| 1. |
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| 2. |
- MacLennan, Alastair H, et al.
(författare)
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Genetic or Other Causation Should Not Change the Clinical Diagnosis of Cerebral Palsy.
- 2019
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Ingår i: Journal of child neurology. - : SAGE Publications. - 1708-8283 .- 0883-0738. ; 38:4, s. 472-6
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Tidskriftsartikel (refereegranskat)abstract
- High throughput sequencing is discovering many likely causative genetic variants in individuals with cerebral palsy. Some investigators have suggested that this changes the clinical diagnosis of cerebral palsy and that these individuals should be removed from this diagnostic category. Cerebral palsy is a neurodevelopmental disorder diagnosed on clinical signs, not etiology. All nonprogressive permanent disorders of movement and posture attributed to disturbances that occurred in the developing fetal and infant brain can be described as "cerebral palsy." This definition of cerebral palsy should not be changed, whatever the cause. Reasons include stability, utility and accuracy of cerebral palsy registers, direct access to services, financial and social support specifically offered to families with cerebral palsy, and community understanding of the clinical diagnosis. Other neurodevelopmental disorders, for example, epilepsy, have not changed the diagnosis when genomic causes are found. The clinical diagnosis of cerebral palsy should remain, should prompt appropriate genetic studies and can subsequently be subclassified by etiology.
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| 3. |
- Sakabe, Noboru J, et al.
(författare)
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Transcriptome and regulatory maps of decidua-derived stromal cells inform gene discovery in preterm birth.
- 2020
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Ingår i: Science advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 6:49
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Tidskriftsartikel (refereegranskat)abstract
- While a genetic component of preterm birth (PTB) has long been recognized and recently mapped by genome-wide association studies (GWASs), the molecular determinants underlying PTB remain elusive. This stems in part from an incomplete availability of functional genomic annotations in human cell types relevant to pregnancy and PTB. We generated transcriptome (RNA-seq), epigenome (ChIP-seq of H3K27ac, H3K4me1, and H3K4me3 histone modifications), open chromatin (ATAC-seq), and chromatin interaction (promoter capture Hi-C) annotations of cultured primary decidua-derived mesenchymal stromal/stem cells and in vitro differentiated decidual stromal cells and developed a computational framework to integrate these functional annotations with results from a GWAS of gestational duration in 56,384 women. Using these resources, we uncovered additional loci associated with gestational duration and target genes of associated loci. Our strategy illustrates how functional annotations in pregnancy-relevant cell types aid in the experimental follow-up of GWAS for PTB and, likely, other pregnancy-related conditions.
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| 4. |
- Zhang, G., et al.
(författare)
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Genetic Associations with Gestational Duration and Spontaneous Preterm Birth
- 2017
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 377:12, s. 1156-1167
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Despite evidence that genetic factors contribute to the duration of gestation and the risk of preterm birth, robust associations with genetic variants have not been identified. We used large data sets that included the gestational duration to determine possible genetic associations. We performed a genomewide association study in a discovery set of samples obtained from 43,568 women of European ancestry using gestational duration as a continuous trait and term or preterm (< 37 weeks) birth as a dichotomous outcome. We used samples from three Nordic data sets (involving a total of 8643 women) to test for replication of genomic loci that had significant genomewide association (P< 5.0x10(-8)) or an association with suggestive significance (P< 1.0x10(-6)) in the discovery set. In the discovery and replication data sets, four loci (EBF1, EEFSEC, AGTR2, and WNT4) were significantly associated with gestational duration. Functional analysis showed that an implicated variant in WNT4 alters the binding of the estrogen receptor. The association between variants in ADCY5 and RAP2C and gestational duration had suggestive significance in the discovery set and significant evidence of association in the replication sets; these variants also showed genomewide significance in a joint analysis. Common variants in EBF1, EEFSEC, and AGTR2 showed association with preterm birth with genomewide significance. An analysis of mother-infant dyads suggested that these variants act at the level of the maternal genome. In this genomewide association study, we found that variants at the EBF1, EEFSEC, AGTR2, WNT4, ADCY5, and RAP2C loci were associated with gestational duration and variants at the EBF1, EEFSEC, and AGTR2 loci with preterm birth. Previously established roles of these genes in uterine development, maternal nutrition, and vascular control support their mechanistic involvement.
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| 5. |
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| 7. |
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| 8. |
- Plunkett, Jevon, et al.
