| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Liu, Xueping, et al.
(författare)
-
Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration.
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P=3.96×10-14). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Evans, Brittany, et al.
(författare)
-
Urbanicity is Associated with Behavioral and Emotional Problems in Elementary School-Aged Children
- 2018
-
Ingår i: Journal of Child and Family Studies. - : Springer Science and Business Media LLC. - 1062-1024 .- 1573-2843. ; 27:7, s. 2193-2205
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract: Adults are 38% more likely to suffer from a psychiatric disorder when they live in an urban compared to a rural area. Urban upbringing may be particularly important. The aim of the present study was to examine whether urbanicity was independently associated with mental health in elementary school-aged children. Specifically, we investigated whether living in a more urban area was associated with exhibiting more behavioral and emotional problems, and whether this remained while controlling for other major risk factors for mental health problems in children. Data came from a Dutch general population study of children (n = 895). Information from four waves was used, in which children were aged approximately 8, 9, 11, and 12 years old. We used mixed effects models to assess the association between urbanicity and the outcomes of behavioral problems and emotional problems separately, while controlling for other major risk factors. The analyses showed that children who lived in more urban areas were significantly more likely to exhibit behavioral (p < .001) and emotional (p < .001) problems. This effect remained when controlling for neighborhood socioeconomic status, gender, ethnicity, family socioeconomic status, parental symptoms of psychopathology, parenting stress, and parenting practices (behavioral: p = .02, emotional: p = .009). In line with research in adults, urbanicity seems to be independently associated with behavioral and emotional problems in children. A possible underlying mechanism is that the city is a stressful environment for children to grow up in, which contributes to an increased risk for mental health problems.
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
- Rajagopal, VM, et al.
(författare)
-
Genome-wide association study of school grades identifies genetic overlap between language ability, psychopathology and creativity
- 2023
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 13:1, s. 429-
-
Tidskriftsartikel (refereegranskat)abstract
- Cognitive functions of individuals with psychiatric disorders differ from that of the general population. Such cognitive differences often manifest early in life as differential school performance and have a strong genetic basis. Here we measured genetic predictors of school performance in 30,982 individuals in English, Danish and mathematics via a genome-wide association study (GWAS) and studied their relationship with risk for six major psychiatric disorders. When decomposing the school performance into math and language-specific performances, we observed phenotypically and genetically a strong negative correlation between math performance and risk for most psychiatric disorders. But language performance correlated positively with risk for certain disorders, especially schizophrenia, which we replicate in an independent sample (n = 4547). We also found that the genetic variants relating to increased risk for schizophrenia and better language performance are overrepresented in individuals involved in creative professions (n = 2953) compared to the general population (n = 164,622). The findings together suggest that language ability, creativity and psychopathology might stem from overlapping genetic roots.
|
|
| 16. |
- Bryois, J, et al.
(författare)
-
Evaluation of chromatin accessibility in prefrontal cortex of individuals with schizophrenia
- 2018
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 3121-
-
Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia genome-wide association studies have identified >150 regions of the genome associated with disease risk, yet there is little evidence that coding mutations contribute to this disorder. To explore the mechanism of non-coding regulatory elements in schizophrenia, we performed ATAC-seq on adult prefrontal cortex brain samples from 135 individuals with schizophrenia and 137 controls, and identified 118,152 ATAC-seq peaks. These accessible chromatin regions in the brain are highly enriched for schizophrenia SNP heritability. Accessible chromatin regions that overlap evolutionarily conserved regions exhibit an even higher heritability enrichment, indicating that sequence conservation can further refine functional risk variants. We identify few differences in chromatin accessibility between cases and controls, in contrast to thousands of age-related differential accessible chromatin regions. Altogether, we characterize chromatin accessibility in the human prefrontal cortex, the effect of schizophrenia and age on chromatin accessibility, and provide evidence that our dataset will allow for fine mapping of risk variants.
|
|
| 17. |
- Finzell, Thomas, et al.
