ARHGEF12 influences the risk of glaucoma by increasing intraocular pressure.

Primary open-angle glaucoma (POAG) is a blinding disease. Two important risk factors for this disease are a positive family history and elevated intraocular pressure (IOP), which is also highly heritable. Genes found to date associated with IOP and POAG are ABCA1, CAV1/CAV2, GAS7 and TMCO1. However, these genes explain only a small part of the heritability of IOP and POAG. We performed a genome-wide association study of IOP in the population-based Rotterdam Study I and Rotterdam Study II using single nucleotide polymorphisms (SNPs) imputed to 1000 Genomes. In this discovery cohort (n = 8105), we identified a new locus associated with IOP. The most significantly associated SNP was rs58073046 (ß = 0.44, P-value = 1.87 × 10(-8), minor allele frequency = 0.12), within the gene ARHGEF12. Independent replication in five population-based studies (n = 7471) resulted in an effect size in the same direction that was significantly associated (ß = 0.16, P-value = 0.04). The SNP was also significantly associated with POAG in two independent case-control studies [n = 1225 cases and n = 4117 controls; odds ratio (OR) = 1.53, P-value = 1.99 × 10(-8)], especially with high-tension glaucoma (OR = 1.66, P-value = 2.81 × 10(-9); for normal-tension glaucoma OR = 1.29, P-value = 4.23 × 10(-2)). ARHGEF12 plays an important role in the RhoA/RhoA kinase pathway, which has been implicated in IOP regulation. Furthermore, it binds to ABCA1 and links the ABCA1, CAV1/CAV2 and GAS7 pathway to Mendelian POAG genes (MYOC, OPTN, WDR36). In conclusion, this study identified a novel association between IOP and ARHGEF12.

Rationale, design and methods for the 22 year follow-up of the Western Australian Pregnancy Cohort (Raine) Study.

BACKGROUND: Young adulthood is a critical life period for health and health behaviours. Related measurements collected before and after birth, and during childhood and adolescence can provide a life-course analysis of important factors that contribute to health and behaviour in young adulthood. The Western Australian Pregnancy Cohort (Raine) Study has collected a large number of such measurements during the fetal, perinatal, infancy, childhood and adolescence periods and plans to relate them to common health issues and behaviours in young adults, including spinal pain, asthma, sleep disorders, physical activity and sedentary behaviour and, work absenteeism and presenteeism. The aim of this paper is to describe the rationale, design and methods of the 22 year follow-up of the Raine Study cohort. METHODS/DESIGN: The Raine Study is a prospective cohort study. Participants still active in the cohort (n = 2,086) were contacted around the time of their 22nd birthday and invited to participate in the 22 year follow-up. Each was asked to complete a questionnaire, attend a research facility for physical assessment and an overnight sleep study, wear activity monitors for a week, and to maintain a sleep and activity diary over this week. The questionnaire was broad and included questions related to sociodemographics, medical history, quality of life, psychological factors, lifestyle factors, spinal pain, respiratory, sleep, activity and work factors. Physical assessments included anthropometry, blood pressure, back muscle endurance, tissue sensitivity, lung function, airway reactivity, allergic status, 3D facial photographs, cognitive function, and overnight polysomnography. DISCUSSION: Describing the prevalence of these health issues and behaviours in young adulthood will enable better recognition of the issues and planning of health care resources. Providing a detailed description of the phenotype of these issues will provide valuable information to help educate health professionals of the needs of young adults. Understanding the life-course risk factors of health issues and behaviours in young adulthood will have important health planning implications, supporting the development of targeted interventions to improve current health status and reduce the onset and development of further ill-health across adulthood.

Interrogation of the platelet-derived growth factor receptor alpha locus and corneal astigmatism in Australians of Northern European ancestry: results of a genome-wide association study.

