Parthasarathy, S., Vasquez, M. M., Halonen, M., Bootzin, R., Quan, S. F., Martinez, F. D., & Guerra, S. (2015). Persistent insomnia is associated with mortality risk. The American journal of medicine, 128(3), 268-75.e2.
Insomnia has been associated with mortality risk, but whether this association is different in subjects with persistent vs intermittent insomnia is unclear. Additionally, the role of systemic inflammation in such an association is unknown.
Guerra, S., Vasquez, M. M., Spangenberg, A., Halonen, M., & Martin, R. J. (2016). Club cell secretory protein in serum and bronchoalveolar lavage of patients with asthma. The Journal of allergy and clinical immunology, 138(3), 932-934.e1.
Guerra, S., & et al, . (2016). Health-related quality of life and risk factors associated with spirometric restriction. European Respiratory Journal.
Joubert, B. R., Felix, J. F., Yousefi, P., Bakulski, K. M., Just, A. C., Breton, C., Reese, S. E., Markunas, C. A., Richmond, R. C., Xu, C., Küpers, L. K., Oh, S. S., Hoyo, C., Gruzieva, O., Söderhäll, C., Salas, L. A., Baïz, N., Zhang, H., Lepeule, J., , Ruiz, C., et al. (2016). DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis. American journal of human genetics, 98(4), 680-96.
Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role. We formed the Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across 13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in relation to maternal smoking at genome-wide statistical significance (false discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not previously related to smoking and methylation in either newborns or adults. Several genes are relevant to diseases that can be caused by maternal smoking (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A number of differentially methylated CpGs were associated with gene expression. We observed enrichment in pathways and processes critical to development. In older children (5 cohorts, n = 3,187), 100% of CpGs gave at least nominal levels of significance, far more than expected by chance (p value 2.2 × 10(-16)). Results were robust to different normalization methods used across studies and cell type adjustment. In this large scale meta-analysis of methylation data, we identified numerous loci involved in response to maternal smoking in pregnancy with persistence into later childhood and provide insights into mechanisms underlying effects of this important exposure.
Lange, P., Celli, B., Agustí, A., Boje Jensen, G., Divo, M., Faner, R., Guerra, S., Marott, J. L., Martinez, F. D., Martinez-Camblor, P., Meek, P., Owen, C. A., Petersen, H., Pinto-Plata, V., Schnohr, P., Sood, A., Soriano, J. B., Tesfaigzi, Y., & Vestbo, J. (2015). Lung-Function Trajectories Leading to Chronic Obstructive Pulmonary Disease. The New England journal of medicine, 373(2), 111-22.
BIO5 Collaborators
Stefano Guerra, Fernando Martinez
Chronic obstructive pulmonary disease (COPD) is thought to result from an accelerated decline in forced expiratory volume in 1 second (FEV1) over time. Yet it is possible that a normal decline in FEV1 could also lead to COPD in persons whose maximally attained FEV1 is less than population norms.
