| 1. |
- Blokland, G. A. M., et al.
(författare)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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| 2. |
- 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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| 3. |
- Bryois, J., et al.
(författare)
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Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease
- 2020
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:5, s. 482-493
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson’s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson’s disease. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
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| 4. |
- Watson, H. J., et al.
(författare)
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Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa
- 2019
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:8
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Tidskriftsartikel (refereegranskat)abstract
- Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness(1), affecting 0.9-4% of women and 0.3% of men(2-4), with twin-based heritability estimates of 50-60%(5). Mortality rates are higher than those in other psychiatric disorders(6), and outcomes are unacceptably poor(7). Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)(8,9) and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.
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| 5. |
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| 6. |
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| 7. |
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| 8. |
- Doornenbal, P., et al.
(författare)
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RISING: Gamma‐ray Spectroscopy with Radioactive Beams at GSI
- 2007
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Ingår i: AIP Conference Proceedings. - : AIP. - 0094-243X. - 9780735413283 ; 891, s. 99-107
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Konferensbidrag (refereegranskat)abstract
- The Rare Isotope Spectroscopic INvestigation at GSI (RISING) project is a major pan‐European collaboration. Its physics aims are the studies of exotic nuclear matter with abnormal proton‐to‐neutron ratios compared with naturally occurring isotopes. RISING combines the FRagment Separator (FRS) which allows relativistic energies and projectile fragmentation reactions with EUROBALL Ge Cluster detectors for γ spectroscopic research. The RISING setup can be used in two different configurations. Either the nuclei of interest are investigated after being stopped or the heavy ions hit a secondary target at relativistic energies and the thereby occurring excitations are studied. For the latter case, MINIBALL Ge detectors and the HECTOR array are used in addition. Example achievements of the Fast Beam setup are presented and compared to various shell model calculations, while for the Stopped Beam setup initial results are shown.
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| 9. |
- Mason, P, et al.
(författare)
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Octupole signatures in Ba-124,Ba-125
- 2005
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Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 31:10, s. S1729-S1733
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Tidskriftsartikel (refereegranskat)abstract
- The gamma decay of the nuclei Ba-121,Ba-125 has been investigated with the EUROBALL array, using the reaction Ni-64+Ni-64 at E-beam = 255 and 261 MeV. Six new E1 transitions have been found in the nucleus Ba-125, suggesting a significant role of octupole correlations in the origin of its parity doublets. The J(pi) = 3(-) level of the nucleus Ba-124 has been identified for the first time. Its excitation energy is in very good agreement with a prediction based on a microscopic model including octupole interactions.
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| 10. |
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| 11. |
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| 12. |
- Yadav, R. B., et al.
(författare)
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Identification of triaxial strongly deformed bands in Hf-168
- 2008
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 78:4
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Tidskriftsartikel (refereegranskat)abstract
- Possible decay pathways associated with three candidates for triaxial strongly deformed (TSD) bands in Hf-168 have been investigated. The spin and excitation energy of the strongest band, TSD1, were determined approximately based on gamma-ray coincidence relationships. Discrete links were established for the second band. The overall agreement between the observed properties of the bands and cranking calculations using the ULTIMATE CRANKER code provides strong support for an interpretation where band TSD1 is associated with a TSD minimum, (epsilon(2),gamma)similar to(0.43,20(degrees)), involving the pi(i(13/2))(2) and the nu(j(15/2)) high-j orbitals. This constitutes the first identification of a TSD band in Hf isotopes, which has been long-predicted by theoretical studies. The second band is understood as being associated with a near-prolate shape and a deformation enhanced with respect to the normal deformed bands. It is proposed to be built on the pi(i(13/2)h(9/2))circle times nu(i(13/2))(2) configuration.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
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| 17. |
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| 18. |
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| 19. |
- Johansson, Therese, et al.
