Overlap of Genetic Risk between Interstitial Lung Abnormalities and Idiopathic Pulmonary Fibrosis

Rationale: Interstitial lung abnormalities (ILAs) are associated with the highest genetic risk locus for idiopathic pulmonary fibrosis (IPF); however, the extent to which there are unique associations among individuals with ILAs or additional overlap with IPF is not known.Objectives: To perform a genome-wide association study (GWAS) of ILAs.Methods: ILAs and a subpleural-predominant subtype were assessed on chest computed tomography (CT) scans in the AGES (Age Gene/Environment Susceptibility), COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease [COPD]), Framingham Heart, ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points), MESA (Multi-Ethnic Study of Atherosclerosis), and SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) studies. We performed a GWAS of ILAs in each cohort and combined the results using a meta-analysis. We assessed for overlapping associations in independent GWASs of IPF.Measurements and Main Results: Genome-wide genotyping data were available for 1,699 individuals with ILAs and 10,274 control subjects. The MUC5B (mucin 5B) promoter variant rs35705950 was significantly associated with both ILAs (P = 2.6 × 10-27) and subpleural ILAs (P = 1.6 × 10-29). We discovered novel genome-wide associations near IPO11 (rs6886640, P = 3.8 × 10-8) and FCF1P3 (rs73199442, P = 4.8 × 10-8) with ILAs, and near HTRE1 (rs7744971, P = 4.2 × 10-8) with subpleural-predominant ILAs. These novel associations were not associated with IPF. Among 12 previously reported IPF GWAS loci, five (DPP9, DSP, FAM13A, IVD, and MUC5B) were significantly associated (P < 0.05/12) with ILAs.Conclusions: In a GWAS of ILAs in six studies, we confirmed the association with a MUC5B promoter variant and found strong evidence for an effect of previously described IPF loci; however, novel ILA associations were not associated with IPF. These findings highlight common genetically driven biologic pathways between ILAs and IPF, and also suggest distinct ones

The merit of condition score and fat score as alternatives to liveweight for managing the nutrition of ewes

The liveweight profile of Merino ewes is related to the production and profitability of the sheep enterprise, but few producers measure liveweight to manage the nutrition of Merino ewes. In this paper we examine the relationship between changes in liveweight and condition score using data from the Lifetimewool project and compare condition score and fat score as alternative monitoring tools. Analyses of liveweight and condition score data from 15 flocks of Merino ewes representing a range of different genotypes and environments showed that the relationship between change in liveweight and condition score was on average 9.2 kg per unit change in condition score or 0.19 times the standard reference weight of the flock. In two experiments experienced operators were used to estimate the condition score and fat score in over 200 ewes and accredited ultrasound scanners measured the eye muscle and fat depth at the C site in the same ewes. All assessments were repeated several times in random order. Within 24 h of the assessments the sheep were slaughtered at local abattoirs where the tissue depth at the GR site was measured on the hot carcasses. Both condition score and fat score were highly repeatable though subject to operator bias. They were related to each other and to the objective measures of fat and eye muscle depth at the C site. However, 95% of sheep below condition score 2.5 had a tissue depth (muscle and fat) at the GR site ≤3 mm, by definition equal to fat score 1. As the condition score of ewes on commercial properties often fluctuates between scores 2 and 3, and small changes in condition score within this range can have large effects on welfare and profit, we conclude that condition score is the most appropriate alternative to liveweight for managing the nutritional profile of ewes

Evaluation of the impact of Lifetimewool on sheep producers

Lifetimewool was a national project that began in 2001 to develop profitable ewe feeding and management guidelines for wool producers across southern Australia. By 2005, the project included communication and adoption activities. Rigorous communication, adoption and evaluation plans were used to maintain focus on its objectives and to measure impacts. Evaluation was an integral part of the project's development and allowed the project to gain a clear idea of its impact. The project aimed to influence at least 3000 producers nationally to change the management of their ewe flock by the adoption (or part thereof) of Lifetimewool messages and guidelines. More specifically, the project aimed to 'cross the chasm' and target producers that were deemed to be in the 'early adopter' and the 'early majority' segments. The project surveyed sheep producers, sheep industry consultants and sheep industry extension practitioners at the beginning and end of the project to gauge the change in knowledge, attitudes, skills and aspirations of wool producers over the life of the project. Results from the survey of sheep producers in 2008 indicate that the project achieved its aim. About 12% (∼3000) of sheep producers nationally have changed practice due to information received from Lifetimewool since 2005. Many other producers have been affected through their increase in knowledge, belief and skills, and market segmentation of the audience shows that the project was successful in 'crossing the chasm'. The strategies employed by the project to initiate change (i.e. using private consultants and extension professionals as a pathway to adoption, and involving producers, consultants and extension professionals in the development of the Lifetimewool key messages and tools) were validated. The survey results and analysis provided baseline data for future livestock management projects to build on producers' progress towards practice change. The present paper looks at how the Lifetimewool's evaluation plan provided a focus for and demonstrated meeting its objectives. In doing so, this paper also seeks to better understand the adoption process

On-farm paddock-scale comparisons across southern Australia confirm that increasing the nutrition of Merino ewes improves their production and the lifetime performance of their progeny

Experiments conducted by Lifetimewool at plot-scale have shown that differences in the maternal liveweight during pregnancy and lactation (liveweight profiles) of individual Merino ewes influences their wool production and reproductive rate as well as the birthweight, survival, weaning weight and lifetime wool production of their lambs in a predictable manner. This study determined whether these impacts of nutrition of the ewe on ewe and progeny performance are measurable on commercial properties across southern Australia at a paddock-scale where ewes were aggregated into flocks with a greater spread of the date of conception and where the liveweight profile of the flocks were managed based on random samples of 100 ewes and liveweight was uncorrected for fleece weight or conceptus. Eighteen paddock-scale experiments at 15 sites were conducted in cooperation with wool producers across Victoria, Western Australia, New South Wales, South Australia, and Tasmania. Each co-operator joined up to 1000 mixed aged adult Merino ewes. The flock was scanned using ultrasound at Day 50 from the start of joining to identify those ewes that conceived during the first 21 days of joining. These ewes were then split at random into two treatments and fed to achieve a target difference in liveweight of 10 kg or ∼1 condition score/fat score at lambing. The production of ewes during their year of pregnancy and following their next joining was measured as was the performance of their progeny up to their third shearing. Only the 13 paddock-scale experiments that achieved a difference in liveweight profile at lambing of at least 4 kg were included in the final analysis. In these 13 experiments, increasing the nutrition of Merino ewes during pregnancy clearly increased the clean fleece weight and fibre diameter in ewes and the survival and lifetime wool production of their lambs. In most cases the size of the effect was not significantly different to that predicted by the relationship derived using individual liveweight profiles in the plot-scale experiments. This confirms that managing average ewe liveweight or condition score/fat score profile through better nutrition will lead to predictable increases in the performance of ewes and their progeny performance under commercial conditions and validates the use of the plot-scale relationships in economic analyses