PURPOSE: Corneal astigmatism is a common eye disorder characterized by irregularities in corneal curvature. Recently, the rs7677751 single nucleotide polymorphism (SNP) at the platelet-derived growth factor receptor alpha (PDGFRA) locus was found to be associated with corneal astigmatism in people of Asian ancestry. In the present study, we sought to replicate this finding and identify other genetic markers of corneal astigmatism in an Australian population of Northern European ancestry. METHODS: Data from two cohorts were included in this study. The first cohort consisted of 1,013 individuals who were part of the Western Australian Pregnancy Cohort (Raine) Study: 20-year follow-up Eye Study. The second cohort comprised 1,788 individuals of 857 twin families who were recruited through the Twins Eye Study in Tasmania and the Brisbane Adolescent Twin Study. Corneal astigmatism was calculated as the absolute difference between the keratometry readings in two meridians, and genotype data were extracted from genome-wide arrays. Initially, each cohort was analyzed separately, before being combined for meta- and subsequent genome-wide pathway analysis. RESULTS: Following meta-analysis, SNP rs7677751 at the PDGFRA locus had a combined p=0.32. No variant was found to be statistically significantly associated with corneal astigmatism at the genome-wide level (p<5.0×10(-8)). The SNP with strongest association was rs1164064 (p=1.86×10(-6)) on chromosome 3q13. Gene-based pathway analysis identified a significant association between the Gene Ontology "segmentation" (GO:0035282) pathway, corrected p=0.009. CONCLUSIONS: Our data suggest that the PDGFRA locus does not transfer a major risk of corneal astigmatism in people of Northern European ancestry. Better-powered studies are required to validate the novel putative findings of our study.

A geometric morphometric assessment of hand shape and comparison to the 2D:4D digit ratio as a marker of sexual dimorphism.

Twin studies are extremely useful for investigating hypotheses of genetic influence on a range of behavioral and physical traits in humans. Studies of physical traits, however, are usually limited to size-related biological characteristics because it is inherently difficult to quantify the morphological counterpart - shape. In recent years, the development of geometry-preserving analytical techniques built upon multivariate statistical methodologies has produced a new discipline in biological shape analysis known as geometric morphometrics. In this study of hand shape analysis, we introduce the reader already familiar with the field of twin research to the potential utility of geometric morphometrics and demonstrate the cross-discipline applicability of methods. We also investigate and compare the efficacy of the 2D:4D ratio, a commonly used marker of sexual dimorphism, to the fully multivariate approach of shape analysis in discriminating between male and female sex. Studies of biological shape variation utilizing geometric morphometric techniques may be completed with software freely available on the Internet and time invested to master the small learning curve in concepts and theory.

Influence of prenatal environment and birth parameters on amblyopia, strabismus, and anisometropia.

PURPOSE: To report the prevalence of amblyopia, strabismus, and anisometropia in a young adult population at a single center in Australia and to investigate the underlying prenatal and early-life risk factors. METHODS: Participants in the Raine Study have been followed from mid-gestation (n = 2,868 newborns) to young adulthood. At age 20 years, 1,344 participants had a comprehensive eye examination, including visual acuity and a detailed orthoptic assessment. Risk factors were determined from medical records and questionnaires completed by the mothers at 18 weeks' gestation. The main outcome measures were the proportions of participants with amblyopia, esotropia, exotropia, or anisometropia (defined as >1 D difference). RESULTS: Of the 1,125 white participants, 12 (1.1%) had amblyopia, 39 (3.5%) had strabismus, and 33 (2.9%) had anisometropia. In multivariable logistic regression, amblyopia was associated with a maternal history of pregnancy-induced hypertension (OR = 3.80; 95% CI, 1.19-12.13); esotropia, with lower gestational age (OR = 0.97; 95% CI, 0.95-0.97) and a heavier placenta (OR = 1.02; 95% CI, 1.00-1.04); exotropia, with a maternal history of previously treated hypertension (OR = 4.00; 95% CI, 1.06-15.03) and maternal use of recreational drugs during early pregnancy (OR = 3.61; 95% CI, 1.06-15.03); and anisometropia, with older maternal age (OR = 1.07; 95% CI, 1.01-1.14) and an abnormal umbilical cord (OR = 2.39; 95% CI, 1.04-5.47). CONCLUSIONS: The prevalence of amblyopia, strabismus, and anisometropia in this cohort was similar to that in other studies. Preterm birth and maternal health may have adverse effects on eye development.

Tracking of vitamin D status from childhood to early adulthood and its association with peak bone mass.