(författare)
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Primate-specific evolution of noncoding element insertion into PLA2G4C and human preterm birth
- 2010
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Ingår i: BMC Medical Genomics. - : Springer Science and Business Media LLC. - 1755-8794. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Background: The onset of birth in humans, like other apes, differs from non-primate mammals in its endocrine physiology. We hypothesize that higher primate-specific gene evolution may lead to these differences and target genes involved in human preterm birth, an area of global health significance. Methods: We performed a comparative genomics screen of highly conserved noncoding elements and identified PLA2G4C, a phospholipase A isoform involved in prostaglandin biosynthesis as human accelerated. To examine whether this gene demonstrating primate-specific evolution was associated with birth timing, we genotyped and analyzed 8 common single nucleotide polymorphisms (SNPs) in PLA2G4C in US Hispanic (n = 73 preterm, 292 control), US White (n = 147 preterm, 157 control) and US Black (n = 79 preterm, 166 control) mothers. Results: Detailed structural and phylogenic analysis of PLA2G4C suggested a short genomic element within the gene duplicated from a paralogous highly conserved element on chromosome 1 specifically in primates. SNPs rs8110925 and rs2307276 in US Hispanics and rs11564620 in US Whites were significant after correcting for multiple tests (p < 0.006). Additionally, rs11564620 (Thr360Pro) was associated with increased metabolite levels of the prostaglandin thromboxane in healthy individuals (p = 0.02), suggesting this variant may affect PLA2G4C activity. Conclusions: Our findings suggest that variation in PLA2G4C may influence preterm birth risk by increasing levels of prostaglandins, which are known to regulate labor.
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| 9. |
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| 10. |
- Tsao, K., et al.
(författare)
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Effects of regional differences and demography in modelling foot-and-mouth disease in cattle at the national scale
- 2020
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Ingår i: Interface Focus. - : Royal Society Publishing. - 2042-8898 .- 2042-8901. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Foot-and-mouth disease (FMD) is a fast-spreading viral infection that can produce large and costly outbreaks in livestock populations. Transmission occurs at multiple spatial scales, as can the actions used to control outbreaks. The US cattle industry is spatially expansive, with heterogeneous distributions of animals and infrastructure. We have developed a model that incorporates the effects of scale for both disease transmission and control actions, applied here in simulating FMD outbreaks in US cattle. We simulated infection initiating in each of the 3049 counties in the contiguous US, 100 times per county. When initial infection was located in specific regions, large outbreaks were more likely to occur, driven by infrastructure and other demographic attributes such as premises clustering and number of cattle on premises. Sensitivity analyses suggest these attributes had more impact on outbreak metrics than the ranges of estimated disease parameter values. Additionally, although shipping accounted for a small percentage of overall transmission, areas receiving the most animal shipments tended to have other attributes that increase the probability of large outbreaks. The importance of including spatial and demographic heterogeneity in modelling outbreak trajectories and control actions is illustrated by specific regions consistently producing larger outbreaks than others. © 2019 The Author(s) Published by the Royal Society. All rights reserved.
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| 11. |
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| 12. |
- Bourguignon, J., et al.
(författare)
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Chiral ditopic receptors. Application to palladium-catalyzed allylic alkylation
- 2003
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Ingår i: Tetrahedron. - : Elsevier BV. - 0040-4020 .- 1464-5416. ; 59:48, s. 9583-9589
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Tidskriftsartikel (refereegranskat)abstract
- Chiral pyridinooxazoline, quinolinooxazoline, bis(oxazolino)pyridine (pybox), and bisoxazoline (box) derivatives containing crown ether residues were prepared. Some of the ligands were assessed in substrate binding studies and in palladium catalyzed allylic alkylations.
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| 13. |
- Chen, Jing, et al.
(författare)
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Dissecting maternal and fetal genetic effects underlying the associations between maternal phenotypes, birth outcomes, and adult phenotypes: A mendelian-randomization and haplotype-based genetic score analysis in 10,734 mother-infant pairs.
