| 1. |
- Joshi, Peter K, et al.
(författare)
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Directional dominance on stature and cognition in diverse human populations
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
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Tidskriftsartikel (refereegranskat)abstract
- Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
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| 2. |
- Saleheen, Danish, et al.
(författare)
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Loss of Cardioprotective Effects at the ADAMTS7 Locus as a Result of Gene-Smoking Interactions
- 2017
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 135:24, s. 2336-2353
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Common diseases such as coronary heart disease (CHD) are complex in etiology. The interaction of genetic susceptibility with lifestyle factors may play a prominent role. However, gene-lifestyle interactions for CHD have been difficult to identify. Here, we investigate interaction of smoking behavior, a potent lifestyle factor, with genotypes that have been shown to associate with CHD risk.METHODS: We analyzed data on 60 919 CHD cases and 80 243 controls from 29 studies for gene-smoking interactions for genetic variants at 45 loci previously reported to be associated with CHD risk. We also studied 5 loci associated with smoking behavior. Study-specific gene-smoking interaction effects were calculated and pooled using fixed-effects meta-analyses. Interaction analyses were declared to be significant at a P value of < 1.0x10-3 (Bonferroni correction for 50 tests).RESULTS: We identified novel gene-smoking interaction for a variant upstream of the ADAMTS7 gene. Every T allele of rs7178051 was associated with lower CHD risk by 12% in never-smokers (P= 1.3x10(-16)) in comparison with 5% in ever-smokers (P= 2.5x10-4), translating to a 60% loss of CHD protection conferred by this allelic variation in people who smoked tobacco (interaction P value= 8.7x10-5). The protective T allele at rs7178051 was also associated with reduced ADAMTS7 expression in human aortic endothelial cells and lymphoblastoid cell lines. Exposure of human coronary artery smooth muscle cells to cigarette smoke extract led to induction of ADAMTS7.CONCLUSIONS: Allelic variation at rs7178051 that associates with reduced ADAMTS7 expression confers stronger CHD protection in never-smokers than in ever-smokers. Increased vascular ADAMTS7 expression may contribute to the loss of CHD protection in smokers.
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| 3. |
- Brierley, Chris M., et al.
(författare)
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Large-scale features and evaluation of the PMIP4-CMIP6 midHolocene simulations
- 2020
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 16:5, s. 1847-1872
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Tidskriftsartikel (refereegranskat)abstract
- The mid-Holocene (6000 years ago) is a standard time period for the evaluation of the simulated response of global climate models using palaeoclimate reconstructions. The latest mid-Holocene simulations are a palaeoclimate entry card for the Palaeoclimate Model Intercomparison Project (PMIP4) component of the current phase of the Coupled Model Intercomparison Project (CMIP6) - hereafter referred to as PMIP4-CMIP6. Here we provide an initial analysis and evaluation of the results of the experiment for the mid-Holocene. We show that state-of-the-art models produce climate changes that are broadly consistent with theory and observations, including increased summer warming of the Northern Hemisphere and associated shifts in tropical rainfall. Many features of the PMIP4-CMIP6 simulations were present in the previous generation (PMIP3-CMIP5) of simulations. The PMIP4-CMIP6 ensemble for the mid-Holocene has a global mean temperature change of -0.3 K, which is -0.2K cooler than the PMIP3-CMIP5 simulations predominantly as a result of the prescription of realistic greenhouse gas concentrations in PMIP4-CMIP6. Biases in the magnitude and the sign of regional responses identified in PMIP3-CMIP5, such as the amplification of the northern African monsoon, precipitation changes over Europe, and simulated aridity in mid-Eurasia, are still present in the PMIP4-CMIP6 simulations. Despite these issues, PMIP4-CMIP6 and the mid-Holocene provide an opportunity both for quantitative evaluation and derivation of emergent constraints on the hydrological cycle, feedback strength, and potentially climate sensitivity.
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| 4. |
- Brown, Josephine R., et al.