Background: To our knowledge, there are few longitudinal studies of vitamin D status from childhood to early adulthood, and it is uncertain whether vitamin D predicts peak bone mass in young adults.Objectives: The purpose of this longitudinal study was to evaluate the long-term stability of vitamin D status from ages 6 to 20 y in healthy individuals and to study associations between serum 25-hydroxyvitamin D [25(OH)D] at different developmental stages and bone mass measured at age 20 y.Design: Participants were offspring of the Western Australian Pregnancy Cohort (Raine) study. Serum 25(OH)D was assessed at ages 6, 14, 17, and 20 y, and whole-body bone mineral content (BMC) and bone mineral density (BMD) were measured at age 20 y through the use of dual-energy X-ray absorptiometry (DXA). Our analysis included 821 participants (385 females) who had ≥3 serum 25(OH)D measures and DXA data. We used latent class growth analysis and identified 4 vitamin D status trajectories: consistently lower (n = 259), decreasing (n = 125), increasing (n = 138), and consistently higher (n = 299).Results: There were significant correlations between serum 25(OH)D concentrations at different time points in both sexes (r = 0.346-0.560, P < 0.001), with stronger correlations at adjacent time points. In males, but not in females, serum 25(OH)D at ages 6, 17, and 20 y was positively associated with total-body BMC and BMD at age 20 y [covariate-adjusted increments of 40.7-53.9 g and 14.7-18.6 mg/cm2, respectively, per 25 nmol/L 25(OH)D]; when 25(OH)D at all 4 ages was included in the same model, the concentration at age 6 y remained significant. Males in the "consistently higher" trajectory had 3.2-3.4% higher total body BMC and BMD than those who were in the "consistently lower" trajectory, accounting for age and anthropometric and lifestyle factors.Conclusions: Within both sexes, there are moderate associations between vitamin D status measured in prepuberty, adolescence, and early adulthood. Vitamin D status in childhood is a significant predictor of peak bone mass in male but not female subjects.

Providers and consumers support the Western Australian Audit of Surgical Mortality.

BACKGROUND: The Western Australian Audit of Surgical Mortality (WAASM) was established in June 2001 to independently peer-review all surgical deaths in Western Australia. The objectives of this study were (i) to evaluate whether participation in the WAASM has influenced clinical and hospital practice; and (ii) to ascertain the support and relevance of the WAASM to surgeons, hospitals and consumers. METHODS: Three qualitative questionnaires were designed to evaluate the response of surgeons, hospital administrators and consumers to the WAASM. The outcomes measured included audit participation, value and use of feedback provided, changes to clinical and hospital practice and the future role of the WAASM. RESULTS: The key findings were that 138 (73%) of 190 surgeons participating in the WAASM had changed their clinical practice in at least one way, 44 (24%) were aware of changes in hospital practice and 21 (11%) were aware of changes in a colleague's practice. Particular areas where changes in surgical practice had occurred included attention to deep vein thrombosis prophylaxis (81, 44%), increased constructive discussion among peers (78, 42%) and quality of documentation in case notes (68, 37%). All groups supported the continuation of the WAASM. Hospital executives and consumers recommended that the WAASM be included in accreditation. CONCLUSION: Surgeons, hospitals and consumers supported the concept of independent peer review of surgical care. They confirmed the ability of audit to influence and change surgical and hospital practice. It strengthens the intention of the Royal Australasian College of Surgeons to extend the WAASM project throughout Australia and New Zealand.

Associations between hypothalamic-pituitary-adrenal axis function and peak bone mass at 20years of age in a birth cohort.

In older adults, high-normal circulating cortisol levels are associated with lower bone mass, but relationships between hypothalamic-pituitary-adrenal axis function and peak bone mass in young adults have not been examined. We studied 411 male and 390 female participants in the Western Australia Pregnancy Cohort (Raine) Study. At 18years of age, participants underwent a Trier Social Stress Test (TSST) with measurement of plasma and salivary cortisol at baseline and at multiple time points after stress. Cortisol responses were classified as anticipatory responder (significant fall in cortisol during the test), reactive responder (significant increase) or non-responder. At 20years, total body bone mineral content (BMC) and density (BMD) were measured by DXA. In males, after adjustment for weight, height (for BMC and bone area only), alcohol and smoking, there was a significant inverse relationship between both plasma and salivary cortisol measured at baseline in the TSST and each of BMC and BMD, such that each additional 10% of salivary cortisol was associated with reductions of 6.9g (95% CI -11.7, -2.2) in BMC, and 1.8mg/cm(2) (95% CI -3.3, -0.4) in BMD. Males classified as anticipatory responders in the TSST had 3.2% lower BMC (adjusted mean±SE: 3131±28 vs. 3233±18g, P=0.006) and 2.5% lower BMD (1108±9 vs. 1136±6mg/cm(2), P=0.022) than reactive responders. In females, there were no significant relationships between baseline cortisol or TSST responses and BMC or BMD in covariate-adjusted analyses. We conclude that in young males (but not females), higher circulating cortisol at the baseline of the stress test and an anticipatory responder pattern on the TSST are associated with lower total body bone mass.