- 2020
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Ingår i: PLoS medicine. - : Public Library of Science (PLoS). - 1549-1676. ; 17:8
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Tidskriftsartikel (refereegranskat)abstract
- Many maternal traits are associated with a neonate's gestational duration, birth weight, and birth length. These birth outcomes are subsequently associated with late-onset health conditions. The causal mechanisms and the relative contributions of maternal and fetal genetic effects behind these observed associations are unresolved.Based on 10,734 mother-infant duos of European ancestry from the UK, Northern Europe, Australia, and North America, we constructed haplotype genetic scores using single-nucleotide polymorphisms (SNPs) known to be associated with adult height, body mass index (BMI), blood pressure (BP), fasting plasma glucose (FPG), and type 2 diabetes (T2D). Using these scores as genetic instruments, we estimated the maternal and fetal genetic effects underlying the observed associations between maternal phenotypes and pregnancy outcomes. We also used infant-specific birth weight genetic scores as instrument and examined the effects of fetal growth on pregnancy outcomes, maternal BP, and glucose levels during pregnancy. The maternal nontransmitted haplotype score for height was significantly associated with gestational duration (p = 2.2 × 10-4). Both maternal and paternal transmitted height haplotype scores were highly significantly associated with birth weight and length (p < 1 × 10-17). The maternal transmitted BMI scores were associated with birth weight with a significant maternal effect (p = 1.6 × 10-4). Both maternal and paternal transmitted BP scores were negatively associated with birth weight with a significant fetal effect (p = 9.4 × 10-3), whereas BP alleles were significantly associated with gestational duration and preterm birth through maternal effects (p = 3.3 × 10-2 and p = 4.5 × 10-3, respectively). The nontransmitted haplotype score for FPG was strongly associated with birth weight (p = 4.7 × 10-6); however, the glucose-increasing alleles in the fetus were associated with reduced birth weight through a fetal effect (p = 2.2 × 10-3). The haplotype scores for T2D were associated with birth weight in a similar way but with a weaker maternal effect (p = 6.4 × 10-3) and a stronger fetal effect (p = 1.3 × 10-5). The paternal transmitted birth weight score was significantly associated with reduced gestational duration (p = 1.8 × 10-4) and increased maternal systolic BP during pregnancy (p = 2.2 × 10-2). The major limitations of the study include missing and heterogenous phenotype data in some data sets and different instrumental strength of genetic scores for different phenotypic traits.We found that both maternal height and fetal growth are important factors in shaping the duration of gestation: genetically elevated maternal height is associated with longer gestational duration, whereas alleles that increase fetal growth are associated with shorter gestational duration. Fetal growth is influenced by both maternal and fetal effects and can reciprocally influence maternal phenotypes: taller maternal stature, higher maternal BMI, and higher maternal blood glucose are associated with larger birth size through maternal effects; in the fetus, the height- and metabolic-risk-increasing alleles are associated with increased and decreased birth size, respectively; alleles raising birth weight in the fetus are associated with shorter gestational duration and higher maternal BP. These maternal and fetal genetic effects may explain the observed associations between the studied maternal phenotypes and birth outcomes, as well as the life-course associations between these birth outcomes and adult phenotypes.
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| 14. |
- Clays, Els, et al.
(författare)
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Objectively measured occupational physical activities in blue collar jobs: do psychosocial resources matter?
- 2017
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Ingår i: European Journal of Preventive Cardiology. - 2047-4873 .- 2047-4881. ; 24:2S
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Occupational physical activity (OPA), and particularly static postures and physically exerting activities, is known to impact worker health and to increase the risk of cardiovascular disease, musculoskeletal problems, sickness absence and premature retirement. The exploration of structural preventive measures at the workplace against the adverse health effects of excessive OPA is needed. The psychosocial work environment is hypothesised to buffer the adverse effects of OPA, and as such psychosocial resources might directly influence the performance of OPA. However, this has not been previously investigated with detailed objective measurements. The aim of this study is to describe OPA within blue-collar workers, and to examine the role of psychosocial job resources in the performance of OPA.Methods: Results are based on a sample of 198 blue-collar workers from the NOMAD (New method for Objective Measurements of physical Activity in Daily living) study, recruited from seven workplaces in Denmark. The sample included 112 men (56.6%) and 86 women (43.4%); the mean age was 44.9 years (SD 9.9). Data were collected with two Actigraph devices placed on the thigh and trunk, during four consecutive days. The accelerometer data were processed and analysed using the Acti4 software, to determine working time spent standing, walking, on feet and in activity of moderate to vigorous intensity level (MVPA). The level of influence and social support at work were assessed by questionnaire, and measured with a four-item scale. Analysis of (co-)variance and (multiple) linear regression models were conducted. All analyses were stratified by gender predominance of occupation.Results: The different types of OPA significantly varied by particular job type. Within male predominant occupations, job type accounted for 50–70% of explained variance, depending on the type of OPA. Manufacturing workers showed the highest average proportions of working time standing (33%) and on feet (79%), while garbage collectors had the highest proportion of working time in MVPA (33%). Mobile plant operators and construction workers had the lowest average working time spent walking and in MVPA. Differences in OPA between job types in female predominant occupations were less pronounced, but healthcare workers and cleaners had higher average proportions of time spent walking and in MVPA compared to assembly workers. The addition of age and psychosocial resources to the models did not contribute to a larger explained variance in OPA and the relations with job type remained significant. Social support at work showed an independent positive relation with working on feet, and with standing in female predominant jobs only. Influence at work was not related to OPA.Conclusion: The positive relation of social support with working on feet and standing is likely to be explained by the nature of the work tasks, as jobs that require these activities probably comprise more close interactions and as such create more intensified levels of cooperation at the work floor. Overall, our hypothesis that psychosocial job resources would affect the performance of OPA within blue-collar workers was not confirmed. These findings suggest that the performance of OPA within blue-collarjobs – and particularly within male predominant occupations – is mostly affected by work organisational factors related to specific job type, and not by psychosocial job resources.
