Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error.

Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia

Multi-trait genome-wide association study identifies new loci associated with optic disc parameters

A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH

MEASLES TRENDS AND VACCINE EFFECTIVENESS IN NAIROBI, KENYA

ABSTRACTObjectives: To determine morbidity and mortality from measles and to estimate measlesvaccine effectiveness among children hospitalised with measles in two hospitals in Nairobi.Design: A review of hospital records (index cards).Setting: Kenyatta National Hospital and Mbagathi District Hospitals covering the years1996-2000.Method: A review of index cards for measles morbility and mortality was undertaken in thetwo hospitals. Measles data at the Kenya Expanded Programme on Immunisation coveringboth hospitals was analysed for vaccine effectiveness.Results: The incidence of measles was unusually high in 1998 between July and November(monthly range 130-305), reflecting on the occurrence of an outbreak at that time. There wasno definite monthly incidence trend of measles in 1996, 1997, 1999 and 2000. The median ageof cases was 13 months (range 0-420 months) for Kenyatta hospital and 18 months (range 1-336 months) for Mbagathi Hospital. Significantly, 29.8% of all cases were aged below ninemonths when routine immunisation for measles had not begun. The median number of daysspent in hospital were five days (range 0-87 days) for Kenyatta and four days (range 1-13days) for Mbagathi. The overall case fatality rate was 5.6% and was similar for both malesand females. The overall measles vaccine effectiveness among measles cases admitted toKenyatta and Mbagathi Hospitals was 84.1%.Conclusion: The case admissions in Kenyatta and Mbagathi Hospitals suggest measles wasprevalent in Nairobi over the latter half decade of the 1990’s. Apart from 1998 when therewas an outbreak, the seasonality of measles was dampened. The 1998 outbreak suggests abuild up of susceptible children the majority of whom were born in the last quarter of 1996.The high mortality may have had to do with the majority of cases presenting late whensymptoms were already complicated and severe

Increasing prevalence of myopia in Europe and the impact of education.

PURPOSE: To investigate whether myopia is becoming more common across Europe and explore whether increasing education levels, an important environmental risk factor for myopia, might explain any temporal trend. DESIGN: Meta-analysis of population-based, cross-sectional studies from the European Eye Epidemiology (E(3)) Consortium. PARTICIPANTS: The E(3) Consortium is a collaborative network of epidemiological studies of common eye diseases in adults across Europe. Refractive data were available for 61 946 participants from 15 population-based studies performed between 1990 and 2013; participants had a range of median ages from 44 to 78 years. METHODS: Noncycloplegic refraction, year of birth, and highest educational level achieved were obtained for all participants. Myopia was defined as a mean spherical equivalent ≤-0.75 diopters. A random-effects meta-analysis of age-specific myopia prevalence was performed, with sequential analyses stratified by year of birth and highest level of educational attainment. MAIN OUTCOME MEASURES: Variation in age-specific myopia prevalence for differing years of birth and educational level. RESULTS: There was a significant cohort effect for increasing myopia prevalence across more recent birth decades; age-standardized myopia prevalence increased from 17.8% (95% confidence interval [CI], 17.6-18.1) to 23.5% (95% CI, 23.2-23.7) in those born between 1910 and 1939 compared with 1940 and 1979 (P = 0.03). Education was significantly associated with myopia; for those completing primary, secondary, and higher education, the age-standardized prevalences were 25.4% (CI, 25.0-25.8), 29.1% (CI, 28.8-29.5), and 36.6% (CI, 36.1-37.2), respectively. Although more recent birth cohorts were more educated, this did not fully explain the cohort effect. Compared with the reference risk of participants born in the 1920s with only primary education, higher education or being born in the 1960s doubled the myopia prevalence ratio-2.43 (CI, 1.26-4.17) and 2.62 (CI, 1.31-5.00), respectively-whereas individuals born in the 1960s and completing higher education had approximately 4 times the reference risk: a prevalence ratio of 3.76 (CI, 2.21-6.57). CONCLUSIONS: Myopia is becoming more common in Europe; although education levels have increased and are associated with myopia, higher education seems to be an additive rather than explanatory factor. Increasing levels of myopia carry significant clinical and economic implications, with more people at risk of the sight-threatening complications associated with high myopia

Distribution geografica de Mycosphaerella fijiensis y Mycosphaerella musicola en Costa Rica

Recherche effectuée dans 5 localités de la province de Cartago, au Costa Rica, d'octobre 1990 à février 1991, à 1350, 1000, 900 et 600 mètres d'altitud