(författare)
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Polygenic association with severity and long-term outcome in eating disorder cases
- 2022
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- About 20% of individuals with anorexia nervosa (AN) remain chronically ill. Therefore, early identification of poor outcome could improve care. Genetic research has identified regions of the genome associated with AN. Patients with anorexia nervosa were identified via the Swedish eating disorder quality registers Stepwise and Riksat and invited to participate in the Anorexia Nervosa Genetics Initiative. First, we associated genetic information longitudinally with eating disorder severity indexed by scores on the Clinical Impairment Assessment (CIA) in 2843 patients with lifetime AN with or without diagnostic migration to other forms of eating disorders followed for up to 16 years (mean = 5.3 years). Second, we indexed the development of a severe and enduring eating disorder (SEED) by a high CIA score plus a follow-up time >= 5 years. We associated individual polygenic scores (PGSs) indexing polygenic liability for AN, schizophrenia, and body mass index (BMI) with severity and SEED. After multiple testing correction, only the BMI PGS when calculated with traditional clumping and p value thresholding was robustly associated with disorder severity (beta(PGS) = 1.30; 95% CI: 0.72, 1.88; p = 1.2 x 10(-5)) across all p value thresholds at which we generated the PGS. However, using the alternative PGS calculation method PRS-CS yielded inconsistent results for all PGS. The positive association stands in contrast to the negative genetic correlation between BMI and AN. Larger discovery GWASs to calculate PGS will increase power, and it is essential to increase sample sizes of the AN GWASs to generate clinically meaningful PGS as adjunct risk prediction variables. Nevertheless, this study provides the first evidence of potential clinical utility of PGSs for eating disorders.
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| 20. |
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| 21. |
- Nilsson, I. A. K., et al.
(författare)
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Aberrant inflammatory profile in acute but not recovered anorexia nervosa
- 2020
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Ingår i: Brain Behavior and Immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 88, s. 718-724
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Tidskriftsartikel (refereegranskat)abstract
- Anorexia nervosa (AN) is a severe psychiatric disorder with high mortality and relapse rates. Even though changes in inflammatory markers and cytokines are known to accompany cachexia associated with somatic disorders such as cancer and chronic kidney disorder, studies on inflammatory markers in AN are rare and typically include few individuals. Here, we utilize an Olink Proteomics inflammatory panel to explore the concentrations of 92 preselected inflammation-related proteins in plasma samples from women with active AN (N = 113), recovered from AN (AN-REC, N = 113), and normal weight healthy controls (N = 114). After correction for multiple testing, twenty-five proteins differed significantly between the AN group and controls (lower levels: ADA, CCL19, CD40, CD5, CD8A, CSF1, CXCL1, CXCL5, HGF, IL10RB, IL12B, 1L18R1, LAP TGF beta 1, MCP3, OSM, TGF alpha, TNFRSF9, TNFS14 and TRANCE; higher levels: CCL11, CCL25, CST5, DNER, LIFR and OPG). Although more than half of these differences (N=15) were present in the comparison between AN and AN-REC, no significant differences were seen between AN-REC and controls. Furthermore, twenty-five proteins correlated positively with BMI (ADA, AXIN1, CASP8, CD5, CD40, CSF1, CXCL1, CXCL5, EN-RAGE, HGF, IL6, IL10RB, IL12B, IL18, IL18R1, LAP TGF beta 1, OSM, SIRT2, STAMBP, TGF alpha, TNFRSF9, TNFS14, TRANCE, TRAIL and VEGFA) and four proteins correlated negatively with BMI (CCL11, CCL25, CCL28 and DNER). These results suggest that a dysregulated inflammatory status is associated with AN, but, importantly, seem to be confined to the acute illness state.
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| 22. |
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| 23. |
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| 24. |
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| 25. |
- Wollersheim, HJ, et al.
(författare)
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Rare ISotopes INvestigation at GSI (RISING) Using Gamma-ray Spectroscopy at Relativistic Energies
- 2005
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002. ; 537:3, s. 637-657
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Tidskriftsartikel (refereegranskat)abstract
- The Rare ISotopes INvestigation at GSI project combines the former EUROBALL Ge-Cluster detectors, the MINIBALL Ge detectors, BaF2--HECTOR detectors, and the fragment separator at GSI for high-resolution in-beam gamma-ray spectroscopy measurements with radioactive beams. These secondary beams produced at relativistic energies are used for Coulomb excitation or secondary fragmentation experiments in order to explore the nuclear structure of the projectiles or projectile like nuclei by measuring de-excitation photons. The newly designed detector array is described and the performance characteristics are given. Moreover, particularities of the experimental technique are discussed.
