Melbourne School of Population and Global Health - Research Publications
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ItemNo Preview AvailableMeta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis(NATURE PUBLISHING GROUP, 2012-02)Atopic dermatitis (AD) is a commonly occurring chronic skin disease with high heritability. Apart from filaggrin (FLG), the genes influencing atopic dermatitis are largely unknown. We conducted a genome-wide association meta-analysis of 5,606 affected individuals and 20,565 controls from 16 population-based cohorts and then examined the ten most strongly associated new susceptibility loci in an additional 5,419 affected individuals and 19,833 controls from 14 studies. Three SNPs reached genome-wide significance in the discovery and replication cohorts combined, including rs479844 upstream of OVOL1 (odds ratio (OR) = 0.88, P = 1.1 × 10(-13)) and rs2164983 near ACTL9 (OR = 1.16, P = 7.1 × 10(-9)), both of which are near genes that have been implicated in epidermal proliferation and differentiation, as well as rs2897442 in KIF3A within the cytokine cluster at 5q31.1 (OR = 1.11, P = 3.8 × 10(-8)). We also replicated association with the FLG locus and with two recently identified association signals at 11q13.5 (rs7927894; P = 0.008) and 20q13.33 (rs6010620; P = 0.002). Our results underline the importance of both epidermal barrier function and immune dysregulation in atopic dermatitis pathogenesis.
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ItemGenome-Wide Association Studies of Asthma in Population-Based Cohorts Confirm Known and Suggested Loci and Identify an Additional Association near HLA(PUBLIC LIBRARY SCIENCE, 2012-09-28)RATIONALE: Asthma has substantial morbidity and mortality and a strong genetic component, but identification of genetic risk factors is limited by availability of suitable studies. OBJECTIVES: To test if population-based cohorts with self-reported physician-diagnosed asthma and genome-wide association (GWA) data could be used to validate known associations with asthma and identify novel associations. METHODS: The APCAT (Analysis in Population-based Cohorts of Asthma Traits) consortium consists of 1,716 individuals with asthma and 16,888 healthy controls from six European-descent population-based cohorts. We examined associations in APCAT of thirteen variants previously reported as genome-wide significant (P<5 x 10(-8)) and three variants reported as suggestive (P<5× 10(-7)). We also searched for novel associations in APCAT (Stage 1) and followed-up the most promising variants in 4,035 asthmatics and 11,251 healthy controls (Stage 2). Finally, we conducted the first genome-wide screen for interactions with smoking or hay fever. MAIN RESULTS: We observed association in the same direction for all thirteen previously reported variants and nominally replicated ten of them. One variant that was previously suggestive, rs11071559 in RORA, now reaches genome-wide significance when combined with our data (P = 2.4 × 10(-9)). We also identified two genome-wide significant associations: rs13408661 near IL1RL1/IL18R1 (P(Stage1+Stage2) = 1.1x10(-9)), which is correlated with a variant recently shown to be associated with asthma (rs3771180), and rs9268516 in the HLA region (P(Stage1+Stage2) = 1.1x10(-8)), which appears to be independent of previously reported associations in this locus. Finally, we found no strong evidence for gene-environment interactions with smoking or hay fever status. CONCLUSIONS: Population-based cohorts with simple asthma phenotypes represent a valuable and largely untapped resource for genetic studies of asthma.
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ItemA review of the impact of occupational contact dermatitis on quality of life.(Hindawi Limited, 2011)Occupational contact dermatitis (OCD) is the most common occupational skin disease in many countries. We reviewed the current evidence on how OCD impacts on quality of life (QoL). The three commonly used QoL questionnaires in OCD were the Short-Form Health Survey (SF-36), the Dermatology Life Quality Index (DLQI), and the Skindex. Despite the availability of a variety of validated QoL instruments, none of them is specific to OCD or entirely adequate in capturing the impact of OCD on QoL. Nonetheless, the results of this paper do suggest a significant impact. Use of QoL measures in clinical settings will provide patients with an opportunity to express their concerns and assist clinicians to evaluate the effectiveness of management beyond the clinical outcomes. This paper also highlights the lack of a disease-specific QOL instrument and the importance of developing a validated measure to assess QOL in OCD, enabling comparison across countries and occupational groups.
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ItemAre Australian immigrants at a risk of being physically inactive?(BIOMED CENTRAL LTD, 2011-06-01)BACKGROUND: We examined whether physical activity risk differed between migrant sub-groups and the Australian-born population. METHODS: Data were drawn from the Australian National Health Survey (2001) and each resident's country of birth was classified into one of 13 regions. Data were gathered on each resident's physical activity level in the fortnight preceding the survey. Multivariable logistic regression, adjusted for potential confounders examined the risk of physical inactivity of participants from each of the 13 regions compared to the Australian-born population. RESULTS: There was a greater prevalence of physical inactivity for female immigrants from most regions compared to male immigrants from a like region. Immigrants from South East Asia (OR 2.04% 95% CI 1.63, 2.56), Other Asia (OR 1.53 95% CI 1.10, 2.13), Other Oceania (1.81 95% CI 1.11, 2.95), the Middle East (OR 1.42 95% CI 0.97, 2.06 [note: border line significance]) and Southern & Eastern Europe are at a significantly higher risk of being physically inactive compared to those born in Australian. In contrast, immigrants from New Zealand (OR 0.77 95% CI 0.62, 0.94), the UK & Ireland (OR 0.82 95% CI 0.73, 0.92), and other Africa (OR 0.69 95% CI 0.51, 0.94) are at a significantly lower risk of being physically inactive compared to the Australian born population. CONCLUSION: Future research identifying potential barriers and facilitators to participation in physical activity will inform culturally sensitive physical activity programs that aim to encourage members of specific regional ethnic sub-groups to undertake physical activity.