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| 15. |
- Coenen, Pieter, et al.
(författare)
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Differences in heart rate reserve of similar physical activities during work and in leisure time - A study among Danish blue-collar workers
- 2018
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Ingår i: Physiology and Behavior. - : Elsevier BV. - 0031-9384 .- 1873-507X. ; 185, s. 45-51
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies suggest that while leisure-time physical activity (LTPA) promotes general health, engaging in occupational physical activity (OPA) may have negative health consequences. It has been hypothesized that the different health effects from OPA and LTPA can be explained by differences in physical activity (PA) intensity in these two domains. To assess the intensity of OPA and LTPA, we aimed to study the percentage heart rate reserve (%HRR) during similar types of OPA and LTPA during workdays. Data from the NOMAD study on Danish blue-collar workers (n=124) with objective measurements of PA (using accelerometers) and heart rate (using heart rate monitors) for 4 workdays were analysed. Activities of sitting, standing, moving, walking, and stair climbing were identified and %HRR in each of these activities was determined for work and leisure. %HRR was significantly higher during OPA than LTPA. These differences were more pronounced in men than in women. Although not statistically significant in the fully adjusted model, we found indications that these differences were more pronounced in those with low compared to high fitness. To our knowledge, this is the first study with objective measurements showing that %HRR is higher during the same gross-body postural activities when performed at work compared to leisure-time during workdays. This elevated intensity may help explaining the negative health consequences of engagement in high levels of OPA. Future guidelines should distinguish OPA from LTPA, possibly by advising workers to remain active during their leisure time, in particular when they are highly active at work.
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| 16. |
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| 17. |
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| 18. |
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| 19. |
- Fetissov, SO, et al.
(författare)
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Autoantibodies against alpha -MSH, ACTH, and LHRH in anorexia and bulimia nervosa patients
- 2002
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 99:26, s. 17155-17160
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Tidskriftsartikel (refereegranskat)abstract
- The hypothalamic arcuate nucleus is involved in the control of energy intake and expenditure and may participate in the pathogenesis of eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). Two systems are of particular interest in this respect, synthesizing α-melanocyte-stimulating hormone (α-MSH) and synthesizing neuropeptide Y, respectively. We report here that 42 of 57 (74%) AN and/or BN patients studied had in their plasma Abs that bind to melanotropes and/or corticotropes in the rat pituitary. Among these sera, 8 were found to bind selectively to α-MSH-positive neurons and their hypothalamic and extrahypothalamic projections as revealed with immunostaining on rat brain sections. Adsorption of these sera with α-MSH peptide abolished this immunostaining. In the pituitary, the immunostaining was blocked by adsorption with α-MSH or adrenocorticotropic hormone. Additionally, 3 AN/BN sera bound to luteinizing hormone-releasing hormone (LHRH)-positive terminals in the rat median eminence, but only 2 of them were adsorbed with LHRH. In the control subjects, 2 of 13 sera (16%) displayed similar to AN/BN staining. These data provide evidence that a significant subpopulation of AN/BN patients have autoantibodies that bind to α-MSH or adrenocorticotropic hormone, a finding pointing also to involvement of the stress axis. It remains to be established whether these Abs interfere with normal signal transduction in the brain melanocortin circuitry/LHRH system and/or in other central and peripheral sites relevant to food intake regulation, to what extent such effects are related to and/or could be involved in the pathophysiology or clinical presentation of AN/BN, and to what extent increased stress is an important factor for production of these autoantibodies.