(författare)
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Comparison of past and future simulations of ENSO in CMIP5/PMIP3 and CMIP6/PMIP4 models
- 2020
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 16:5, s. 1777-1805
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Tidskriftsartikel (refereegranskat)abstract
- El Niño–Southern Oscillation (ENSO) is the strongest mode of interannual climate variability in the current climate, influencing ecosystems, agriculture, and weather systems across the globe, but future projections of ENSO frequency and amplitude remain highly uncertain. A comparison of changes in ENSO in a range of past and future climate simulations can provide insights into the sensitivity of ENSO to changes in the mean state, including changes in the seasonality of incoming solar radiation, global average temperatures, and spatial patterns of sea surface temperatures. As a comprehensive set of coupled model simulations is now available for both palaeoclimate time slices (the Last Glacial Maximum, mid-Holocene, and last interglacial) and idealised future warming scenarios (1 % per year CO2 increase, abrupt four-time CO2 increase), this allows a detailed evaluation of ENSO changes in this wide range of climates. Such a comparison can assist in constraining uncertainty in future projections, providing insights into model agreement and the sensitivity of ENSO to a range of factors. The majority of models simulate a consistent weakening of ENSO activity in the last interglacial and mid-Holocene experiments, and there is an ensemble mean reduction of variability in the western equatorial Pacific in the Last Glacial Maximum experiments. Changes in global temperature produce a weaker precipitation response to ENSO in the cold Last Glacial Maximum experiments and an enhanced precipitation response to ENSO in the warm increased CO2 experiments. No consistent relationship between changes in ENSO amplitude and annual cycle was identified across experiments.
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| 5. |
- Farnocchia, Davide, et al.
(författare)
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International Asteroid Warning Network Timing Campaign: 2019 XS
- 2022
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Ingår i: The Planetary Science Journal. - : Institute of Physics Publishing (IOPP). - 2632-3338. ; 3:7
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Tidskriftsartikel (refereegranskat)abstract
- As part of the International Asteroid Warning Network's observational exercises, we conducted a campaign to observe near-Earth asteroid 2019 XS around its close approach to Earth on 2021 November 9. The goal of the campaign was to characterize errors in the observation times reported to the Minor Planet Center, which become an increasingly important consideration as astrometric accuracy improves and more fast-moving asteroids are observed. As part of the exercise, a total of 957 astrometric observations of 2019 XS during the encounter were reported and subsequently were analyzed to obtain the corresponding residuals. While the timing errors are typically smaller than 1 s, the reported times appear to be negatively biased, i.e., they are generally earlier than they should be. We also compared the observer-provided position uncertainty with the cross-track residuals, which are independent of timing errors. A large fraction of the estimated uncertainties appear to be optimistic, especially when <0 2. We compiled individual reports for each observer to help identify and remove the root cause of any possible timing error and improve the uncertainty quantification process. We suggest possible sources of timing errors and describe a simple procedure to derive reliable, conservative position uncertainties.
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| 6. |
- Otto-Bliesner, Bette L., et al.
