Novel quantitative pigmentation phenotyping enhances genetic association, epistasis, and prediction of human eye colour

Success of genetic association and the prediction of phenotypic traits from DNA are known to depend on the accuracy of phenotype characterization, amongst other parameters. To overcome limitations in the characterization of human iris pigmentation, we introduce a fully automated approach that specifies the areal proportions proposed to represent differing pigmentation types, such as pheomelanin, eumelanin, and non-pigmented areas within the iris. We demonstrate the utility of this approach using high-resolution digital eye imagery and genotype data from 12 selected SNPs from over 3000 European samples of seven populations that are part of the EUREYE study. In comparison to previous quantification approaches, (1) we achieved an overall improvement in eye colour phenotyping, which provides a better separation of manually defined eye colour categories. (2) Single nucleotide polymorphisms (SNPs) known to be involved in human eye colour variation showed stronger associations with our approach. (3) We found new and confirmed previously noted SNP-SNP interactions. (4) We increased SNP-based prediction accuracy of quantitative eye colour. Our findings exemplify that precise quantification using the perceived biological basis of pigmentation leads to enhanced genetic association and prediction of eye colour. We expect our approach to deliver new pigmentation genes when applied to genome-wide association testing

Visual impairment and quality of life in the older European population, the EUREYE study.

PURPOSE: To determine the prevalence of visual impairment (VI) in populations 65 year or older from six European countries and describe the association with vision-related quality of life. VI was defined according to WHO as best corrected visual acuity 0,48 (World Health Organization (1992): International Statistical Classification of Diseases and Related Health Problems, 10th revised ed. Vol 1. Geneva). METHODS: 4166 participants in The European Eye study, 65 years and older selected randomly from the general census in the participating centres, were interviewed for vision-related quality of life and underwent an eye exam including distance visual acuity, refraction and fundus photography. RESULTS: The prevalence of VI rose with increasing age and more so in women. There was a pattern of a higher prevalence of VI in the Mediterranean countries compared to Northern European countries with the exception of Tallinn (Estonia) which had higher VI prevalence rates than the other north European centres. The prevalence of low vision was 3% or less in all centres. Blindness prevalence varied from 2% to less than half a per cent. Vision-related quality of life was strongly associated with visual acuity and the presence of bilateral age-related macular degeneration. CONCLUSION: The prevalence of visual impairment in the examined ageing European populations shows a definite increasing trend from north to south

DNA-based eye colour prediction across Europe with the IrisPlex system.

The ability to predict Externally Visible Characteristics (EVCs) from DNA, also referred to as Forensic DNA Phenotyping (FDP), is an exciting new chapter in forensic genetics holding great promise for tracing unknown individuals who are unidentifiable via standard forensic short tandem repeat (STR) profiling. For the purpose of DNA-based eye colour prediction, we previously developed the IrisPlex system consisting of a multiplex genotyping assay and a prediction model based on genotype and phenotype data from 3804 Dutch Europeans. Recently, we performed a forensic developmental validation study of the highly sensitive IrisPlex assay, which currently represents the only validated tool available for DNA-based prediction of eye colour in forensic applications. In the present study, we validate the IrisPlex prediction model by extending our initially described model towards genotype and phenotype data from multiple European populations. We performed IrisPlex analysis on 3840 individuals from seven sites across Europe as part of the European Eye (EUREYE) study for which DNA and high-resolution eye images were available. The accuracy rate of correctly predicting an individual's eye colour as being blue or brown, above the empirically established probability threshold of 0.7, was on average 94% across all seven European populations, ranging from 91% to 98%, despite the large variation in eye colour frequencies between the populations. The overall prediction accuracies expressed by the area under the receiver characteristic operating curves (AUC) were 0.96 for blue and 0.96 for brown eyes, which is considerably higher than those established before. The IrisPlex prediction model parameters generated from this multi-population European dataset, and thus its prediction capabilities, were highly comparable to those previously established. Therefore, the increased information regarding eye colour phenotype and genotype distributions across Europe, and the system's ability to provide eye colour predictions across Europe accurately, both highlight additional evidence for the utility of the IrisPlex system in forensic casework

