Progress To investigate the effects of genetic and environmental factors, and their interactions, on respiratory health in adults we have established several high-quality population resources. We have been working with the extramurally funded cohort, the Atherosclerosis Risk in Communities (ARIC) study to examine both genetic and environmental factors in adult respiratory health. The ARIC study is a cohort of 16,000 adults assembled from 1987-1989 in four US communities. ARIC has a wealth of detailed cardiovascular and respiratory phenotypes. We have used the genome wide association genotyping in ARIC to look for novel genes associated with pulmonary function and chronic obstructive pulmonary disease (COPD). In 2009, we formed a pulmonary function analysis group within the CHARGE consortium (Cohorts for Heart and Aging Research in Genomic Epidemiology) which includes several other cohorts with genome wide association genotyping and pulmonary function data (Hancock et al. Nat Genet 2009). In our CHARGE meta-analysis, we identified eight novel loci related to pulmonary function. All but one have now been replicated by other groups. We subsequently developed a collaborated with a European consortium (SpiroMeta) to expand our work. We have published joint consortium papers on pulmonary function (Soler Artigas et al. Nat Genet 2011) and COPD (Wilk et al. AJRCCM 2012). In the past year we published one of the first papers incorporating interaction into genome wide association studies. In so doing we identified 3 additional novel loci for pulmonary function. We have submitted a paper on genome wide analysis of longitudinal change in pulmonary function. We have also taken the lead on a paper using targeted sequencing to follow-up on two of our GWAS hits. We are also evaluating the role of rare variants using exome chip data. Over the past several years, I have been collaborating with Jane Hoppin and others at NIEHS and NCI to examine agricultural factors in relation to asthma and COPD phenotypes in the Agricultural Health Study (AHS), a large cohort of farmers and their spouses in Iowa and North Carolina. To date, we have had a number of interesting findings based on very simple questionnaire outcomes. We continued to expand these observations in new papers this year. To follow-up on these observations, we are doing a new studywhich is described in a separate annual report - ES102385-01. Another population is the NIEHS Sister Study. This NIEHS cohort has enrolled 50,000 sisters of women with breast cancer. I have added nonmalignant respiratory disease questions to the questionnaire with the aim of examining gene-environment interaction in relation to respiratory disease in this cohort as it matures. The cohort is being followed up annually. We are analyzing air pollution in relation to development of wheeze and asthma.

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Mirabelli, Maria C; Preisser, John S; Loehr, Laura R et al. (2016) Lung function decline over 25 years of follow-up among black and white adults in the ARIC study cohort. Respir Med 113:57-64
Croteau-Chonka, Damien C; Qiu, Weiliang; Martinez, Fernando D et al. (2016) Gene Expression Profiling in Blood Provides Reproducible Molecular Insights into Asthma Control. Am J Respir Crit Care Med :
Hoppin, Jane A; Umbach, David M; Long, Stuart et al. (2016) Pesticides Are Associated with Allergic and Non-Allergic Wheeze among Male Farmers. Environ Health Perspect :
Bennett, William D; Ivins, Sally; Alexis, Neil E et al. (2016) Effect of Obesity on Acute Ozone-Induced Changes in Airway Function, Reactivity, and Inflammation in Adult Females. PLoS One 11:e0160030
House, John S; Li, Huiling; DeGraff, Laura M et al. (2015) Genetic variation in HTR4 and lung function: GWAS follow-up in mouse. FASEB J 29:323-35
(2015) Directional dominance on stature and cognition in diverse human populations. Nature 523:459-62
Hernández-Cadena, Leticia; Zeldin, Darryl C; Barraza-Villarreal, Albino et al. (2015) Indoor determinants of dustborne allergens in Mexican homes. Allergy Asthma Proc 36:130-7
Sharma, Sunita; Kho, Alvin T; Chhabra, Divya et al. (2015) Glucocorticoid genes and the developmental origins of asthma susceptibility and treatment response. Am J Respir Cell Mol Biol 52:543-53
Obeidat, Ma'en; Hao, Ke; Bossé, Yohan et al. (2015) Molecular mechanisms underlying variations in lung function: a systems genetics analysis. Lancet Respir Med 3:782-95
Chan, Stephanie H; Van Hee, Victor C; Bergen, Silas et al. (2015) Long-Term Air Pollution Exposure and Blood Pressure in the Sister Study. Environ Health Perspect 123:951-8

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