(författare)
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Large-scale features of Last Interglacial climate : results from evaluating the lig127k simulations for the Coupled Model Intercomparison Project (CMIP6)–Paleoclimate Modeling Intercomparison Project (PMIP4)
- 2021
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 17:1, s. 63-94
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Tidskriftsartikel (refereegranskat)abstract
- The modeling of paleoclimate, using physically based tools, is increasingly seen as a strong out-of-sample test of the models that are used for the projection of future climate changes. New to the Coupled Model Intercomparison Project (CMIP6) is the Tier 1 Last Interglacial experiment for 127 000 years ago (lig127k), designed to address the climate responses to stronger orbital forcing than the midHolocene experiment, using the same state-of-the-art models as for the future and following a common experimental protocol. Here we present a first analysis of a multi-model ensemble of 17 climate models, all of which have completed the CMIP6 DECK (Diagnostic, Evaluation and Characterization of Klima) experiments. The equilibrium climate sensitivity (ECS) of these models varies from 1.8 to 5.6 ∘C. The seasonal character of the insolation anomalies results in strong summer warming over the Northern Hemisphere continents in the lig127k ensemble as compared to the CMIP6 piControl and much-reduced minimum sea ice in the Arctic. The multi-model results indicate enhanced summer monsoonal precipitation in the Northern Hemisphere and reductions in the Southern Hemisphere. These responses are greater in the lig127k than the CMIP6 midHolocene simulations as expected from the larger insolation anomalies at 127 than 6 ka.New synthesis for surface temperature and precipitation, targeted for 127 ka, have been developed for comparison to the multi-model ensemble. The lig127k model ensemble and data reconstructions are in good agreement for summer temperature anomalies over Canada, Scandinavia, and the North Atlantic and for precipitation over the Northern Hemisphere continents. The model–data comparisons and mismatches point to further study of the sensitivity of the simulations to uncertainties in the boundary conditions and of the uncertainties and sparse coverage in current proxy reconstructions.The CMIP6–Paleoclimate Modeling Intercomparison Project (PMIP4) lig127k simulations, in combination with the proxy record, improve our confidence in future projections of monsoons, surface temperature, and Arctic sea ice, thus providing a key target for model evaluation and optimization.
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| 7. |
- Shi, Xiaoxu, et al.
(författare)
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Calendar effects on surface air temperature and precipitation based on model-ensemble equilibrium and transient simulations from PMIP4 and PACMEDY
- 2022
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 18:5, s. 1047-1070
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Tidskriftsartikel (refereegranskat)abstract
- Numerical modeling enables a comprehensive understanding not only of the Earth's system today, but also of the past. To date, a significant amount of time and effort has been devoted to paleoclimate modeling and analysis, which involves the latest and most advanced Paleoclimate Modelling Intercomparison Project phase 4 (PMIP4). The definition of seasonality, which is influenced by slow variations in the Earth's orbital parameters, plays a key role in determining the calculated seasonal cycle of the climate. In contrast to the classical calendar used today, where the lengths of the months and seasons are fixed, the angular calendar calculates the lengths of the months and seasons according to a fixed number of degrees along the Earth's orbit. When comparing simulation results for different time intervals, it is essential to account for the angular calendar to ensure that the data for comparison are from the same position along the Earth's orbit. Most models use the classical calendar, which can lead to strong distortions of the monthly and seasonal values, especially for the climate of the past. Here, by analyzing daily outputs from multiple PMIP4 model simulations, we examine calendar effects on surface air temperature and precipitation under mid-Holocene, Last Interglacial, and pre-industrial climate conditions. We came to the following conclusions. (a) The largest cooling bias occurs in boreal autumn when the classical calendar is applied for the mid-Holocene and Last Interglacial, due to the fact that the vernal equinox is fixed on 21 March. (b) The sign of the temperature anomalies between the Last Interglacial and pre-industrial in boreal autumn can be reversed after the switch from the classical to angular calendar, particularly over the Northern Hemisphere continents. (c) Precipitation over West Africa is overestimated in boreal summer and underestimated in boreal autumn when the classical seasonal cycle is applied. (d) Finally, month-length adjusted values for surface air temperature and precipitation are very similar to the day-length adjusted values, and therefore correcting the calendar based on the monthly model results can largely reduce the artificial bias. In addition, we examine the calendar effects in three transient simulations for 6-0 ka by AWIESM, MPI-ESM, and IPSL-CM. We find significant discrepancies between adjusted and unadjusted temperature values over continents for both hemispheres in boreal autumn, while for other seasons the deviations are relatively small. A drying bias can be found in the summer monsoon precipitation in Africa (in the classical calendar), whereby the magnitude of bias becomes smaller over time. Overall, our study underlines the importance of the application of calendar transformation in the analysis of climate simulations. Neglecting the calendar effects could lead to a profound artificial distortion of the calculated seasonal cycle of surface air temperature and precipitation.
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| 8. |
- van der Harst, Pim, et al.
(författare)
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Seventy-five genetic loci influencing the human red blood cell
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7429, s. 369-375
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Tidskriftsartikel (refereegranskat)abstract
- Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
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