(författare)
-
A Detailed Observational Analysis of V1324 Sco, the Most Gamma-Ray-luminous Classical Nova to Date
- 2018
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 852:2
-
Tidskriftsartikel (refereegranskat)abstract
- It has recently been discovered that some, if not all, classical novae emit GeV gamma-rays during outburst, but the mechanisms involved in the production ofgamma-rays are still not well understood. We present here a comprehensive multiwavelength data set - from radio to X-rays - for the most gamma-ray-luminous classical nova to date, V1324 Sco. Using this data set, we show that V1324 Sco is a canonical dusty Fe ii-type nova, with a maximum ejecta velocity of 2600 km s-1 and an ejecta mass of a few × 10-5 M⊙. There is also evidence for complex shock interactions, including a double-peaked radio light curve which shows high brightness temperatures at early times. To explore why V1324 Sco was so gamma-ray luminous, we present a model of the nova ejecta featuring strong internal shocks and find that higher gamma-ray luminosities result from higher ejecta velocities and/or mass-loss rates. Comparison of V1324 Sco with other gamma-ray-detected novae does not show clear signatures of either, and we conclude that a larger sample of similarly well-observed novae is needed to understand the origin and variation of gamma-rays in novae.
|
|
| 18. |
- Freud, Lindsay R., et al.
(författare)
-
Prenatal vs postnatal diagnosis of 22q11.2 deletion syndrome: cardiac and noncardiac outcomes through 1 year of age
- 2024
-
Ingår i: American Journal of Obstetrics and Gynecology. - 0002-9378 .- 1097-6868. ; 230:3
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The 22q11.2 deletion syndrome is the most common microdeletion syndrome and is frequently associated with congenital heart disease. Prenatal diagnosis of 22q11.2 deletion syndrome is increasingly offered. It is unknown whether there is a clinical benefit to prenatal detection as compared with postnatal diagnosis. Objective: This study aimed to determine differences in perinatal and infant outcomes between patients with prenatal and postnatal diagnosis of 22q11.2 deletion syndrome. Study Design: This was a retrospective cohort study across multiple international centers (30 sites, 4 continents) from 2006 to 2019. Participants were fetuses, neonates, or infants with a genetic diagnosis of 22q11.2 deletion syndrome by 1 year of age with or without congenital heart disease; those with prenatal diagnosis or suspicion (suggestive ultrasound findings and/or high-risk cell-free fetal DNA screen for 22q11.2 deletion syndrome with postnatal confirmation) were compared with those with postnatal diagnosis. Perinatal management, cardiac and noncardiac morbidity, and mortality by 1 year were assessed. Outcomes were adjusted for presence of critical congenital heart disease, gestational age at birth, and site. Results: A total of 625 fetuses, neonates, or infants with 22q11.2 deletion syndrome (53.4% male) were included: 259 fetuses were prenatally diagnosed (156 [60.2%] were live-born) and 122 neonates were prenatally suspected with postnatal confirmation, whereas 244 infants were postnatally diagnosed. In the live-born cohort (n=522), 1-year mortality was 5.9%, which did not differ between groups but differed by the presence of critical congenital heart disease (hazard ratio, 4.18; 95% confidence interval, 1.56–11.18; P<.001) and gestational age at birth (hazard ratio, 0.78 per week; 95% confidence interval, 0.69–0.89; P<.001). Adjusting for critical congenital heart disease and gestational age at birth, the prenatal cohort was less likely to deliver at a local community hospital (5.1% vs 38.2%; odds ratio, 0.11; 95% confidence interval, 0.06–0.23; P<.001), experience neonatal cardiac decompensation (1.3% vs 5.0%; odds ratio, 0.11; 95% confidence interval, 0.03–0.49; P=.004), or have failure to thrive by 1 year (43.4% vs 50.3%; odds ratio, 0.58; 95% confidence interval, 0.36–0.91; P=.019). Conclusion: Prenatal detection of 22q11.2 deletion syndrome was associated with improved delivery management and less cardiac and noncardiac morbidity, but not mortality, compared with postnatal detection.
|
|
| 19. |
- Gomes, CPC, et al.