Data linkage in an established longitudinal cohort: the Western Australian Pregnancy Cohort (Raine) Study.

The Western Australian Data Linkage System is one of a few comprehensive, population-based data linkage systems worldwide, creating links between information from different sources relating to the same individual, family, place or event, while maintaining privacy. The Raine Study is an established cohort study with more than 2000 currently active participants. Individual consent was obtained from participants for information in publicly held databases to be linked to their study data. A waiver of consent was granted where it was impracticable to obtain consent. Approvals to link the datasets were obtained from relevant ethics committees and data custodians. The Raine Study dataset was subsequently linked to academic testing data collected by the Western Australian Department of Education. Examination of diet and academic performance showed that children who were predominantly breastfed for at least 6 months scored higher academically at age 10 than children who were breastfed for less than 6 months. A further study found that better diet quality at ages 1, 2 and 3 years was associated with higher academic scores at ages 10 and 12 years. Examination of nutritional intake at 14 years of age found that a better dietary pattern was associated with higher academic performance. The detailed longitudinal data collected in the Raine Study allowed for adjustment for multiple covariates and confounders. Data linkage reduces the burden on cohort participants by providing additional information without the need to contact participants. It can give information on participants who have been lost to follow-up; provide or complement missing data; give the opportunity for validation studies comparing recall of participants with administrative records; increase the population sample of studies by adding control participants from the general population; and allow for the adjustment of multiple covariates and confounders. The Raine Study dataset is extensive and detailed, and can be further improved by linking to other external data sources. By linking educational outcomes to the Raine Study database, it was shown across three different age groups that a healthy diet was consistently associated with higher academic performance.

Longitudinal Trajectories of Television Watching Across Childhood and Adolescence Predict Bone Mass at Age 20 Years in the Raine Study.

Sedentary behaviors such as watching television (TV) are associated with increased risk of cardiometabolic disease. The effects of TV watching during key developmental stages on skeletal health are uncertain. Hours of TV watching/week were recorded by parental or self-report at 5, 8, 10, 14, 17, and 20 years of age in 1181 members (48% female) of a pregnancy cohort (the Raine Study). Participants were classified into one of three TV-watching trajectories (using latent class analysis): low (consistently <14 h/week; 20.3%), high (consistently ≥14 h/week; 44.4%), or increasing (increased from <14 to ≥14 h/week during adolescence; 35.3%). General linear models tested associations between TV trajectory and bone mineral content (BMC) measured at age 20 years using dual-energy X-ray absorptiometry. After adjustment for height, body mass, physical activity, calcium intake, serum 25-hydroxyvitamin D levels, alcohol, and smoking (all at age 20 years), males in the low TV-watching trajectory had greater BMC for whole body (mean ± SEM, 3338 ± 59 g versus 3111 ± 31 g), legs (612 ± 12 g versus 569 ± 6 g), and arms (234 ± 5 g versus 214 ± 3 g) than those in the high TV-watching trajectory. Differences between low and high TV-watching trajectories were similar for females. BMC in the increasing TV-watching trajectory also differed for both sexes, for example males in the increasing TV-watching trajectory had greater whole-body BMC (3252 ± 38 g) than males in the high TV-watching trajectory (3111 ± 31 g) but less arm BMC (218 ± 3 g) than those in the low TV-watching trajectory (234 ± 5 g). In this community-based cohort, consistently high TV watching during childhood and adolescence independently predicted reduced peak bone mass at age 20 years. Because attainment of optimal peak bone mass is protective against osteoporosis in later life, reducing sedentary time in children may have long-term skeletal benefits. © 2016 American Society for Bone and Mineral Research.

Identification of a dietary pattern prospectively associated with bone mass in Australian young adults.

