Study examines how environment and genetics together shape the health of children with asthma

ALOFT study investigators include Francesca Luca, Ph.D.; Samuele Zilioli, Ph.D.; and Roger Pique-Regi, Ph.D.

The National Institutes of Health has awarded a trio of researchers from Wayne State University’s School of Medicine and College of Liberal Arts and Sciences a five-year, $2.2 million grant to expand a project started eight years ago in the Detroit metro area, which studies how family lifestyle and environment can exacerbate genetic predisposition to asthma.

Professor of Molecular Medicine and Genetics Francesca Luca, Ph.D.; Assistant Professor of Psychology and Family Medicine and Public Health Sciences Samuele Zilioli, Ph.D.; and Associate Professor of Molecular Medicine and Genetics Roger Pique-Regi, Ph.D., are the principal investigators of “Psychosocial and Genetic Effects on Gene Expression and Asthma,” a project launched in March with support from the National Heart, Lung and NIH Blood Institute.

The NHLBI has also supported the study, Asthma in the Lives Of Families Today, or ALOFT, through two previous grants. A total of 297 children were recruited for the first ALOFT studies. The researchers plan to recruit 200 new families with two children per family aged 10 to 15 at the time of recruitment.

Preliminary results from bulk RNA sequencing analysis in peripheral leukocytes demonstrated that psychosocial factors are associated with transcriptional changes for a large number of genes, many of which are involved in immunological functions.

“Importantly, we and others have discovered an important role for blood cell type composition in interindividual variation in response to psychosocial environments and their effects on immunological health and asthma symptoms,” said Dr. Luca.

The results of the cohort’s initial studies, “Psychosocial experiences modulate asthma-associated genes through the gene environment,” are published in eLife, an open-access online platform.

“With this new grant in particular, we are trying to disentangle the genetic and environmental components by studying siblings where only one has asthma and the other is healthy. We are also focusing on individual cell types in the blood, rather than looking at all cell types together,” Dr Luca added.

Specifically, they will use the grant to unravel the contribution of psychosocial factors and asthmatic status to patterns of transcriptional dysregulation; study the effects of psychosocial factors on the regulation of transcription in subpopulations of blood cell types; and to determine the role of genetic variation in modulating these effects and their consequences for the health of children with asthma.

The team plans to use a combination of bulk and single-cell RNA sequencing on immune cells collected from children with asthma and their asymptomatic siblings. “The complementary expertise of our team will uncover specific genetic and psychosocial factors associated with an increased risk of poor physical health and well-being,” said Dr. Luca.

The findings could guide personalized medical and behavioral interventions to lessen disease severity in children with asthma.

“I don’t think there are many people doing social genomics at this level of detail among young African Americans with asthma,” he said. “Asthma is one of the costliest pediatric health problems. Poor cities in the United States, including Detroit, suffer a disproportionate burden of asthma-related morbidity and mortality.

The grant number for this study from the National Institutes of Health is 1R01HL162574-01.

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