Overview of the Norwegian Earth System Model (NorESM2) and key climate response of CMIP6 DECK, historical, and scenario simulations

The second version of the coupled Norwegian Earth System Model (NorESM2) is presented and evaluated. NorESM2 is based on the second version of the Community Earth System Model (CESM2) and shares with CESM2 the computer code infrastructure and many Earth system model components. However, NorESM2 employs entirely different ocean and ocean biogeochemistry models. The atmosphere component of NorESM2 (CAM-Nor) includes a different module for aerosol physics and chemistry, including interactions with cloud and radiation; additionally, CAM-Nor includes improvements in the formulation of local dry and moist energy conservation, in local and global angular momentum conservation, and in the computations for deep convection and air–sea fluxes. The surface components of NorESM2 have minor changes in the albedo calculations and to land and sea-ice models. We present results from simulations with NorESM2 that were carried out for the sixth phase of the Coupled Model Intercomparison Project (CMIP6). Two versions of the model are used: one with lower (∼ 2∘) atmosphere–land resolution and one with medium (∼ 1∘) atmosphere–land resolution. The stability of the pre-industrial climate and the sensitivity of the model to abrupt and gradual quadrupling of CO2 are assessed, along with the ability of the model to simulate the historical climate under the CMIP6 forcings. Compared to observations and reanalyses, NorESM2 represents an improvement over previous versions of NorESM in most aspects. NorESM2 appears less sensitive to greenhouse gas forcing than its predecessors, with an estimated equilibrium climate sensitivity of 2.5 K in both resolutions on a 150-year time frame; however, this estimate increases with the time window and the climate sensitivity at equilibration is much higher. We also consider the model response to future scenarios as defined by selected Shared Socioeconomic Pathways (SSPs) from the Scenario Model Intercomparison Project defined under CMIP6. Under the four scenarios (SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5), the warming in the period 2090–2099 compared to 1850–1879 reaches 1.3, 2.2, 3.0, and 3.9 K in NorESM2-LM, and 1.3, 2.1, 3.1, and 3.9 K in NorESM-MM, robustly similar in both resolutions. NorESM2-LM shows a rather satisfactory evolution of recent sea-ice area. In NorESM2-LM, an ice-free Arctic Ocean is only avoided in the SSP1-2.6 scenario

Overview of the Norwegian Earth System Model (NorESM2) and key climate response of CMIP6 DECK, historical, and scenario simulations

Abstract. The second version of the coupled Norwegian Earth System Model (NorESM2) is presented and evaluated. NorESM2 is based on the second version of the Community Earth System Model (CESM2) and shares with CESM2 the computer code infrastructure and many Earth system model components. However, NorESM2 employs entirely different ocean and ocean biogeochemistry models. The atmosphere component of NorESM2 (CAM-Nor) includes a different module for aerosol physics and chemistry, including interactions with cloud and radiation; additionally, CAM-Nor includes improvements in the formulation of local dry and moist energy conservation, in local and global angular momentum conservation, and in the computations for deep convection and air–sea fluxes. The surface components of NorESM2 have minor changes in the albedo calculations and to land and sea-ice models. We present results from simulations with NorESM2 that were carried out for the sixth phase of the Coupled Model Intercomparison Project (CMIP6). Two versions of the model are used: one with lower (∼ 2∘) atmosphere–land resolution and one with medium (∼ 1∘) atmosphere–land resolution. The stability of the pre-industrial climate and the sensitivity of the model to abrupt and gradual quadrupling of CO2 are assessed, along with the ability of the model to simulate the historical climate under the CMIP6 forcings. Compared to observations and reanalyses, NorESM2 represents an improvement over previous versions of NorESM in most aspects. NorESM2 appears less sensitive to greenhouse gas forcing than its predecessors, with an estimated equilibrium climate sensitivity of 2.5 K in both resolutions on a 150-year time frame; however, this estimate increases with the time window and the climate sensitivity at equilibration is much higher. We also consider the model response to future scenarios as defined by selected Shared Socioeconomic Pathways (SSPs) from the Scenario Model Intercomparison Project defined under CMIP6. Under the four scenarios (SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5), the warming in the period 2090–2099 compared to 1850–1879 reaches 1.3, 2.2, 3.0, and 3.9 K in NorESM2-LM, and 1.3, 2.1, 3.1, and 3.9 K in NorESM-MM, robustly similar in both resolutions. NorESM2-LM shows a rather satisfactory evolution of recent sea-ice area. In NorESM2-LM, an ice-free Arctic Ocean is only avoided in the SSP1-2.6 scenario