(författare)
-
Catalyzing Transcriptomics Research in Cardiovascular Disease: The CardioRNA COST Action CA17129
- 2019
-
Ingår i: Non-coding RNA. - : MDPI AG. - 2311-553X. ; 5:2
-
Tidskriftsartikel (refereegranskat)abstract
- Cardiovascular disease (CVD) remains the leading cause of death worldwide and, despite continuous advances, better diagnostic and prognostic tools, as well as therapy, are needed. The human transcriptome, which is the set of all RNA produced in a cell, is much more complex than previously thought and the lack of dialogue between researchers and industrials and consensus on guidelines to generate data make it harder to compare and reproduce results. This European Cooperation in Science and Technology (COST) Action aims to accelerate the understanding of transcriptomics in CVD and further the translation of experimental data into usable applications to improve personalized medicine in this field by creating an interdisciplinary network. It aims to provide opportunities for collaboration between stakeholders from complementary backgrounds, allowing the functions of different RNAs and their interactions to be more rapidly deciphered in the cardiovascular context for translation into the clinic, thus fostering personalized medicine and meeting a current public health challenge. Thus, this Action will advance studies on cardiovascular transcriptomics, generate innovative projects, and consolidate the leadership of European research groups in the field.COST (European Cooperation in Science and Technology) is a funding organization for research and innovation networks (www.cost.eu).
|
|
| 20. |
- Kim, Hyeongju, et al.
(författare)
-
A pathogenic proteolysis-resistant huntingtin isoform induced by an antisense oligonucleotide maintains huntingtin function
- 2022
-
Ingår i: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 7:17
-
Tidskriftsartikel (refereegranskat)abstract
- Huntington's disease (HD) is a late-onset neurological disorder for which therapeutics are not available. Its key pathological mechanism involves the proteolysis of polyglutamine-expanded (polyQ-expanded) mutant huntingtin (mHTT), which generates N-terminal fragments containing polyQ, a key contributor to HD pathogenesis. Interestingly, a naturally occurring spliced form of HTT mRNA with truncated exon 12 encodes an HTT (HTT & UDelta;12) with a deletion near the caspase-6 cleavage site. In this study, we used a multidisciplinary approach to characterize the therapeutic potential of targeting HTT exon 12. We show that HTT & UDelta;12 was resistant to caspase-6 cleavage in both cell-free and tissue lysate assays. However, HTT & UDelta;12 retained overall biochemical and structural properties similar to those of wt-HTT. We generated mice in which HTT exon 12 was truncated and found that the canonical exon 12 was dispensable for the main physiological functions of HTT, including embryonic development and intracellular trafficking. Finally, we pharmacologically induced HTT & UDelta;12 using the antisense oligonucleotide (ASO) QRX-704. QRX-704 showed predictable pharmacology and efficient biodistribution. In addition, it was stable for several months and inhibited pathogenic proteolysis. Furthermore, QRX-704 treatments resulted in a reduction of HTT aggregation and an increase in dendritic spine count. Thus, ASO-induced HTT exon 12 splice switching from HTT may provide an alternative therapeutic strategy for HD.
|
|
| 21. |
|
|
| 22. |
- Pasman, Joëlle A., et al.
(författare)
-
Epidemiological overview of major depressive disorder in Scandinavia using nationwide registers
- 2023
-
Ingår i: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 29
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Major depressive disorder (MDD) is a common psychiatric disorder associated with a high disease burden. This study gives a comprehensive overview of the prevalence, outcomes, treatment, and genetic epidemiology of MDD within and across the Scandinavian countries.METHODS: This study has aimed to assess and compare across Norway, Denmark, and Sweden 1) the prevalence and trajectories of MDD and comorbidity, 2) outcomes and treatment, and 3) heritability (Denmark and Sweden only). The analyses leveraged data on 272,944 MDD cases (and 6.2 million non-cases) from Norway, Sweden, and Denmark in specialist care in national longitudinal health registers covering 1975-2013. Relying on harmonized public data global comparisons of socioeconomic and health metrics were performed to assess to what extent findings are generalizable.FINDINGS: MDD ranked among the most prevalent psychiatric disorders. For many cases, the disorder trajectory was severe, with varying proportions experiencing recurrence, developing comorbid disorders, requiring inpatient treatment, or dying of suicide. Important country differences in specialist care prevalence and treatment were observed. Heritability estimates were moderate (35-48%). In terms of socioeconomic and health indices, the Scandinavian nations were comparable to one another and grouped with other Western nations.INTERPRETATION: The Scandinavian countries were similar with regards to MDD epidemiological measures, but we show that differences in health care organization need to be taken into consideration when comparing countries. This study demonstrates the utility of using comprehensive population-wide registry data, outlining possibilities for other applications. The findings will be of use to policy makers for developing better prevention and intervention strategies.