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| 20. |
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| 21. |
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| 22. |
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| 23. |
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| 24. |
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| 25. |
- Gilbertson, Kendra, et al.
(författare)
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The Importance of Livestock Demography and Infrastructure in Driving Foot and Mouth Disease Dynamics
- 2022
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Ingår i: Life. - : MDPI. - 2075-1729. ; 12:10
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Tidskriftsartikel (refereegranskat)abstract
- Transboundary animal diseases, such as foot and mouth disease (FMD) pose a significant and ongoing threat to global food security. Such diseases can produce large, spatially complex outbreaks. Mathematical models are often used to understand the spatio-temporal dynamics and create response plans for possible disease introductions. Model assumptions regarding transmission behavior of premises and movement patterns of livestock directly impact our understanding of the ecological drivers of outbreaks and how to best control them. Here, we investigate the impact that these assumptions have on model predictions of FMD outbreaks in the U.S. using models of livestock shipment networks and disease spread. We explore the impact of changing assumptions about premises transmission behavior, both by including within-herd dynamics, and by accounting for premises type and increasing the accuracy of shipment predictions. We find that the impact these assumptions have on outbreak predictions is less than the impact of the underlying livestock demography, but that they are important for investigating some response objectives, such as the impact on trade. These results suggest that demography is a key ecological driver of outbreaks and is critical for making robust predictions but that understanding management objectives is also important when making choices about model assumptions.
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| 26. |
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| 27. |
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| 32. |
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| 33. |
- Huusko, Johanna M, et al.
(författare)
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Integrative genetic, genomic and transcriptomic analysis of heat shock protein and nuclear hormone receptor gene associations with spontaneous preterm birth.
- 2021
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Heat shock proteins are involved in the response to stress including activation of the immune response. Elevated circulating heat shock proteins are associated with spontaneous preterm birth (SPTB). Intracellular heat shock proteins act as multifunctional molecular chaperones that regulate activity of nuclear hormone receptors. Since SPTB has a significant genetic predisposition, our objective was to identify genetic and transcriptomic evidence of heat shock proteins and nuclear hormone receptors that may affect risk for SPTB. We investigated all 97 genes encoding members of the heat shock protein families and all 49 genes encoding nuclear hormone receptors for their potential role in SPTB susceptibility. We used multiple genetic and genomic datasets including genome-wide association studies (GWASs), whole-exome sequencing (WES), and placental transcriptomics to identify SPTB predisposing factors from the mother, infant, and placenta. There were multiple associations of heat shock protein and nuclear hormone receptor genes with SPTB. Several orthogonal datasets supported roles for SEC63, HSPA1L, SACS, RORA, and AR in susceptibility to SPTB. We propose that suppression of specific heat shock proteins promotes maintenance of pregnancy, whereas activation of specific heat shock protein mediated signaling may disturb maternal-fetal tolerance and promote labor.
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| 34. |
- Huusko, Johanna M, et al.
(författare)
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Whole exome sequencing reveals HSPA1L as a genetic risk factor for spontaneous preterm birth.
