Explore the vast range of titles available.

Intraocular pressure (IOP) is currently the sole modifiable risk factor for primary open-angle glaucoma (POAG), one of the leading causes of blindness worldwide 1 . Both IOP and POAG are highly heritable 2 . We report a combined analysis of participants from the UK Biobank ( n  = 103,914) and previously published data from the International Glaucoma Genetic Consortium ( n  = 29,578) 3 , 4 that identified 101 statistically independent genome-wide-significant SNPs for IOP, 85 of which have not been previously reported 4 – 12 . We examined these SNPs in 11,018 glaucoma cases and 126,069 controls, and 53 SNPs showed evidence of association. Gene-based tests implicated an additional 22 independent genes associated with IOP. We derived an allele score based on the IOP loci and loci influencing optic nerve head morphology. In 1,734 people with advanced glaucoma and 2,938 controls, participants in the top decile of the allele score were at increased risk (odds ratio (OR) = 5.6; 95% confidence interval (CI): 4.1–7.6) of glaucoma relative to the bottom decile. A combined analysis of participants from the UK Biobank and the International Glaucoma Genetic Consortium identifies 85 new loci for intraocular pressure (IOP). Pathway analysis uncovers new pathways associated with both IOP and glaucoma.

Jamie Craig, Puya Gharahkhani and colleagues report results of a genome-wide association study of primary open-angle glaucoma. They identify common variants near ABCA1, AFAP1 and GMDS that are associated with risk of this disease. Primary open-angle glaucoma (POAG) is a major cause of irreversible blindness worldwide. We performed a genome-wide association study in an Australian discovery cohort comprising 1,155 cases with advanced POAG and 1,992 controls. We investigated the association of the top SNPs from the discovery stage in two Australian replication cohorts (932 cases and 6,862 controls total) and two US replication cohorts (2,616 cases and 2,634 controls total). Meta-analysis of all cohorts identified three loci newly associated with development of POAG. These loci are located upstream of ABCA1 (rs2472493[G], odds ratio (OR) = 1.31, P = 2.1 × 10 −19 ), within AFAP1 (rs4619890[G], OR = 1.20, P = 7.0 × 10 −10 ) and within GMDS (rs11969985[G], OR = 1.31, P = 7.7 × 10 −10 ). Using RT-PCR and immunolabeling, we show that these genes are expressed within human retina, optic nerve and trabecular meshwork and that ABCA1 and AFAP1 are also expressed in retinal ganglion cells.

Open-angle glaucoma (OAG) is a major cause of blindness worldwide. To identify new risk loci for OAG, we performed a genome-wide association study in 3,071 OAG cases and 6,750 unscreened controls, and meta-analysed the results with GWAS data for intraocular pressure (IOP) and optic disc parameters (the overall meta-analysis sample size varying between 32,000 to 48,000 participants), which are glaucoma-related traits. We identified and independently validated four novel genome-wide significant associations within or near MYOF and CYP26A1 , LINC02052 and CRYGS , LMX1B , and LMO7 using single variant tests, one additional locus ( C9 ) using gene-based tests, and two genetic pathways - “response to fluid shear stress” and “abnormal retina morphology” - in pathway-based tests. Interestingly, some of the new risk loci contribute to risk of other genetically-correlated eye diseases including myopia and age-related macular degeneration. To our knowledge, this study is the first integrative study to combine genetic data from OAG and its correlated traits to identify new risk variants and genetic pathways, highlighting the future potential of combining genetic data from genetically-correlated eye traits for the purpose of gene discovery and mapping.

Epidemiologic studies have reported inconsistent results regarding an association between Parkinson disease (PD) and cutaneous melanoma (melanoma). Identifying shared genetic architecture between these diseases can support epidemiologic findings and identify common risk genes and biological pathways. Here, we apply polygenic, linkage disequilibrium-informed methods to the largest available case–control, genome-wide association study summary statistic data for melanoma and PD. We identify positive and significant genetic correlation (correlation: 0.17, 95% CI 0.10–0.24; P  = 4.09 × 10 −06 ) between melanoma and PD. We further demonstrate melanoma and PD-inferred gene expression to overlap across tissues (correlation: 0.14, 95% CI 0.06 to 0.22; P  = 7.87 × 10 −04 ) and highlight seven genes including PIEZO1 , TRAPPC2L , and SOX6 as potential mediators of the genetic correlation between melanoma and PD. These findings demonstrate specific, shared genetic architecture between PD and melanoma that manifests at the level of gene expression.