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| 26. |
- Abbaspour, A, et al.
(författare)
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Comparison of Dual-Energy X-ray Absorptiometry and Bioelectrical Impedance Analysis in the Assessment of Body Composition in Women with Anorexia Nervosa upon Admission and Discharge from an Inpatient Specialist Unit
- 2021
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Ingår i: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 18:21
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Tidskriftsartikel (refereegranskat)abstract
- Assessment of body composition is fundamental in diagnosis and treatment of anorexia nervosa (AN). The gold standard dual-energy X-ray absorptiometry (DXA) is expensive and not universally available. Bioelectrical impedance analysis (BIA) is a non-invasive, inexpensive method relative to DXA. We compared DXA and BIA in the assessment of fat-free mass (FFM), fat mass (FM), and body fat percentage (BF%) in women with AN upon admission (ANT1) and discharge (ANT2) from an inpatient specialist unit with a referent healthy control (HC) group. The study population consisted of 31 ANT1, 25 ANT2, and 52 HC women with median age of 21 years. Body composition was measured by DXA and Tanita foot-to-foot BIA. Comparison between the two methods was done using Bland–Altman analysis, Pearson’s correlation coefficient, Lin’s concordance correlation coefficient, and linear regression. The mean difference (bias) in FM and BF% values obtained by DXA and BIA in ANT1 (FM: +1.01 kg, BF%: +2.26%) and ANT2 (FM: +1.49 kg, BF%: +1.66%) were comparable to HC (FM: −1.32 kg, BF%: −2.29%) although in opposite directions. Less bias was observed in FFM values in ANT1 (−0.46 kg) and ANT2 (−0.86 kg) than in HC (+2.03 kg); however, the limits of agreement between the two methods were wider in ANT1 and ANT2 than in HC for all measurements. No association was observed between age, percentage of total body water, and the time spent on the inpatient specialist unit with the difference in estimates of body composition between DXA and BIA. Comparison of DXA and BIA suggests that DXA should remain the gold standard for measuring body composition; the development of more specific BIA equations is required to improve validity and precision of BIA in patients with AN. Despite ease and cost in both BIA access and operation, the suitability of BIA in a low bodyweight eating disorders population remains questionable.
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| 27. |
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| 28. |
- Abdulkadir, M, et al.
(författare)
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Polygenic Score for Body Mass Index Is Associated with Disordered Eating in a General Population Cohort
- 2020
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 9:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Disordered eating (DE) is common and is associated with body mass index (BMI). We investigated whether genetic variants for BMI were associated with DE. Methods: BMI polygenic scores (PGS) were calculated for participants of the Avon Longitudinal Study of Parents and Children (ALSPAC; N = 8654) and their association with DE tested. Data on DE behaviors (e.g., binge eating and compensatory behaviors) were collected at ages 14, 16, 18 years, and DE cognitions (e.g., body dissatisfaction) at 14 years. Mediation analyses determined whether BMI mediated the association between the BMI-PGS and DE. Results: The BMI-PGS was positively associated with fasting (OR = 1.42, 95% CI = 1.25, 1.61), binge eating (OR = 1.28, 95% CI = 1.12, 1.46), purging (OR = 1.20, 95% CI = 1.02, 1.42), body dissatisfaction (Beta = 0.99, 95% CI = 0.77, 1.22), restrained eating (Beta = 0.14, 95% CI = 0.10, 1.17), emotional eating (Beta = 0.21, 95% CI = 0.052, 0.38), and negatively associated with thin ideal internalization (Beta = −0.15, 95% CI = −0.23, −0.07) and external eating (Beta = −0.19, 95% CI = −0.30, −0.09). These associations were mainly mediated by BMI. Conclusions: Genetic variants associated with BMI are also associated with DE. This association was mediated through BMI suggesting that weight potentially sits on the pathway from genetic liability to DE.
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| 29. |
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| 30. |
- Becker, F, et al.