- 2018
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 14:7
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Tidskriftsartikel (refereegranskat)abstract
- Preterm birth is a leading cause of morbidity and mortality in infants. Genetic and environmental factors play a role in the susceptibility to preterm birth, but despite many investigations, the genetic basis for preterm birth remain largely unknown. Our objective was to identify rare, possibly damaging, nucleotide variants in mothers from families with recurrent spontaneous preterm births (SPTB). DNA samples from 17 Finnish mothers who delivered at least one infant preterm were subjected to whole exome sequencing. All mothers were of northern Finnish origin and were from seven multiplex families. Additional replication samples of European origin consisted of 93 Danish sister pairs (and two sister triads), all with a history of a preterm delivery. Rare exonic variants (frequency <1%) were analyzed to identify genes and pathways likely to affect SPTB susceptibility. We identified rare, possibly damaging, variants in genes that were common to multiple affected individuals. The glucocorticoid receptor signaling pathway was the most significant (p<1.7e-8) with genes containing these variants in a subgroup of ten Finnish mothers, each having had 2-4 SPTBs. This pathway was replicated among the Danish sister pairs. A gene in this pathway, heat shock protein family A (Hsp70) member 1 like (HSPA1L), contains two likely damaging missense alleles that were found in four different Finnish families. One of the variants (rs34620296) had a higher frequency in cases compared to controls (0.0025 vs. 0.0010, p = 0.002) in a large preterm birth genome-wide association study (GWAS) consisting of mothers of general European ancestry. Sister pairs in replication samples also shared rare, likely damaging HSPA1L variants. Furthermore, in silico analysis predicted an additional phosphorylation site generated by rs34620296 that could potentially affect chaperone activity or HSPA1L protein stability. Finally, in vitro functional experiment showed a link between HSPA1L activity and decidualization. In conclusion, rare, likely damaging, variants in HSPA1L were observed in multiple families with recurrent SPTB.
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| 35. |
- Larisch, Lisa-Marie, et al.
(författare)
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Effects of two randomized and controlled multi-component interventions focusing on 24-hour movement behavior among office workers: A compositional data analysis
- 2021
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Intervention studies aiming at changing movement behavior have usually not accounted for the compositional nature of time-use data. Compositional data analysis (CoDA) has been sug-gested as a useful strategy for analyzing such data. The aim of this study was to examine the effects of two multi-component interventions on 24-h movement behavior (using CoDA) and on cardi-orespiratory fitness among office workers; one focusing on reducing sedentariness and the other on increasing physical activity. Office workers (n = 263) were cluster randomized into one of two 6-month intervention groups, or a control group. Time spent in sedentary behavior, light-intensity, moderate and vigorous physical activity, and time in bed were assessed using accelerometers and diaries, both for 24 h in total, and for work and leisure time separately. Cardiorespiratory fitness was estimated using a sub-maximal cycle ergometer test. Intervention effects were analyzed using linear mixed models. No intervention effects were found, either for 24-h behaviors in total, or for work and leisure time behaviors separately. Cardiorespiratory fitness did not change significantly. Despite a thorough analysis of 24-h behaviors using CoDA, no intervention effects were found, nei-ther for behaviors in total, nor for work and leisure time behaviors separately. Cardiorespiratory fitness did not change significantly. Although the design of the multi-component interventions was based on theoretical frameworks, and included cognitive behavioral therapy counselling, which has been proven effective in other populations, issues related to implementation of and compliance with some intervention components may have led to the observed lack of intervention effect.
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| 36. |
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| 37. |
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| 38. |
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| 39. |
- Longato-Stadler, E, et al.
(författare)
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Personality traits and platelet monoamine oxidase activity in a Swedish male criminal population
- 2002
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Ingår i: Neuropsychobiology. - : S. Karger AG. - 0302-282X .- 1423-0224. ; 46:4, s. 202-208
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> A Swedish male criminal population was grouped into personality disorder subgroups and investigated with regard to personality traits and platelet monoamine oxidase (MAO) activity. The main aim of the study was to examine the possibility of a risk factor combination by having low platelet MAO activity as well as belonging to a certain diagnostic DSM-IV axis I (drug abuse in the present series) and/or II subgroup. <i>Methods:</i> Personality disorders were grouped into clusters according to the cluster system used in DSM-IV axis II. The prisoners were grouped into five subgroups and each subject completed the Karolinska Scales of Personality self-report questionnaire. The comparison group for the personality data comprised 51 non-criminal males from a longitudinal Swedish project. Platelet MAO activity was assessed for the criminals as well as for a control group including 60 non-criminal healthy male Caucasians. For testing the existence of syndromes, a configuration frequency analysis (CFA) was used. <i>Results:</i> The results showed low scores on the socialisation and high scores on the sensation seeking-related traits impulsiveness and monotony avoidance, and the somatic anxiety-related muscular tension in the criminals with any DSM-IV mental disorder, however most markedly in cluster AB and cluster B subjects. In addition, cluster AB subjects had significantly lower platelet MAO activity than controls. Two significant ‘types’ were found among the criminals: one was characterised by low platelet MAO activity, cluster B personality diagnosis as well as drug abuse disorder diagnosis; and the other by a pattern of normal platelet MAO activity, no cluster B personality disorder and no drug abuse disorder diagnosis. <i>Conclusion:</i> The aggregation of certain risk factors in the same individual has been shown to contribute to the development of criminal behaviour.
