15 research outputs found

    Omega-3 fatty acids and genome-wide interaction analyses reveal DPP10-pulmonary function association

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    Rationale: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have anti-inflammatory properties that could benefit adults with comprised pulmonary health. Objective: To investigate n-3 PUFA associations with spirometric measures of pulmonary function tests (PFTs) and determine underlying genetic susceptibility. Methods: Associations of n-3 PUFA biomarkers (a-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid [DPA], and docosahexaenoic acid [DHA]) were evaluated with PFTs (FEV1, FVC, and FEV1/FVC) in meta-analyses across seven cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (N=16,134 of European or African ancestry). PFT-associated n-3 PUFAs were carried forward to genome-wide interaction analyses in the four largest cohorts (N=11,962) and replicated in one cohort (N=1,687). Cohort-specific results were combined using joint 2 degree-of-freedom (2df) meta-analyses of SNPassociations and their interactions with n-3PUFAs. Results: DPA and DHA were positively associated with FEV1 and FVC (P < 0.025), with evidence for effect modification by smoking and by sex. Genome-wide analyses identified a novel association of rs11693320-an intronic DPP10 SNP-with FVC when incorporating an interaction with DHA, and the finding was replicated (P-2df = 9.4 x 10(-9) across discovery and replication cohorts). The rs11693320-A allele (frequency, similar to 80%) was associated with lower FVC (P-SNP = 2.1 x 10(-9); beta(SNP) = 2161.0 ml), and the association was attenuated by higher DHA levels (P-SNPxDHA interaction = 2.1x10(-7); beta(SNPxDHA interaction) = 36.2 ml). Conclusions: We corroborated beneficial effects of n-3 PUFAs on pulmonary function. By modeling genome-wide n-3 PUFA interactions, we identified a novel DPP10 SNP association with FVC that was not detectable in much larger studies ignoring this interaction

    Association of Forced Vital Capacity with the Developmental Gene <i>NCOR2</i>

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    Background Forced Vital Capacity (FVC) is an important predictor of all-cause mortality in the absence of chronic respiratory conditions. Epidemiological evidence highlights the role of early life factors on adult FVC, pointing to environmental exposures and genes affecting lung development as risk factors for low FVC later in life. Although highly heritable, a small number of genes have been found associated with FVC, and we aimed at identifying further genetic variants by focusing on lung development genes. Methods Per-allele effects of 24,728 SNPs in 403 genes involved in lung development were tested in 7,749 adults from three studies (NFBC1966, ECRHS, EGEA). The most significant SNP for the top 25 genes was followed-up in 46,103 adults (CHARGE and SpiroMeta consortia) and 5,062 chi

    Genome-wide association analysis identifies six new loci associated with forced vital capacity

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    Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10−8) with FVC in or near EFEMP1, BMP6, MIR129-2–HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease

    Defining barriers and enablers for clinical pathway implementation in complex clinical settings

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    Abstract Background While clinical pathways have the potential to improve patient outcomes and reduce healthcare costs, their true impact has been limited by variable implementation strategies and suboptimal research designs. This paper explores a comprehensive set of factors perceived by emergency department staff and administrative leads to influence clinical pathway implementation within the complex and dynamic environments of community emergency department settings. Methods This descriptive, qualitative study involved emergency health professionals and administrators of 15 community hospitals across Ontario, Canada. As part of our larger cluster randomized controlled trial, each site was in the preparation phase to implement one of two clinical pathways: pediatric asthma or pediatric vomiting and diarrhea. Data were collected from three sources: (i) a mediated group discussion with site champions during the project launch meeting; (ii) a semi-structured site visit of each emergency department; and (iii) key informant interviews with an administrative lead from each hospital. The Theoretical Domains Framework (TDF) was used to guide the interviews and thematically analyze the data. Domains within each major theme were then mapped onto the COM-B model—capability, opportunity, and motivation—of the Behaviour Change Wheel. Results Seven discrete themes and 58 subthemes were identified that comprised a set of barriers and enablers relevant to the planned clinical pathway implementation. Within two themes, three distinct levels of impact emerged, namely (i) the individual health professional, (ii) the emergency department team, and (iii) the broader hospital context. The TDF domains occurring most frequently were Memory, Attention and Decision Processes, Environmental Context and Resources, Behavioural Regulation, and Reinforcement. Mapping these barriers and enablers onto the COM-B model provided an organized perspective on how these issues may be interacting. Several factors were viewed as both negative and positive across different perspectives. Two of the seven themes were limited to one component, while four involved all three components of the COM-B model. Conclusions Using a theory-based approach ensured systematic and comprehensive identification of relevant barriers and enablers to clinical pathway implementation in ED settings. The COM-B system of the Behaviour Change Wheel provided a useful perspective on how these factors might interact to effect change. Trial registration ClinicalTrials.gov, NCT01815710
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