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

Type A behaviour and prevalent heart disease in the Caerphilly study: increase in risk or symptom reporting?

Type A behaviour was assessed by modified Framingham scale in a total sample of 1956 employed men in the Caerphilly study. Prevalent heart disease was measured by cardiovascular questionnaire to obtain evidence of myocardial infarction and angina, and by electrocardiogram (ECG) for evidence of ischaemia. Type A was inversely related to age and systolic blood pressure and was positively related to social class and height. It was not related to serum cholesterol or alcohol consumption. After control for age, systolic blood pressure, height, smoking and social class, type A was found to be independent of angina but positively associated with an increased risk of possible myocardial infarction (MI). Type A was also associated with increased risk of confirmed MI. An inverse association was found between type A and asymptomatic ischaemic heart disease (IHD). The association between type A and symptomatic IHD could be due to symptom reporting

Prevalence and pattern of cognitive impairment in a community cohort of men in South Wales: methodology and findings from the Caerphilly Prospective Study.

BACKGROUND/AIMS: The prevalence of dementia and cognitive impairment not dementia was investigated in the Caerphilly Prospective Study cohort (men currently aged 65-84 years). METHODS: Of 1,633 men eligible for cognitive screening, 1,225 (75%) were seen, with those failing the screening criteria (CAMCOG 9) being neurologically examined. RESULTS: For dementia, diagnosed by DSM-IV criteria, the population prevalence was 5.2% rising to 6.1% in the screened population. For cognitive impairment not dementia, the prevalence in the screened population was 15.6% giving an overall prevalence of cognitive impairment of 21.8%. Prevalence rose fivefold between ages of 65 and 84 years to reach over 50%. CONCLUSION: These figures are likely to underestimate actual prevalence in this population, and developing effective interventions should be a public health priority