(författare)
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Status of the RISING Project at GSI
- 2005
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Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001. ; 25:Suppl 1, s. 719-722
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Tidskriftsartikel (refereegranskat)abstract
- The FRS-RISING set-up at GSI uses secondary radioactive beams at relativistic energies for nuclear structure studies. At GSI the fragmentation or fission of stable primary beams up to U-238 provide secondary beams with sufficient intensity to perform gamma-ray spectroscopy. The RISING set-up is described and results of the first RISING campaign are presented. New experimental methods at relativistic energies are being investigated. Future experiments focus on state-of-the art nuclear structure physics covering exotic nuclei all over the nuclear chart.
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| 31. |
- Bednarczyk, P, et al.
(författare)
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Status of the RISING Project at Relativistic Energies
- 2005
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Ingår i: Acta Physica Polonica. Series B: Elementary Particle Physics, Nuclear Physics, Statistical Physics, Theory of Relativity, Field Theory. - 0587-4254. ; 36:4, s. 1235-1244
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Tidskriftsartikel (refereegranskat)abstract
- The RISING project was designed to perform high-resolution gamma-ray spectroscopy with radioactive beams at GSI. Unstable beams were produced by fragmentation of relativistic heavy ion projectiles provided by the SIS synchrotron. The fragment separator FRS was used to select and to focus the exotic fragments at about 100A MeV energy on a secondary target. Various charged particle detectors enabled an event-by-event tracking of the incoming radioactive projectiles and the reaction products, thus allowing for a selection of the nuclei of interest and their velocity vector reconstruction. The gamma-ray detection system consisting of the EUROBALL Cluster Ge detectors and the large volume HECTOR BaF2 detectors measured prompt gamma-radiation from nuclei excited in the secondary target. Despite the huge Doppler shift due to the high recoil velocity (beta approximate to 40%), RISING achieved a gamma-energy resolution below 2%. The paper reviews the present status of the RISING project.
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| 32. |
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| 33. |
- CLARK, RM, et al.
(författare)
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A PAIR OF IDENTICAL SUPERDEFORMED BANDS IN ND-136
- 1995
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Ingår i: Physics Letters B. - 0370-2693 .- 1873-2445. ; 343:1-4, s. 59-63
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Tidskriftsartikel (refereegranskat)abstract
- High-spin states in Nd-136 were populated via the Mo-100(Ar-40, 4n) reaction at beam energies of 176 and 182 MeV, and resulting gamma-rays were detected using the GAMMASPHERE spectrometer. Analysis of the data has revealed the existence of an excited superdeformed (SD) band in Nd-136. Th, yrast SD band in Nd-136 has been extended by the addition of four (possibly five) transitions at high frequency. The new band displays the remarkable property of having transition energies identical (to within +/- 1 keV) to those of the half-points of the yrast SD band of Nd-136. Possible explanations in terms of cranked Woods-Saxon single-particle calculations are discussed.
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| 34. |
- DELEPLANQUE, MA, et al.
(författare)
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LOW-SPIN TERMINATION OF THE SUPERDEFORMED BAND IN ND-135
- 1995
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 52:5, s. R2302-R2305
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Tidskriftsartikel (refereegranskat)abstract
- The decay of the superdeformed (SD) band in Nd-135 was studied with the early implementation of gamma-sphere. The results suggest that the SD band ''terminates'' at spin 25/2. This termination is explained by a change of the SD minimum toward a triaxial lower deformation. Ultimate cranker calculations with the i(13/2) orbital occupied relate this change to a shift of a proton and neutron pair out of deformation-driving Nilsson orbitals. This is a completely new and unexpected mechanism for the decay of SD bands.
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| 35. |
- Ferreira, DLS, et al.
(författare)
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Associations between Blood Metabolic Profile at 7 Years Old and Eating Disorders in Adolescence: Findings from the Avon Longitudinal Study of Parents and Children
- 2019
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Ingår i: Metabolites. - : MDPI AG. - 2218-1989. ; 9:9
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Tidskriftsartikel (refereegranskat)abstract
- Eating disorders are severe illnesses characterized by both psychiatric and metabolic factors. We explored the prospective role of metabolic risk in eating disorders in a UK cohort (n = 2929 participants), measuring 158 metabolic traits in non-fasting EDTA-plasma by nuclear magnetic resonance. We associated metabolic markers at 7 years (exposure) with risk for anorexia nervosa and binge-eating disorder (outcomes) at 14, 16, and 18 years using logistic regression adjusted for maternal education, child’s sex, age, body mass index, and calorie intake at 7 years. Elevated very low-density lipoproteins, triglycerides, apolipoprotein-B/A, and monounsaturated fatty acids ratio were associated with lower odds of anorexia nervosa at age 18, while elevated high-density lipoproteins, docosahexaenoic acid and polyunsaturated fatty acids ratio, and fatty acid unsaturation were associated with higher risk for anorexia nervosa at 18 years. Elevated linoleic acid and n-6 fatty acid ratios were associated with lower odds of binge-eating disorder at 16 years, while elevated saturated fatty acid ratio was associated with higher odds of binge-eating disorder. Most associations had large confidence intervals and showed, for anorexia nervosa, different directions across time points. Overall, our results show some evidence for a role of metabolic factors in eating disorders development in adolescence.
