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- Munn-Chernoff, M. A., et al.
(författare)
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Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies
- 2021
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Ingår i: Addiction Biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 26:1
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Tidskriftsartikel (refereegranskat)abstract
- Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [r(g)], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from similar to 2400 to similar to 537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (r(g) = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (r(g) = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (r(g) = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (r(gs) = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.
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| 2. |
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| 3. |
- Apatenkov, S. V., et al.
(författare)
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Multi-spacecraft observation of plasma dipolarization/injection in the inner magnetosphere
- 2007
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Ingår i: Annales Geophysicae. - 0992-7689 .- 1432-0576. ; 25:3, s. 801-814
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Tidskriftsartikel (refereegranskat)abstract
- Addressing the origin of the energetic particle injections into the inner magnetosphere, we investigate the 23 February 2004 substorm using a favorable constellation of four Cluster (near perigee), LANL and Geotail spacecraft. Both an energy-dispersed and a dispersionless injection were observed by Cluster crossing the plasma sheet horn, which mapped to 9-12 R-E in the equatorial plane close to the midnight meridian. Two associated narrow equatorward auroral tongues/streamers propagating from the oval poleward boundary could be discerned in the global images obtained by IMAGE/WIC. As compared to the energy-dispersed event, the dispersionless injection front has important distinctions consequently repeated at 4 spacecraft: a simultaneous increase in electron fluxes at energies similar to 1.300 keV, similar to 25 nT increase in B-Z and a local increase by a factor 1.5-1.7 in plasma pressure. The injected plasma was primarily of solar wind origin. We evaluated the change in the injected flux tube configuration during the dipolarization by fitting flux increases observed by the PEACE and RAPID instruments, assuming adiabatic heating and the Liouville theorem. Mapping the locations of the injection front detected by the four spacecraft to the equatorial plane, we estimated the injection front thickness to be similar to 1 R-E and the earthward propagation speed to be similar to 200-400km/s (at 9-12 RE). Based on observed injection properties, we suggest that it is the underpopulated flux tubes (bubbles with enhanced magnetic field and sharp inner front propagating earthward), which accelerate and transport particles into the strong-field dipolar region.
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| 4. |
- Czamara, D, et al.
(författare)
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Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2548-
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Tidskriftsartikel (refereegranskat)abstract
- Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.
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| 7. |
- Middeldorp, Christel M., et al.
(författare)
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The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
- 2019
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
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Tidskriftsartikel (refereegranskat)abstract
- The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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| 8. |
- Pulkkinen, T. I., et al.
(författare)
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Magnetospheric modes and solar wind energy coupling efficiency
- 2010
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 115:3, s. A03207-
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Tidskriftsartikel (refereegranskat)abstract
- Using observations and two different global MHD simulations, we demonstrate that the solar wind speed controls the magnetospheric response such that the higher the speed, the more dynamic and irregular is the magnetospheric response. For similar level of driving solar wind electric field, the magnetospheric modes can be organized in terms of speed: Low speed produces steady convection events, intermediate speeds result in periodic sawtooth oscillations, and high speeds drive large geomagnetic storms. We show that the control parameter of energy transfer and coupling is the electric field along the large-scale X line. We demonstrate using global MHD simulations that for slowly varying interplanetary magnetic field (IMF), the reconnection line is tilted approximately by an angle theta/2, where theta is the IMF clock angle. Then, for clock angles away from northward, the magnetospheric energy entry and response scale with the electric field along the reconnection line (E-PAR), rather than the traditionally used E-Y. If we define the energy coupling efficiency as response/E-PAR, we can show it to be independent of the IMF clock angle and only weakly dependent on the solar wind dynamic pressure. These results demonstrate the ability of the localized reconnection line to control the energy input through the entire magnetopause.
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