<p><strong>Objective</strong>: Individual socioeconomic status (SES) has been associated with asthma incidence but whether neighborhood<br />SES has an influence is unknown. We assessed the contributions of neighborhood socioeconomic status (SES), neighborhood housing density, neighborhood racial composition, and individual SES to the development of adult-onset asthma in Black<br />women, accounting for other known or suspected risk factors.<br /><strong></strong></p><p><strong>Design and Participants</strong>: Prospective cohort study conducted among 47,779 African American women followed with biennial health questionnaires from 1995 to 2011.<br /><strong></strong></p><p><strong>Methods and Main Outcome Measures</strong>: Incident asthma was defined as new selfreport of doctor-diagnosed asthma with<br />concurrent use of asthma medication. We assessed neighborhood SES, indicated by census variables representing income,<br />education, and wealth, and housing density and % African American population, as well as individual SES, indicated by highest education of participant/spouse. Cox proportional hazards models were used to derive multivariable hazard ratios (HRs) and<br />95% CIs for the association of individual SES and neighborhood variables with asthma incidence.<br /><strong></strong></p><p><strong>Results</strong>: During a 16-year follow-up period, 1520 women reported incident asthma. Neighborhood factors were not associated<br />with asthma incidence after control for individual SES, body mass index, and other factors. Compared with college graduates,<br />the multivariable HR for asthma was 1.13 (95% CI 1.00-1.28) for women with some college education and 1.23 (95% CI 1.05-<br />1.44) for women with no more than a high school education.<br /><strong></strong></p><p><strong>Conclusions</strong>: Individual SES, but not neighborhood SES or other neighborhood factors, was associated with the incidence<br />of adult-onset asthma in this population of African American women. <em>Ethn Dis</em>. 2016;26(1):113-122; doi:10.18865/<br />ed.26.1.113</p><p> </p>
Publisher's version (útgefin grein) ; Rationale: Idiopathic pulmonary fibrosis (IPF) is a complex lung disease characterized by scarring of the lung that is believed to result from an atypical response to injury of the epithelium. Genome-wide association studies have reported signals of association implicating multiple pathways including host defense, telomere maintenance, signaling, and cell-cell adhesion. Objectives: To improve our understanding of factors that increase IPF susceptibility by identifying previously unreported genetic associations. Methods: We conducted genome-wide analyses across three independent studies and meta-analyzed these results to generate the largest genome-wide association study of IPF to date (2,668 IPF cases and 8,591 controls). We performed replication in two independent studies (1,456 IPF cases and 11,874 controls) and functional analyses (including statistical fine-mapping, investigations into gene expression, and testing for enrichment of IPF susceptibility signals in regulatory regions) to determine putatively causal genes. Polygenic risk scores were used to assess the collective effect of variants not reported as associated with IPF. Measurements and Main Results: We identified and replicated threenewgenome-wide significant (P<5×10-8) signals of association with IPF susceptibility (associated with altered gene expression of KIF15, MAD1L1, and DEPTOR) and confirmed associations at 11 previously reported loci. Polygenic risk score analyses showed that the combined effect of many thousands of as yet unreported IPF susceptibility variants contribute to IPF susceptibility. Conclusions: The observation that decreased DEPTOR expression associates with increased susceptibility to IPF supports recent studies demonstrating the importance of mTOR signaling in lung fibrosis. New signals of association implicating KIF15 and MAD1L1 suggest a possible role of mitotic spindle-assembly genes in IPF susceptibility. ; R.J.A. is an Action for Pulmonary Fibrosis Research Fellow. L.V.W. holds a GSK/British Lung Foundation Chair in Respiratory Research. R.G.J. is supported by a National Institute for Health Research (NIHR) Research Professorship (NIHR reference RP-2017-08-ST2-014). I.N. is supported by the NHLBI (R01HL130796). B.G.-G. is funded by Agencia Canaria de Investigación, Innovación y Sociedad de la Información (TESIS2015010057) cofunded by European Social Fund. J.M.O. is supported by the NHLBI (K23HL138190). C.F. is supported by the Spanish Ministry of Science, Innovation and Universities (grant RTC-2017-6471-1; Ministerio de Ciencia e Innovacion/Agencia Estatal de Investigación/Fondo Europeo de Desarrollo Regional, Unión Europea) cofinanced by the European Regional Development Funds "A way of making Europe" from the European Union and by agreement OA17/008 with Instituto Tecnológico y de Energías Renovables to strengthen scientific and technological education, training, research, development and innovation in Genomics, Personalized Medicine and Biotechnology. The Spain Biobank array genotyping service was performed at CEGEN-PRB3-ISCIII, which is supported by PT17/0019, of the PE I+D+i 2013–2016, funded by Instituto de Salud Carlos III, and cofinanced by the European Regional Development Funds. P.L.M. is an Action for Pulmonary Fibrosis Research Fellow. M.O. is a fellow of the Parker B. Francis Foundation and a Scholar of the Michael Smith Foundation for Health Research. B.D.H. is supported by NIH K08 HL136928, Parker B. Francis Research Opportunity Award. M.H.C. and G.M.H. are supported by NHLBI grants R01HL113264 (M.H.C.), R01HL137927 (M.H.C.), R01HL135142 (M.H.C. and G.M.H.), R01111024 (G.M.H.), and R01130974 (G.M.H.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The funding body has no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript. T.M.M. is supported by an NIHR Clinician Scientist Fellowship (NIHR Ref: CS-2013-13-017) and a British Lung Foundation Chair in Respiratory Research (C17-3). M.D.T. is supported by a Wellcome Trust Investigator Award (WT202849/Z/16/Z). The research was partially supported by the NIHR Leicester Biomedical Research Centre; the views expressed are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR, or the Department of Health. I.P.H. was partially supported by the NIHR Nottingham Biomedical Research Centre; the views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. I.S. is supported by Medical Research Council (G1000861) and Asthma UK (AUK-PG-2013-188). D.F. was supported by an Intermediate Fellowship from the Wellcome Trust (097152/Z/11/Z). This work was partially supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre. V.N. is funded by an NIHR Clinical Lectureship. G.G. is supported by project grant 141513-051 from the Icelandic Research Fund and Landspitali Scientific Fund A-2016-023, A-2017-029, and A-2018-025. D.J.L. and A.M. are supported by Multi-Ethnic Study of Atherosclerosis (MESA) and the MESA SNP Health Association Resource (SHARe) project are conducted and supported by the NHLBI in collaboration with MESA investigators. Support for MESA is provided by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, UL1-TR-001881, and DK063491. Funding for SHARe genotyping was provided by NHLBI Contract N02-HL-64278. Genotyping was performed at Affymetrix (Santa Clara, California) and the Broad Institute of Harvard and Massachusetts Institute of Technology (Boston, Massachusetts) using the Affymetrix Genome-Wide Human SNP Array 6.0. This work was supported by NIH grants R01 HL131565 (A.M.), R01 HL103676 (D.J.L.), and R01 HL137234 (D.J.L.). ; Peer Reviewed
