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- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 2. |
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| 3. |
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| 4. |
- Clark, DW, et al.
(författare)
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Associations of autozygosity with a broad range of human phenotypes
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4957-
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Tidskriftsartikel (refereegranskat)abstract
- In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
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| 5. |
- Lyons, PA, et al.
(författare)
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Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 5120-
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA.
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| 6. |
- Smith, Jennifer A, et al.
(författare)
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Genome-wide association study identifies 74 loci associated with educational attainment
- 2016
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Ingår i: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542
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Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
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| 7. |
- Walters, G. B., et al.
(författare)
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MAP1B mutations cause intellectual disability and extensive white matter deficit
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Discovery of coding variants in genes that confer risk of neurodevelopmental disorders is an important step towards understanding the pathophysiology of these disorders. Wholegenome sequencing of 31,463 Icelanders uncovers a frameshift variant (E712KfsTer10) in microtubule-associated protein 1B (MAP1B) that associates with ID/low IQ in a large pedigree (genome-wide corrected P = 0.022). Additional stop-gain variants in MAP1B (E1032Ter and R1664Ter) validate the association with ID and IQ. Carriers have 24% less white matter (WM) volume (beta = -2.1SD, P = 5.1 x 10(-8)), 47% less corpus callosum (CC) volume (beta = -2.4SD, P = 5.5 x 10(-10)) and lower brain-wide fractional anisotropy (P = 6.7 x 10(-4)). In summary, we show that loss of MAP1B function affects general cognitive ability through a profound, brain-wide WM deficit with likely disordered or compromised axons.
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| 8. |
- Gilbert, F., et al.
(författare)
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Sediment reworking by the burrowing polychaete Hediste diversicolor modulated by environmental and biological factors across the temperate North Atlantic. A tribute to Gaston Desrosiers
- 2021
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Ingår i: Journal of Experimental Marine Biology and Ecology. - : Elsevier BV. - 0022-0981. ; 541
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Tidskriftsartikel (refereegranskat)abstract
- Particle mixing and irrigation of the seabed by benthic fauna (bioturbation) have major impacts on ecosystem functions such as remineralization of organic matter and sediment-water exchange. As a tribute to Prof. Gaston Desrosiers by the Nereis Park association, eighteen laboratories carried out a collaborative experiment to acquire a global snapshot of particle reworking by the polychaete Hediste diversicolor at 16 sites surrounding the Northern Atlantic. Organisms and soft sediments were collected during May - July at different geographical locations and, using a common laboratory protocol, particulate fluorescent tracers (`luminophores') were used to quantify particle transport over a 10-day period. Particle mixing was quantified using the maximum penetration depth of tracers (MPD), particle diffusive coefficients (D-b), and non-local transport coefficients (r). Non-local coefficients (reflecting centimeter scale transport steps) ranged from 0.4 to 15 yr(-1), and were not correlated across sites with any measured biological (biomass, biovolume) or environmental parameters (temperature, grain size, organic matter). Maximum penetration depths (MPD) averaged similar to 10.7 cm (6.5-14.5 cm), and were similar to the global average bioturbation depth inferred from short-lived radiochemical tracers. MPD was also not correlated with measures of size (individual biomass), but increased with grain size and decreased with temperature. Bio-diffusion (D-b) correlated inversely with individual biomass (size) and directly with temperature over the environmental range (Q(10) similar to 1.7; 5-21 degrees C). The transport data were comparable in magnitude to rates reported for localized H. diversicolor populations of similar size, and confirmed some but not all correlations between sediment reworking and biological and environmental variables found in previous studies. The results imply that measures of particle reworking activities of a species from a single location can be generally extrapolated to different populations at similar conditions.
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| 9. |
- Gislason, S.R., et al.
(författare)
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Environmental pressure from the 2014–15 eruption of Bárðarbunga volcano, Iceland
- 2015
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Ingår i: Geochemical Perspectives Letters. - : European Association of Geochemistry. - 2410-3403 .- 2410-339X. ; 1:2015, s. 84 - 93
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Tidskriftsartikel (refereegranskat)abstract
- The effusive six months long 2014-2015 Bárðarbunga eruption (31 August-27 February) was the largest in Iceland for more than 200 years, producing 1.6 ± 0.3 km3 of lava. The total SO2 emission was 11 ± 5 Mt, more than the amount emitted from Europe in 2011. The ground level concentration of SO2 exceeded the 350 μg m−3 hourly average health limit over much of Iceland for days to weeks. Anomalously high SO2 concentrations were also measured at several locations in Europe in September. The lowest pH of fresh snowmelt at the eruption site was 3.3, and 3.2 in precipitation 105 km away from the source. Elevated dissolved H2SO4, HCl, HF, and metal concentrations were measured in snow and precipitation. Environmental pressures from the eruption and impacts on populated areas were reduced by its remoteness, timing, and the weather. The anticipated primary environmental pressure is on the surfacewaters, soils, and vegetation of Iceland.
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| 10. |
- Gunnarsson, Jonas S., et al.
(författare)
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Response of marine benthic fauna to thin-layer capping with activated carbon in a large-scale field experiment in the Grenland fjords, Norway
- 2017
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Ingår i: Environmental Science and Pollution Research. - : Springer Science and Business Media LLC. - 0944-1344 .- 1614-7499. ; 24:16, s. 14218-14233
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Tidskriftsartikel (refereegranskat)abstract
- A field experiment with thin-layer capping was conducted in the Grenland fjords, Norway, for remediation in situ of mercury and dioxin-contaminated sediments. Experimental fields at 30 and 95 m depth were capped with (i) powdered activated carbon (AC) mixed with clay (AC+clay), (ii) clay, and (iii) crushed limestone. Ecological effects on the benthic community and species-feeding guilds were studied 1 and 14 months after capping, and a total of 158 species were included in the analyses. The results show that clay and limestone had only minor effects on the benthic community, while AC+clay caused severe perturbations. AC+clay reduced the abundance, biomass, and number of species by up to 90% at both 30 and 95 m depth, and few indications of recovery were found during the period of this investigation. The negative effects of AC+clay were observed on a wide range of species with different feeding strategies, although the suspension feeding brittle star Amphiura filiformis was particularly affected. Even though activated carbon is effective in reducing sediment-to-water fluxes of dioxins and other organic pollutants, this study shows that capping with powdered AC can lead to substantial disturbances to the benthic community.
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