A proteogenomic signature of age-related macular degeneration in blood

© 2022. The Author(s). Funding Information: The authors acknowledge the contribution of the Icelandic Heart Association (IHA) staff to the AGES-RS, as well as the involvement of all study participants. We thank the IAMDGC consortium for supplying us with their GWAS summary statistics data. National Institute on Aging (NIA) contracts N01-AG-12100 and HHSN271201200022C for V.G. financed the AGES study; retinal image collection and AMD readings were funded by the NIH Intramural Research Program (ZIAEY000401). V.G. received a funding from the NIA (1R01AG065596), and IHA received a support from Althingi (the Icelandic Parliament). The Icelandic Research Fund (IRF) funded V.E. and Va.G. with grants 195761-051, 184845-053, and 206692-051, while Va.G. received a postdoctoral research grant from the University of Iceland Research Fund Funding Information: The study was supported by the Novartis Institute for Biomedical Research. M.T., N.F., S.P., X.L., R.E., Y.Z., S.J., C.L.H., S.M.L., J.L., C.L.G., A.A.N., B.L., R.P., Z.L., L.L.J., T.E.W., Q.Z., Q.H., and J.R.L. are employees and stockholders of Novartis. All other authors have no conflict of interests to declare. Publisher Copyright: © 2022, The Author(s).Age-related macular degeneration (AMD) is one of the most common causes of visual impairment in the elderly, with a complex and still poorly understood etiology. Whole-genome association studies have discovered 34 genomic regions associated with AMD. However, the genes and cognate proteins that mediate the risk, are largely unknown. In the current study, we integrate levels of 4782 human serum proteins with all genetic risk loci for AMD in a large population-based study of the elderly, revealing many proteins and pathways linked to the disease. Serum proteins are also found to reflect AMD severity independent of genetics and predict progression from early to advanced AMD after five years in this population. A two-sample Mendelian randomization study identifies several proteins that are causally related to the disease and are directionally consistent with the observational estimates. In this work, we present a robust and unique framework for elucidating the pathobiology of AMD.Peer reviewe

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

Pseudoexfoliation in the Reykjavik Eye Study: prevalence and related ophthalmological variables.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldPURPOSE: To examine the age and sex-specific prevalence of pseudoexfoliation syndrome (PEX) and its relationship with some ophthalmological variables. METHODS: We carried out a population-based study using a random sample taken from the national population census for citizens of Reykjavik, aged > or = 50 years. A total of 1045 individuals participated in all parts of the study. Pseudoexfoliation was established by slit-lamp examination with a maximally dilated pupil carried out by two experienced ophthalmologists, who were masked to one another's results except in cases of disagreement where they had to reach a consensus. RESULTS: In all, 108 (10.7%) persons were found to have PEX in at least one eye. Prevalence increased from 2.5% in those aged 50-59 years to 40.6% in those aged > or = 80 years. Women were more frequently affected than men (12.3% versus 8.7%). This difference remained statistically significant after controlling for the effect of age (p < 0.001). Eyes with PEX were found to have higher intraocular pressure (IOP) than eyes without PEX (p < 0.05). However, PEX was not found to be related to central corneal thickness, anterior chamber depth, lens thickness, nuclear lens opacifications or optic disc morphology in a multivariate model. CONCLUSIONS: Pseudoexfoliation is an age-related phenomenon commonly found in Iceland. It is more commonly found in women than in men and is associated with elevated IOP

Alaska military expedition in charge of Captain W. R. Abercrombie, U.S.A. Prince William Sound and vicinity 1898 [cartographic material] /

Map of the Prince William Sound region in Alaska with relief shown by contours.; In upper right-hand corner: Report, Public Resolution No. 25, 55th Congress, 3D Session.; "Map 8."; In upper left-hand corner: U.S. Geological Survey Charles D. Walcott, Director.; Also available in an electronic version via the Internet at: http://nla.gov.au/nla.map-rm1538

Exfoliation syndrome in the Reykjavik eye study: Risk factors for baseline prevalence and 5-year incidence

Aim: To examine the age- and gender-specific prevalent and 5-year incident risk of developing exfoliation syndrome (XFS).Methods and participants: In a population-based random sample of citizens 50 years and older, 1045 persons had baseline examination in 1996; 846 of the 958 survivors (88.2%) had a follow-up examination in 2001. Following maximum dilatation of pupils, a diagnosis of exfoliation was established on slit-lamp examination. An extensive questionnaire was administered at baseline and follow-up. Prevalent and incident risk was then calculated using a multivariate analysis.Results: The following variables were found to correlate significantly with prevalence risk of XFS at baseline: age, female gender, increased iris pigmentation, moderate use of alcohol and self-reported asthma. We also found that, compared with those who consumed dietary fibre-rich vegetables, green or yellow vegetables, and fruit less than once a month in their 20s and 40s, those consuming the same food items once or twice every 2 weeks were found to be less likely to have XFS. The same applied to those consuming dietary fibre rich once or twice every 2 weeks in their 40s and 60s.Conclusion: Food items that are possibly surrogates for antioxidative effect may correlate with decreased risk of XFS and increased iris pigmentation may correlate with increased risk. Given the large number of comparisons, these findings require validation through additional clinical studies. Increased age and female gender increase the likelihood of XFS

Macular corneal dystrophy types I and II are caused by distinct mutations in the CHST6 gene in Iceland.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldPURPOSE: To identify CHST6 mutations in five additional Icelandic cases of macular corneal dystrophy (MCD) type I and in four families with MCD type II from Iceland. METHODS: Genomic DNA was extracted from blood leukocytes of patients with MCD, their healthy family members, and from control individuals. CHST6 mutations were determined by PCR-sequencing. Immunophenotypes of MCD were determined by measuring antigenic keratan sulfate (AgKS) levels in serum and by an immunohistochemical study on corneal tissue. RESULTS: Five additional cases of MCD type I and four families with MCD type II from Iceland were studied. A homozygous p.A128V mutation in the coding region of the CHST6 gene was identified in four of the five MCD type I cases. The other person with MCD type I was a compound heterozygote for p.A128V and a frameshift p.V6fs resulting from a 10-base pair insertion (c.15_16insATGCTGTGCG). Four of five individuals with MCD type II were compound heterozygotes for p.A128V and p.V329L, thus sharing the same p.A128V mutation as MCD type I. One patient with MCD type II was homozygous for p.V329L. The p.V329L mutation was only found in MCD type II patients. An analysis of the upstream region of CHST6 disclosed no upstream deletion or replacements in Icelandic patients with MCD type II. CONCLUSIONS: The findings fit the haplotype analysis that we reported previously in Icelandic MCD families and indicate that different mutations in CHST6 cause MCD type I and type II in Iceland