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Contains fulltext : 292919.pdf (Publisher’s version ) (Open Access) BACKGROUND: High myopia (HM), defined as a spherical equivalent refractive error (SER) ≤ -6.00 diopters (D), is a leading cause of sight impairment, through myopic macular degeneration (MMD). We aimed to derive an improved polygenic score (PGS) for predicting children at risk of HM and to test if a PGS is predictive of MMD after accounting for SER. METHODS: The PGS was derived from genome-wide association studies in participants of UK Biobank, CREAM Consortium, and Genetic Epidemiology Research on Adult Health and Aging. MMD severity was quantified by a deep learning algorithm. Prediction of HM was quantified as the area under the receiver operating curve (AUROC). Prediction of severe MMD was assessed by logistic regression. FINDINGS: In independent samples of European, African, South Asian and East Asian ancestry, the PGS explained 19% (95% confidence interval 17-21%), 2% (1-3%), 8% (7-10%) and 6% (3-9%) of the variation in SER, respectively. The AUROC for HM in these samples was 0.78 (0.75-0.81), 0.58 (0.53-0.64), 0.71 (0.69-0.74) and 0.67 (0.62-0.72), respectively. The PGS was not associated with the risk of MMD after accounting for SER: OR = 1.07 (0.92-1.24). INTERPRETATION: Performance of the PGS approached the level required for clinical utility in Europeans but not in other ancestries. A PGS for refractive error was not predictive of MMD risk once SER was accounted for. FUNDING: Supported by the Welsh Government and Fight for Sight (24WG201).

To investigate the relationship between dietary intake of niacin (water-soluble form of vitamin BThis cross-sectional study examined the association between daily niacin intake and RNFL thickness in three large population-based cohorts with varied age differences. RNFL thickness was extracted from optical coherence tomography data; energy-adjusted niacin intake was estimated from food frequency questionnaires. Linear mixed-effects models were utilised to examine the association between RNFL thickness and energy-adjusted niacin intake. Three separate analyses were conducted, with niacin treated as a continuous, a categorical (quartiles) or a dichotomous (above/below Australian recommended daily intake) variable.In total, 4937 subjects were included in the study [Raine Study Gen2, n = 1204, median age 20; Busselton Healthy Ageing Study (BHAS), n = 1791, median age 64; TwinsUK, n = 1942, median age 64). When analysed as a continuous variable, there was no association between RNFL thickness and niacin intake in any of the three cohorts (95% CI β: Raine Study Gen 2, -0.174 to 0.074; BHAS, -0.066 to 0.078; TwinsUK -0.435 to 0.350). Similar findings were observed with quartiles of niacin intake and for niacin intakes above or below Australian recommended daily intake levels in all three cohorts.Dietary intake of niacin from a standard diet does not appear to be associated with age-related RNFL thinning in healthy eyes. Supraphysiological doses of niacin may be required for therapeutic effect in the retina.

The prevalence of reported doctor-diagnosed 'asthma' increased between 1990 and 2005-2007 in Busselton, Western Australia, accompanied by increased reported cough and phlegm but not recent wheeze. Possible reasons for the increase in diagnosed asthma include environmental exposures and diagnostic transfer. The aim of this study was to relate subject characteristics and exposures to the presence of wheeze and/or current cough/phlegm in the 2005-2007 survey.A gender- and age-stratified random sample of 2862 adults from the Busselton shire completed questionnaires regarding doctor-diagnosed asthma, respiratory symptoms and environmental exposures; and measures of anthropometry, spirometry, exhaled nitric oxide (eNO), airway hyperresponsiveness (AHR) and atopy. Associations between respiratory symptoms and subject characteristics were assessed in 2656 subjects.Wheeze was reported by 23% of subjects, cough/phlegm by 22% and both by 9%. The significant and independent correlates of wheeze were reflux symptoms, lung function, AHR, eNO, atopy, body mass index and smoking. The significant and independent correlates of cough/phlegm were reflux symptoms, lung function, smoking and dusty job. Subjects more likely to report only wheeze than only cough/phlegm were female, aged40 years, atopic, had lower percentage predicted forced expiratory volume in one second (FEV1) or higher percentage predicted force vital capacity.A variety of risk factors was associated with wheeze or cough/phlegm or both. Increased non-allergic exposures may account for increased prevalence of reported cough and phlegm and may contribute to increased reported asthma in adults.

Repetitive airway occlusion during sleep in patients with obstructive sleep apnoea (OSA) results in the generation of negative intrathoracic pressures and ends in arousal, both of which may predispose to reflux during sleep (nocturnal reflux). We aimed to determine and compare the prevalence of nocturnal reflux symptoms and their sleep-associated risk factors in untreated OSA patients, OSA patients using continuous positive airway pressure (CPAP) therapy, and the general population. Gastro-oesophageal reflux and sleep questionnaires were completed by 1116 patients with polysomnography diagnosed OSA and by 1999 participants of the 2007 Busselton population health survey. Of the OSA patients, 137 completed the reflux questionnaire before and after treatment. Risk of OSA in the general population was assessed using the Berlin score. The prevalence of frequent (weekly) nocturnal reflux symptoms was increased (P0.001) in OSA patients (10.2%) versus the general population (5.5%), in individuals from the general population at high (8.7%) versus low risk (4.3%) of OSA and in patients with severe (13.9%) versus mild OSA (5.1%). Frequent nocturnal reflux symptoms were associated with high risk (general population) (OR 1.9, P0.01) and severity of OSA (OSA population) OR 3.0, severe versus mild OSA, P0.001) after correcting for age, gender and body mass index. Treatment with CPAP decreased the prevalence of reflux symptoms significantly. In conclusion, the prevalence of nocturnal reflux symptoms is increased in those with or suspected of having OSA. This association is independent of other risk factors including age, gender and body mass index, suggesting a causal relationship between OSA and nocturnal reflux.