Complement factor H genetic variant and age-related macular degeneration:effect size, modifiers and relationship to disease subtype

Background: variation in the complement factor H gene (CFH) is associated with risk of late age-related macular degeneration (AMD). Previous studies have been case–control studies in populations of European ancestry with little differentiation in AMD subtype, and insufficient power to confirm or refute effect modification by smoking.Methods: to precisely quantify the association of the single nucleotide polymorphism (SNP rs1061170, ‘Y402H’) with risk of AMD among studies with differing study designs, participant ancestry and AMD grade and to investigate effect modification by smoking, we report two unpublished genetic association studies (n?=?2759) combined with data from 24 published studies (26 studies, 26?494 individuals, including 14?174 cases of AMD) of European ancestry, 10 of which provided individual-level data used to test gene–smoking interaction; and 16 published studies from non-European ancestry.Results: in individuals of European ancestry, there was a significant association between Y402H and late-AMD with a per-allele odds ratio (OR) of 2.27 [95% confidence interval (CI) 2.10–2.45; P?=?1.1?x?10?161]. There was no evidence of effect modification by smoking (P?=?0.75). The frequency of Y402H varied by ancestral origin and the association with AMD in non-Europeans was less clear, limited by paucity of studies.Conclusion: the Y402H variant confers a 2-fold higher risk of late-AMD per copy in individuals of European descent. This was stable to stratification by study design and AMD classification and not modified by smoking. The lack of association in non-Europeans requires further verification. These findings are of direct relevance for disease prediction. New research is needed to ascertain if differences in circulating levels, expression or activity of factor H protein explain the genetic associatio

Interactions between the atmosphere, cryosphere, and ecosystems at northern high latitudes

Abstract The Nordic Centre of Excellence CRAICC (Cryosphere–Atmosphere Interactions in a Changing Arctic Climate), funded by NordForsk in the years 2011–2016, is the largest joint Nordic research and innovation initiative to date, aiming to strengthen research and innovation regarding climate change issues in the Nordic region. CRAICC gathered more than 100 scientists from all Nordic countries in a virtual centre with the objectives of identifying and quantifying the major processes controlling Arctic warming and related feedback mechanisms, outlining strategies to mitigate Arctic warming, and developing Nordic Earth system modelling with a focus on short-lived climate forcers (SLCFs), including natural and anthropogenic aerosols. The outcome of CRAICC is reflected in more than 150 peer-reviewed scientific publications, most of which are in the CRAICC special issue of the journal Atmospheric Chemistry and Physics. This paper presents an overview of the main scientific topics investigated in the centre and provides the reader with a state-of-the-art comprehensive summary of what has been achieved in CRAICC with links to the particular publications for further detail. Faced with a vast amount of scientific discovery, we do not claim to completely summarize the results from CRAICC within this paper, but rather concentrate here on the main results which are related to feedback loops in climate change–cryosphere interactions that affect Arctic amplification