BACKGROUND: Relatively little is known about the relations between dietary patterns and bone health in adolescence, which is a period of substantial bone mass accrual. OBJECTIVES: We derived dietary patterns that were hypothesized to be related to bone health on the basis of their protein, calcium, and potassium contents and investigated their prospective associations with bone mineral density (BMD), bone area, and bone mineral content (BMC) in a cohort of young adults. DESIGN: The study included 1024 young adults born to mothers who were participating in the Western Australian Pregnancy Cohort (Raine) Study. Dietary information was obtained from food-frequency questionnaires at 14 and 17 y of age. Dietary patterns were characterized according to protein, calcium, and potassium intakes with the use of reduced-rank regression. BMD, bone area, and BMC were estimated with the use of a total body dual-energy X-ray absorptiometry scan at 20 y of age. RESULTS: We identified 2 major dietary patterns. The first pattern was positively correlated with intakes of protein, calcium, and potassium and had high factor loadings for low-fat dairy products, whole grains, and vegetables. The second pattern was positively correlated with protein intake but negatively correlated with intakes of calcium and potassium and had high factor loadings for meat, poultry, fish, and eggs. After adjustment for anthropometric, sociodemographic, and lifestyle factors, a higher z score for the first pattern at 14 y of age was positively associated with BMD and BMC at 20 y of age [differences: 8.6 mg/cm(2) (95% CI: 3.0, 14.1 mg/cm(2)) and 21.9 g (95% CI: 6.5, 37.3 g), respectively, per SD increase in z score]. The z score for this same pattern at 17 y of age was not associated with bone outcomes at 20 y of age. The second pattern at 14 or 17 y of age was not associated with BMD, BMC, or bone area. CONCLUSIONS: A dietary pattern characterized by high intakes of protein, calcium, and potassium in midadolescence was associated with higher BMD and BMC at 20 y of age. Our results indicate that high consumption of low-fat dairy products, whole grains, and vegetables in adolescence are associated with beneficial effects on bone development.

Heightened cold pain and pressure pain sensitivity in young female adults with moderate-to-severe menstrual pain.

This study investigated the association between menstrual pain severity and psychophysical measures of cold and pressure pain sensitivity. A cross-sectional design was used with young women (n = 432) from the Western Australian Pregnancy Cohort (Raine) Study. Menstrual pain severity and oral contraception use was obtained from questionnaires at 20 and 22-year follow-ups. A visual analog scale (VAS; range from 0 [none] to 10 [unbearable]) was used to measure menstrual pain severity at both 20 and 22 years over the 3-year period, with 3 groups created: (1) no pain or mild pain (VAS 0-3), (2) at least moderate pain at a minimum of 1 of the 2 time points (hereafter named "mixed)", and (3) severe pain (VAS 8-10). Cold pain sensitivity (dorsal wrist) and pressure pain sensitivity (lumbar spine, upper trapezius, dorsal wrist, and tibialis anterior) were assessed using standardised quantitative sensory testing protocols. Confounding variables included number of musculoskeletal pain sites, oral contraceptive use, smoking, physical activity, body mass index, psychological distress, and sleep. Severe menstrual pain and mixed menstrual pain were positively associated with heightened cold pain sensitivity (distant from menstrual pain referral site) and pressure pain sensitivity (local to menstrual pain referral site). These associations remained significant after adjusting for potential confounding variables including multisite musculoskeletal pain. Our findings suggest peripheral and central neurophysiological mechanisms contributing to heightened pain sensitivity in young women with moderate and severe menstrual pain. These data highlight the need for innovative management approaches to attenuate the negative impact of severe menstrual pain in young women.

Vitamin D in fetal development: findings from a birth cohort study.

Birth cohort studies provide an invaluable resource for studies of the influence of the fetal environment on health in later life. It is uncertain to what extent maternal vitamin D status influences fetal development. Using an unselected community-based cohort of 901 mother-offspring pairs (the Western Australian Pregnancy Cohort [Raine] Study), we examined the relationship between maternal vitamin D deficiency at 18 weeks' pregnancy and long-term health outcomes of offspring who were born in Perth, Western Australia (32° South), in 1989-1991. Vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] <50 nmol/L) was present in 36% (323 of 901) of the pregnant women. After adjusting for relevant covariates, maternal vitamin D deficiency during pregnancy was associated with impaired lung development in 6-year-old offspring, neurocognitive difficulties at age 10, increased risk of eating disorders in adolescence, and lower peak bone mass at 20 years. In summary, vitamin D may have an important, multifaceted role in the development of fetal lungs, brain, and bone. Experimental animal studies support an active contribution of vitamin D to organ development. Randomized controlled trials of vitamin D supplementation in pregnant women with long-term follow-up of offspring are urgently required to examine whether the correction of vitamin D deficiency in pregnant women is beneficial for their offspring and to determine the optimal level of maternal serum 25(OH)D for fetal development.