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| 40. |
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| 41. |
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| 42. |
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| 43. |
- Oreland, Lars, et al.
(författare)
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Environment and the serotonergic system
- 2010
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Ingår i: European psychiatry. - : Cambridge University Press (CUP). - 0924-9338 .- 1778-3585. ; 25:5, s. 304-306
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Tidskriftsartikel (refereegranskat)abstract
- In summary, genetics, as well as foetal and early life environmental factors shape the size or capacity of our monoamine systems, of which the serotonergic one might play a leading role. Those constitutional properties then form the biological basis for personality traits, such as impulsiveness and "sensation seeking", which interact with psychosocial settings and life events to form a pattern of reactivity to a current life event or psychosocial situation, shown as a high or low order of magnitude of gene-environment interaction. In the present paper emphasis is put on the role of genotypes of the serotonin transporter, of monoamine oxidases A and B, and of platelet monoamine oxidase B activity, which all have been shown to be of importance for behaviour and with obvious effects of interactions with environment. Under unfortunate circumstances constitutional properties might be strong enough to result in vulnerability for suicide, even with a modest influence of environment.
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| 44. |
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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. |
- Pasanen, Anu, et al.
(författare)
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Meta-analysis of genome-wide association studies of gestational duration and spontaneous preterm birth identifies new maternal risk loci.
- 2023
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Ingår i: PLoS genetics. - 1553-7404. ; 19:10
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Tidskriftsartikel (refereegranskat)abstract
- Preterm birth (<37 weeks of gestation) is a major cause of neonatal death and morbidity. Up to 40% of the variation in timing of birth results from genetic factors, mostly due to the maternal genome.We conducted a genome-wide meta-analysis of gestational duration and spontaneous preterm birth in 68,732 and 98,370 European mothers, respectively.The meta-analysis detected 15 loci associated with gestational duration, and four loci associated with preterm birth. Seven of the associated loci were novel. The loci mapped to several biologically plausible genes, for example HAND2 whose expression was previously shown to decrease during gestation, associated with gestational duration, and GC (Vitamin D-binding protein), associated with preterm birth. Downstream in silico-analysis suggested regulatory roles as underlying mechanisms for the associated loci. LD score regression found birth weight measures as the most strongly correlated traits, highlighting the unique nature of spontaneous preterm birth phenotype. Tissue expression and colocalization analysis revealed reproductive tissues and immune cell types as the most relevant sites of action.We report novel genetic risk loci that associate with preterm birth or gestational duration, and reproduce findings from previous genome-wide association studies. Altogether, our findings provide new insight into the genetic background of preterm birth. Better characterization of the causal genetic mechanisms will be important to public health as it could suggest new strategies to treat and prevent preterm birth.
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| 50. |
- Plunkett, Jevon, et al.
(författare)
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An Evolutionary Genomic Approach to Identify Genes Involved in Human Birth Timing
- 2011
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- Coordination of fetal maturation with birth timing is essential for mammalian reproduction. In humans, preterm birth is a disorder of profound global health significance. The signals initiating parturition in humans have remained elusive, due to divergence in physiological mechanisms between humans and model organisms typically studied. Because of relatively large human head size and narrow birth canal cross-sectional area compared to other primates, we hypothesized that genes involved in parturition would display accelerated evolution along the human and/or higher primate phylogenetic lineages to decrease the length of gestation and promote delivery of a smaller fetus that transits the birth canal more readily. Further, we tested whether current variation in such accelerated genes contributes to preterm birth risk. Evidence from allometric scaling of gestational age suggests human gestation has been shortened relative to other primates. Consistent with our hypothesis, many genes involved in reproduction show human acceleration in their coding or adjacent noncoding regions. We screened.8,400 SNPs in 150 human accelerated genes in 165 Finnish preterm and 163 control mothers for association with preterm birth. In this cohort, the most significant association was in FSHR, and 8 of the 10 most significant SNPs were in this gene. Further evidence for association of a linkage disequilibrium block of SNPs in FSHR, rs11686474, rs11680730, rs12473870, and rs1247381 was found in African Americans. By considering human acceleration, we identified a novel gene that may be associated with preterm birth, FSHR. We anticipate other human accelerated genes will similarly be associated with preterm birth risk and elucidate essential pathways for human parturition.
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