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| 36. |
- Gaspar, HA, et al.
(författare)
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Using genetic drug-target networks to develop new drug hypotheses for major depressive disorder
- 2019
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1, s. 117-
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Tidskriftsartikel (refereegranskat)abstract
- The major depressive disorder (MDD) working group of the Psychiatric Genomics Consortium (PGC) has published a genome-wide association study (GWAS) for MDD in 130,664 cases, identifying 44 risk variants. We used these results to investigate potential drug targets and repurposing opportunities. We built easily interpretable bipartite drug-target networks integrating interactions between drugs and their targets, genome-wide association statistics, and genetically predicted expression levels in different tissues, using the online tool Drug Targetor (drugtargetor.com). We also investigated drug-target relationships that could be impacting MDD. MAGMA was used to perform pathway analyses and S-PrediXcan to investigate the directionality of tissue-specific expression levels in patients vs. controls. Outside the major histocompatibility complex (MHC) region, 153 protein-coding genes are significantly associated with MDD in MAGMA after multiple testing correction; among these, five are predicted to be down or upregulated in brain regions and 24 are known druggable genes. Several drug classes were significantly enriched, including monoamine reuptake inhibitors, sex hormones, antipsychotics, and antihistamines, indicating an effect on MDD and potential repurposing opportunities. These findings not only require validation in model systems and clinical examination, but also show that GWAS may become a rich source of new therapeutic hypotheses for MDD and other psychiatric disorders that need new—and better—treatment options.
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| 37. |
- Herle, M, et al.
(författare)
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A longitudinal study of eating behaviours in childhood and later eating disorder behaviours and diagnoses
- 2020
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Ingår i: The British journal of psychiatry : the journal of mental science. - : Royal College of Psychiatrists. - 1472-1465. ; 216:2, s. 113-119
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Tidskriftsartikel (refereegranskat)abstract
- Eating behaviours in childhood are considered as risk factors for eating disorder behaviours and diagnoses in adolescence. However, few longitudinal studies have examined this association.AimsWe investigated associations between childhood eating behaviours during the first ten years of life and eating disorder behaviours (binge eating, purging, fasting and excessive exercise) and diagnoses (anorexia nervosa, binge eating disorder, purging disorder and bulimia nervosa) at 16 years.MethodData on 4760 participants from the Avon Longitudinal Study of Parents and Children were included. Longitudinal trajectories of parent-rated childhood eating behaviours (8 time points, 1.3–9 years) were derived by latent class growth analyses. Eating disorder diagnoses were derived from self-reported, parent-reported and objectively measured anthropometric data at age 16 years. We estimated associations between childhood eating behaviours and eating disorder behaviours and diagnoses, using multivariable logistic regression models.ResultsChildhood overeating was associated with increased risk of adolescent binge eating (risk difference, 7%; 95% CI 2 to 12) and binge eating disorder (risk difference, 1%; 95% CI 0.2 to 3). Persistent undereating was associated with higher anorexia nervosa risk in adolescent girls only (risk difference, 6%; 95% CI, 0 to 12). Persistent fussy eating was associated with greater anorexia nervosa risk (risk difference, 2%; 95% CI 0 to 4).ConclusionsOur results suggest continuities of eating behaviours into eating disorders from early life to adolescence. It remains to be determined whether childhood eating behaviours are an early manifestation of a specific phenotype or whether the mechanisms underlying this continuity are more complex. Findings have the potential to inform preventative strategies for eating disorders.
