation. Based on their findings, authors conclude that GLP-1RAs might be associated with an elevated risk of biliary-related diseases compared to SGLT2is in Asian patients with type 2 diabetes.
Institute Investigator(s): Darren Toh
How the COVID-19 pandemic revealed an urgent need to modify and unify infection control guidelines
The COVID-19 pandemic has shone an intense spotlight on respiratory precautions for healthcare workers managing patients with respiratory viral infections. In an editorial published in the Journal of Infectious Diseases, investigators Michael Klompas and Chanu Rhee discuss the personal protective equipment recommendations issued by the U.S. Centers for Disease Control and Prevention and importantly, question the suitability of the specific studies that seem to be the basis for the CDC’s recommendations. Authors describe the impossibility of reconciling the CDC’s legacy recommendations with the wealth of data now demonstrating the primacy of the respiratory route in respiratory viral transmission and the protective nature of distance against both aerosol-borne and droplet-borne pathogens. Future studies comparing N95 respirators versus surgical masks are encouraged, as are recommendations to require providers to wear their assigned face covering during all patient interactions when community infection rates are high, regardless of patients’ symptoms, and to incorporate epidemiologic analyses or whole genome sequencing to exclude community-acquired infections. Finally, authors recommend modifying infection control guidelines for respiratory viruses and switching to a universal set of respiratory viral precautions that includes wearing gowns, gloves, eye protection, and fitted respirators in well-ventilated spaces.
An evaluation of the prediction properties of neural network models compared to standard regression approaches
To increase power and minimize bias in statistical analyses, quantitative outcomes are often adjusted for precision and confounding variables using standard regression approaches. The outcome is modeled as a linear function of the precision variables and confounders, but for many complex phenotypes the assumptions of the linear regression models are not always met. A team of investigators including Ann Wu and senior author Sharon Lutz, evaluated the prediction properties of neural network models as compared to standard regression models using data from the UK Biobank, the COPDGene study, and the Childhood Asthma Management Program (CAMP) to assess the performance of both approaches. Results, published in PLoS One, suggest that neural network models have an advantage over standard regression approaches when the phenotypic distribution is skewed, but when the distribution is not skewed, the approaches performed similarly. These findings are relevant to studies that analyze phenotypes that are skewed by nature or where the phenotype of interest is skewed as a result of the ascertainment condition. Researchers recommend that future studies examine whether the covariate adjustment using neural networks improves the performance of genome wide association studies for rare or common variants.
Examining the association of pollution exposures at different time points with adolescent lung function
Long-term ambient air pollution exposure has been associated with reduced child lung function, but there is conflicting evidence as to whether early life exposure has a persistent effect on child lung function or if more recent exposures have a greater impact and improvements in air quality may reverse or attenuate these effects. Using data from Project Viva, a group of investigators including Emily Oken and Joanne Sordillo, conducted a study to evaluate the association of pollution exposures at different time points with adolescent lung function, and whether change in PM2.5 levels was associated with lung function growth. Results, published in the Annals of the American Thoracic Society, found no associations of proximity to roadway at birth or mid-childhood, PM2.5 exposure during the first year of life, or PM2.5 exposure in the prior year with adolescent lung function. However, improvement in average annual PM2.5 exposure between the mid-childhood and early adolescent visits was associated with faster lung function growth. Additionally, associations between pollution and adolescent lung function differed by sex. Living closer to a roadway as well as prior-year, since mid-childhood, and lifetime PM2.5 exposure were negatively associated with lung function for boys but were null among girls. Authors conclude that more recent air pollution exposures may have a greater effect on adolescent lung function than early life exposure, and improving air quality, even at already low air pollution levels, appears to be beneficial to adolescent respiratory health.