The original version of this article unfortunately contained a mistake. Supplementary Tables 3 and 4 are not available with the rest of the supplementary material available online.The original version of this article unfortunately contained a mistake. Supplementary Tables 3 and 4 are not available with the rest of the supplementary material available online.

This benchmark volume documents in comprehensive detail a major environmental crisis: rapidly declining amphibian populations and the disturbing developmental problems that are increasingly prevalent within many amphibian species. Horror stories on this topic have been featured in the scientific and popular press over the past fifteen years, invariably asking what amphibian declines are telling us about the state of the environment. Are declines harbingers of devastated ecosystems or simply weird reflections of a peculiar amphibian world? This compendium—presenting new data, reviews of current literature, and comprehensive species accounts—reinforces what scientists have begun to suspect, that amphibians are a lens through which the state of the environment can be viewed more clearly. And, that the view is alarming and presages serious concerns for all life, including that of our own species. The first part of this work consists of more than fifty essays covering topics from the causes of declines to conservation, surveys and monitoring, and education. The second part consists of species accounts describing the life history and natural history of every known amphibian species in the United States.

A series of water vapor intensive observation periods (WVIOPs) were conducted at the Atmospheric Radiation Measurement (ARM) site in Oklahoma between 1996 and 2000. The goals of these WVIOPs are to characterize the accuracy of the operational water vapor observations and to develop techniques to improve the accuracy of these measurements. The initial focus of these experiments was on the lower atmosphere, for which the goal is an absolute accuracy of better than 2% in total column water vapor, corresponding to ∼1 W m−2of infrared radiation at the surface. To complement the operational water vapor instruments during the WVIOPs, additional instrumentation including a scanning Ramanlidar, microwave radiometers, chilled-mirror hygrometers, a differential absorption lidar, and ground-based solar radiometers were deployed at the ARM site. The unique datasets from the 1996, 1997, and 1999 experiments have led to many results, including the discovery and characterization of a large (> 25%) sonde-to-sonde variability in the water vapor profiles from Vaisala RS-80H radiosondes that acts like a height-independent calibration factor error. However, the microwave observations provide a stable reference that can be used to remove a large part of the sonde-to-sondecalibration variability. In situ capacitive water vapor sensors demonstrated agreement within 2% of chilled-mirror hygrometers at the surface and on an instrumented tower. Water vapor profiles retrieved from two Raman lidars,which have both been calibrated to the ARM microwave radiometer, showed agreement to within 5% for all altitudes below 8km during two WVIOPs. The mean agreement of the total precipitable water vapor from different techniques has converged significantly from early analysis that originally showed differences up to 15%. Retrievals of total precipitablewater vapor (PWV) from the ARM microwave radiometer are now found to be only 3% moister than PWV derived from new GPSresults, and about 2% drier than the mean of radiosonde data after a recently defined sonde dry-bias correction is applied. Raman lidar profiles calibrated using tower-mounted chilled-mirror hygrometers confirm the expected sensitivityof microwave radiometer data to water vapor changes, but is drier than the microwave radiometer (MWR) by 0.95 mm for all PWV amounts. However, observations from different collocated microwave radiometers have shown larger differences than expected and attempts to resolve the remaining inconsistencies (in both calibration andforward modeling) are continuing. The paper concludes by outlining the objectives of the recent 2000 WVIOP and the ARM-First International Satellite Cloud Climatology Project (ISCCP) Regional Experiment (FIRE) Water Vapor Experiment (AFWEX), the latter of which switched the focus to characterizing upper-tropospheric humidity measurements.