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Lung Function Linked to Locus Moderated by Smoking Exposure, Methylation in Urban Children

For a paper appearing in PLOS Genetics, researchers at the University of Chicago and other centers describe early lung function impairment-linked features found in children living in urban environments. Starting with a genome-wide association study that included more than 1,000 children from low-income, urban neighborhoods, the team narrowed in on a chromosome 14 locus encompassing the TDRD9 gene that tracked with a lung function measurement known as "percent predicted forced expiratory volume in one second" (FEV1). That association, in turn, appeared to be moderated by tobacco smoke exposure-related DNA methylation levels at the locus in airway cells in a series of subsequent Mendelian randomization and mediation analyses. Together, these and other findings point to "a potential mechanism through which genetic risk and environmental exposures can affect airway development," the authors say, "perhaps leading to interventions that can help reduce the burden of asthma in socioeconomically disadvantaged children."