Genetic and environmental factors in conjunctival UV autofluorescence.

IMPORTANCE: Conjunctival UV autofluorescence (CUVAF) photography was developed to detect and characterize preclinical sunlight-induced ocular damage. Ocular sun exposure has been related to cases of pterygia and was recently negatively correlated with myopia. Hence, CUVAF has excellent potential as an objective biomarker of sun exposure. However, much variation in CUVAF has been observed, and the relative contributions of genes and environment to this variation have not yet been identified. OBJECTIVE: To investigate sources of variation in CUVAF in relation to its potential clinical relevance. DESIGN, SETTING, AND PARTICIPANTS: We performed a cross-sectional analysis of 3 population-based cohort studies in the general community, including the Twins Eye Study in Tasmania, the Brisbane Adolescent Twin Study, and the Western Australian Pregnancy Cohort (Raine) Study. The twin studies were conducted between 2001 and 2009, and the 20-year follow-up of the Raine Study was completed between March 2010 and February 2012. We included genotypic and phenotypic data from 295 Australian families in the Tasmanian and Brisbane twin studies and from 661 participants in the 20-year follow-up of the Raine Study. We compared CUVAF levels in the 3 cohorts and performed a classic twin study to partition variation in CUVAF. We also conducted a genome-wide association analysis to identify specific genetic variants associated with CUVAF. MAIN OUTCOMES AND MEASURES: The total area of CUVAF, heritability of CUVAF, and single-nucleotide polymorphisms (SNPs) associated with CUVAF from the genome-wide association study. RESULTS: Within twin cohorts, individuals living closer to the equator (latitude, 27.47° S) had higher levels of CUVAF compared with individuals from southern regions (latitude, 42.88° S) (median [interquartile range], 45.4 [26.8-68.5] vs 28.7 [15.0-42.3] mm2; P < .001). The variation in CUVAF explained by the additive genetic component was 0.37 (95% CI, 0.22-0.56), whereas the variation due to the common environment was 0.50 (95% CI; 0.29-0.71). The SNP rs1060043, located approximately 800 base pairs away from the SLC1A5 gene, a member of the solute carrier family 1, had a genome-wide significant association with a P value of 3.2 × 10-8. Gene-based analysis did not improve our power to detect association with other genes. CONCLUSIONS AND RELEVANCE: Our findings confirm that, although a large environmental component to CUVAF (equivalent of sun exposure) exists, genes also play a significant role. We identified a SNP (rs1060043) as being significantly associated with CUVAF; replication of this finding in future studies is warranted.

Maternal vitamin D status during pregnancy and bone mass in offspring at 20 years of age: a prospective cohort study.

It is uncertain whether the vitamin D status of pregnant women influences bone mass of their children. Cohort studies have yielded conflicting results; none have examined offspring at skeletal maturity. This longitudinal, prospective study investigated the association between maternal vitamin D status and peak bone mass of offspring in 341 mother and offspring pairs in the Western Australian Pregnancy Cohort (Raine) Study. Maternal serum samples collected at 18 weeks gestation were assayed for 25-hydroxyvitamin D (25OHD). Outcomes were total body bone mineral content (BMC) and bone mineral density (BMD) measured by dual-energy X-ray absorptiometry in offspring at 20 years of age. The mean (± SD) maternal serum 25OHD concentration was 57.2 ± 19.2 nmol/L; 132 women (38.7%) were vitamin D-deficient (25OHD <50 nmol/L). After adjustment for season of sample collection, maternal factors, and offspring factors (sex, birth weight, and age, height, lean mass, and fat mass at 20 years), maternal 25OHD concentration was positively associated with total body BMC and BMD in offspring, with a mean difference of 19.2 (95% confidence interval [CI], 5.6-32.7) g for BMC and 4.6 (95% CI, 0.1-9.1) mg/cm(2) for BMD per 10.0 nmol/L of maternal 25OHD. Maternal vitamin D deficiency was associated with 2.7% lower total body BMC (mean ± SE) (2846 ± 20 versus 2924 ± 16 g, p = 0.004) and 1.7% lower total body BMD (1053 ± 7 versus 1071 ± 5 mg/cm(2) , p = 0.043) in the offspring. We conclude that vitamin D deficiency in pregnant women is associated with lower peak bone mass in their children. This may increase fracture risk in the offspring in later life.