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| 38. |
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| 39. |
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| 40. |
- Herle, M, et al.
(författare)
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Identifying typical trajectories in longitudinal data: modelling strategies and interpretations
- 2020
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Ingår i: European journal of epidemiology. - : Springer Science and Business Media LLC. - 1573-7284 .- 0393-2990. ; 35:3, s. 205-222
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Tidskriftsartikel (refereegranskat)abstract
- Individual-level longitudinal data on biological, behavioural, and social dimensions are becoming increasingly available. Typically, these data are analysed using mixed effects models, with the result summarised in terms of an average trajectory plus measures of the individual variations around this average. However, public health investigations would benefit from finer modelling of these individual variations which identify not just one average trajectory, but several typical trajectories. If evidence of heterogeneity in the development of these variables is found, the role played by temporally preceding (explanatory) variables as well as the potential impact of differential trajectories may have on later outcomes is often of interest. A wide choice of methods for uncovering typical trajectories and relating them to precursors and later outcomes exists. However, despite their increasing use, no practical overview of these methods targeted at epidemiological applications exists. Hence we provide: (a) a review of the three most commonly used methods for the identification of latent trajectories (growth mixture models, latent class growth analysis, and longitudinal latent class analysis); and (b) recommendations for the identification and interpretation of these trajectories and of their relationship with other variables. For illustration, we use longitudinal data on childhood body mass index and parental reports of fussy eating, collected in the Avon Longitudinal Study of Parents and Children.
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| 41. |
- Herle, M, et al.
(författare)
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The genomics of childhood eating behaviours
- 2021
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Ingår i: Nature human behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 5:5, s. 625-630
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Tidskriftsartikel (refereegranskat)
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| 42. |
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| 43. |
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| 44. |
- Hubel, C, et al.
(författare)
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Childhood overeating is associated with adverse cardiometabolic and inflammatory profiles in adolescence
- 2021
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 12478-
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Tidskriftsartikel (refereegranskat)abstract
- Childhood eating behaviour contributes to the rise of obesity and related noncommunicable disease worldwide. However, we lack a deep understanding of biochemical alterations that can arise from aberrant eating behaviour. In this study, we prospectively associate longitudinal trajectories of childhood overeating, undereating, and fussy eating with metabolic markers at age 16 years to explore adolescent metabolic alterations related to specific eating patterns in the first 10 years of life. Data are from the Avon Longitudinal Study of Parents and Children (n = 3104). We measure 158 metabolic markers with a high-throughput (1H) NMR metabolomics platform. Increasing childhood overeating is prospectively associated with an adverse cardiometabolic profile (i.e., hyperlipidemia, hypercholesterolemia, hyperlipoproteinemia) in adolescence; whereas undereating and fussy eating are associated with lower concentrations of the amino acids glutamine and valine, suggesting a potential lack of micronutrients. Here, we show associations between early behavioural indicators of eating and metabolic markers.
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| 45. |
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| 46. |
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| 47. |
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| 48. |
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| 49. |
- Hubel, C, et al.
(författare)
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Genetic correlations of psychiatric traits with body composition and glycemic traits are sex- and age-dependent
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 5765-
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Tidskriftsartikel (refereegranskat)abstract
- Body composition is often altered in psychiatric disorders. Using genome-wide common genetic variation data, we calculate sex-specific genetic correlations amongst body fat %, fat mass, fat-free mass, physical activity, glycemic traits and 17 psychiatric traits (up to N = 217,568). Two patterns emerge: (1) anorexia nervosa, schizophrenia, obsessive-compulsive disorder, and education years are negatively genetically correlated with body fat % and fat-free mass, whereas (2) attention-deficit/hyperactivity disorder (ADHD), alcohol dependence, insomnia, and heavy smoking are positively correlated. Anorexia nervosa shows a stronger genetic correlation with body fat % in females, whereas education years is more strongly correlated with fat mass in males. Education years and ADHD show genetic overlap with childhood obesity. Mendelian randomization identifies schizophrenia, anorexia nervosa, and higher education as causal for decreased fat mass, with higher body fat % possibly being a causal risk factor for ADHD and heavy smoking. These results suggest new possibilities for targeted preventive strategies.
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| 50. |
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