|
|
| 23. |
|
|
| 24. |
- Skotte, Line, et al.
(författare)
-
Genome-wide association study of febrile seizures implicates fever response and neuronal excitability genes
- 2022
-
Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 145:2, s. 555-568
-
Tidskriftsartikel (refereegranskat)abstract
- Febrile seizures represent the most common type of pathological brain activity in young children and are influenced by genetic, environmental and developmental factors. In a minority of cases, febrile seizures precede later development of epilepsy. We conducted a genome-wide association study of febrile seizures in 7635 cases and 83 966 controls identifying and replicating seven new loci, all with P < 5 × 10-10. Variants at two loci were functionally related to altered expression of the fever response genes PTGER3 and IL10, and four other loci harboured genes (BSN, ERC2, GABRG2, HERC1) influencing neuronal excitability by regulating neurotransmitter release and binding, vesicular transport or membrane trafficking at the synapse. Four previously reported loci (SCN1A, SCN2A, ANO3 and 12q21.33) were all confirmed. Collectively, the seven novel and four previously reported loci explained 2.8% of the variance in liability to febrile seizures, and the single nucleotide polymorphism heritability based on all common autosomal single nucleotide polymorphisms was 10.8%. GABRG2, SCN1A and SCN2A are well-established epilepsy genes and, overall, we found positive genetic correlations with epilepsies (rg = 0.39, P = 1.68 × 10-4). Further, we found that higher polygenic risk scores for febrile seizures were associated with epilepsy and with history of hospital admission for febrile seizures. Finally, we found that polygenic risk of febrile seizures was lower in febrile seizure patients with neuropsychiatric disease compared to febrile seizure patients in a general population sample. In conclusion, this largest genetic investigation of febrile seizures to date implicates central fever response genes as well as genes affecting neuronal excitability, including several known epilepsy genes. Further functional and genetic studies based on these findings will provide important insights into the complex pathophysiological processes of seizures with and without fever.
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
- Sorensen, SL, et al.
(författare)
-
Femtosecond pump-probe photoelectron spectroscopy of predissociative Rydberg states in acetylene
- 2000
-
Ingår i: JOURNAL OF CHEMICAL PHYSICS. - : AMER INST PHYSICS. - 0021-9606. ; 112:18, s. 8038-8042 Language: English
-
Tidskriftsartikel (refereegranskat)abstract
- We employ a pump-probe approach to molecular photoionization to study fast dissociation of Rydberg states in acetylene. By using time-resolved photoelectron spectroscopy to study the electronic state of the resulting ions we are able to monitor the system
|
|
| 28. |
- Sorensen, S. L., et al.
(författare)
-
Femtosecond pump-probe photoelectron spectroscopy of predissociative Rydberg states in acetylene
- 2000
-
Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 112:18, s. 8038-8042
-
Tidskriftsartikel (refereegranskat)abstract
- We employ a pump-probe approach to molecular photoionization to study fast dissociation of Rydberg states in acetylene. By using time-resolved photoelectron spectroscopy to study the electronic state of the resulting ions we are able to monitor the system continuously during dissociation or rearrangement. We find that the predissociative lifetime for the 3R‴ (v′2 = 1) Rydberg state is about 150 fs. We demonstrate a powerful new technique using time-correlated femtosecond harmonic generation and laser light pulses to study the time evolution of ultrafast dynamic processes in molecules.
|
|