Comparison of monochromatic aberrations in young adults with different visual acuity and refractive errors.

PURPOSE: To compare the monochromatic aberrations in a large cohort of 20-year-old Australians with differing levels of visual acuity and explore the relationship between these aberrations and refractive error. SETTING: Lions Eye Institute, Perth, Western Australia, Australia. DESIGN: Cross-sectional analysis of a population-based cohort. METHODS: Monochromatic aberrations were measured using a Zywave II wavefront aberrometer with natural pupils in a dark room. The logMAR corrected distance visual acuity (CDVA) was measured monocularly under normal illumination. Cycloplegic autorefraction was also performed. RESULTS: The study enrolled 2039 eyes of 1040 participants. Data from 1007 right eyes were analyzed. The median CDVA and spherical equivalent were -0.06 logMAR (interquartile range [IQR], -0.10 to 0.00) and +0.25 diopters (D) (IQR, -0.38 to 0.63), respectively. The median 6.0 mm higher-order aberration (HOA) was 0.58 µm (IQR, 0.44 to 0.79). Coma-like aberrations and 3rd-, 4th-, and 5th-order HOAs were significantly different between subjects with a CDVA of -0.10 logMAR or better and those with a CDVA worse than -0.10 logMAR. Fourth-order aberrations Z(4,-4) (P=.024) and Z(4,-2) (P=.029) and 2nd-order aberration Z(2,0) (P<.001) differed significantly between myopic eyes, emmetropic eyes, and hyperopic eyes. Subjects with higher myopia had slightly higher total HOAs. CONCLUSIONS: The HOAs in this population were marginally higher than previously reported values. The findings confirm there is a difference in monochromatic aberrations between different vision and refractive groups. Results in this study will benefit decision-making processes in the clinical setting.

Myopia is associated with lower vitamin D status in young adults.

PURPOSE: To investigate the association between serum vitamin D levels and myopia in young adults. METHODS: A total of 946 individuals participating in the 20-year follow-up of the Western Australian Pregnancy Cohort (Raine) Study were included in this study. Ethnicity, parental myopia, and education status were ascertained by self-reported questionnaire. A comprehensive ophthalmic examination was performed, including postcycloplegic autorefraction and conjunctival UV autofluorescence photography. Serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations were determined using mass spectrometry. The association between serum 25(OH)D3 concentrations and prevalent myopia was determined using multivariable logistic regression. Myopia was defined as mean spherical equivalent ≤ -0.5 diopters. RESULTS: Of the 946 participants, 221 (23.4%) had myopia (n = 725 nonmyopic). Myopic subjects had lower serum 25(OH)D3 concentrations compared to nonmyopic participants (median 67.6 vs. 72.5 nmol, P = 0.003). In univariable analysis, lower serum 25(OH)D3 concentration was associated with higher risk of having myopia (odds ratio [OR] for <50 vs. ≥50 nmol/L: 2.63; confidence interval [95% CI] 1.71-4.05; P < 0.001). This association persisted after adjustment for potential confounders, including age, sex, ethnicity, parental myopia, education status, and ocular sun-exposure biomarker score (adjusted OR 2.07; 95% CI 1.29-3.32; P = 0.002). CONCLUSIONS: Myopic participants had significantly lower 25(OH)D3 concentrations. The prevalence of myopia was significantly higher in individuals with vitamin D deficiency compared to the individuals with sufficient levels. Longitudinal studies are warranted to investigate whether higher serum 25(OH)D3 concentration is protective against myopia or whether it is acting as a proxy for some other biologically effective consequence of sun exposure.

Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process.

Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindness worldwide. Here, the International Glaucoma Genetics Consortium conducts a meta-analysis of genome-wide association studies of vertical cup-disc ratio (VCDR), an important disease-related optic nerve parameter. In 21,094 individuals of European ancestry and 6,784 individuals of Asian ancestry, we identify 10 new loci associated with variation in VCDR. In a separate risk-score analysis of five case-control studies, Caucasians in the highest quintile have a 2.5-fold increased risk of primary open-angle glaucoma as compared with those in the lowest quintile. This study has more than doubled the known loci associated with optic disc cupping and will allow greater understanding of mechanisms involved in this common blinding condition.