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ItemLatitude, birth date, and allergy(PUBLIC LIBRARY SCIENCE, 2005-10)BACKGROUND: The space and time distribution of risk factors for allergic diseases may provide insights into disease mechanisms. Allergy is believed to vary by month of birth, but multinational studies taking into account latitude have not been conducted. METHODS AND FINDINGS: A questionnaire was distributed in 54 centres to a representative sample of 20- to 44-y-old men and women mainly in Europe but also including regions in North Africa, India, North America, Australia, and New Zealand. Data from 200,682 participants were analyzed. The median prevalence of allergic rhinitis was 22%, with a substantial variation across centres. Overall, allergic rhinitis decreased with geographical latitude, but there were many exceptions. No increase in prevalence during certain winters could be observed. Also, no altered risk by birth month was found, except borderline reduced risks in September and October. Effect estimates obtained by a multivariate analysis of total and specific IgE values in 18,085 individuals also excluded major birth month effects and confirmed the independent effect of language grouping. CONCLUSION: Neither time point of first exposure to certain allergens nor early infections during winter months seems to be a major factor for adult allergy. Although there might be effects of climate or environmental UV exposure by latitude, influences within language groups seem to be more important, reflecting so far unknown genetic or cultural risk factors.
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ItemAn interactive workshop plus locally adapted guidelines can improve General Practitioners asthma management and knowledge: A cluster randomised trial in the Australian setting(BMC, 2008-04-20)BACKGROUND: A cluster randomised trial was conducted to determine the effectiveness of locally adapted practice guidelines and education about paediatric asthma management, delivered to general practitioners (GPs) in small group interactive workshops. METHODS: Twenty-nine practices were randomly allocated to one of three study arms. Australian asthma management guidelines were adapted to accommodate characteristics of the local area. GPs in the intervention arm (Group 1, n = 18 GPs) participated in a small group based education program and were provided with the adapted guidelines. One control arm (Group 2, n = 18 GPs) received only the adapted guidelines, while the other control arm (Group 3, n = 15 GPs) received an unrelated education intervention. GPs' knowledge, attitudes and management of paediatric asthma was assessed. RESULTS: Post intervention, intervention arm GPs were no more likely to provide a written asthma action plan, but were better able to assess the severity of asthma attack (Group 1vs Group 2 p = 0.05 and Group 1 vs Group 3 p = 0.01), better able to identify patients at high risk of severe attack (Group 1vs Group 3 p = 0.06), and tended to score higher on the asthma knowledge questionnaire (Group 1 vs Group 2 p = 0.06 and Group 1 vs Group 3 p = 0.2). Most intervention arm GPs felt more confident than control GPs to manage acute asthma attack and ongoing management of infrequent episodic asthma. CONCLUSION: Using interactive small group workshops to disseminate locally adapted guidelines was associated with improvement in GP's knowledge and confidence to manage asthma, but did not change GP's self-reported provision of written action plans.
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ItemNo Preview AvailableAuthors' reply [11]( 2007-10-01)
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ItemAnaphylaxis to Skin Prick Testing in a 29-Year-Old Woman(Scientific Research Publishing, Inc., 2012)
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ItemNo Preview AvailableHouse dust mite sensitization in toddlers predicts current wheeze at age 12 years(MOSBY-ELSEVIER, 2011-10)BACKGROUND: Identification of children at risk of developing asthma provides a window of opportunity for risk-reducing interventions. Allergen sensitization might identify high-risk children. OBJECTIVE: We sought to determine whether skin prick tests (SPTs) to individual allergens up to age 2 years predict wheeze at age 12 years. METHODS: In a birth cohort of 620 children oversampled for familial allergy, sensitization was assessed by using SPTs (monosensitized, polysensitized, or either) to 6 allergens at ages 6, 12, and 24 months. Wheeze and eczema were recorded 18 times during the first 2 years. Current wheeze was recorded at age 12 years. Adjusted associations were evaluated by multiple logistic regression. RESULTS: A positive SPT to house dust mite (HDM) at age 1 or 2 years predicted wheeze at age 12 years (adjusted odds ratio: 1 year, 3.31 [95% CI 1.59-6.91]; 2 years, 6.37 [95% CI, 3.48-11.66]). Among wheezy 1-year-olds, those who were HDM sensitized had a 75% (95% CI, 51% to 91%) probability of wheeze at age 12 years compared with a 36% (95% CI, 23% to 50%) probability among those not sensitized. Among eczematous 1-year-olds, those who were HDM sensitized had a 67% (95% CI, 45% to 84%) probability of wheeze at age 12 years compared with a 35% (95% CI, 25% to 45%) probability among those not sensitized. Among 1-year-old children with both eczema and wheeze, the probability of wheeze at age 12 years was 64% (95% CI, 35% to 87%) if HDM sensitized and 50% (95% CI, 26% to 74%) if not. CONCLUSION: HDM sensitization at age 1 or 2 years in wheezing and eczematous children at increased familial allergy risk predicts asthma and may inform management of these high-risk groups.
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ItemNo Preview AvailableChecking Zero Calibration of the HypAir FeNO(AMER THORACIC SOC, 2010-09-01)