| 1. |
- Sliz, E., et al.
(författare)
-
Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
|
|
| 2. |
|
|
| 3. |
- Guintivano, Jerry, et al.
(författare)
-
Meta-Analyses of Genome-Wide Association Studies for Postpartum Depression
- 2023
-
Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 180:12, s. 884-895
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Postpartum depression (PPD) is a common subtype of major depressive disorder (MDD) that is more heritable, yet is understudied in psychiatric genetics. The authors conducted meta-analyses of genome-wide association studies (GWASs) to investigate the genetic architecture of PPD.METHOD: Meta-analyses were conducted on 18 cohorts of European ancestry (17,339 PPD cases and 53,426 controls), one cohort of East Asian ancestry (975 cases and 3,780 controls), and one cohort of African ancestry (456 cases and 1,255 controls), totaling 18,770 PPD cases and 58,461 controls. Post-GWAS analyses included 1) single-nucleotide polymorphism (SNP)-based heritability ([Formula: see text]), 2) genetic correlations between PPD and other phenotypes, and 3) enrichment of the PPD GWAS findings in 27 human tissues and 265 cell types from the mouse central and peripheral nervous system.RESULTS: No SNP achieved genome-wide significance in the European or the trans-ancestry meta-analyses. The [Formula: see text] of PPD was 0.14 (SE=0.02). Significant genetic correlations were estimated for PPD with MDD, bipolar disorder, anxiety disorders, posttraumatic stress disorder, insomnia, age at menarche, and polycystic ovary syndrome. Cell-type enrichment analyses implicate inhibitory neurons in the thalamus and cholinergic neurons within septal nuclei of the hypothalamus, a pattern that differs from MDD.CONCLUSIONS: While more samples are needed to reach genome-wide levels of significance, the results presented confirm PPD as a polygenic and heritable phenotype. There is also evidence that despite a high correlation with MDD, PPD may have unique genetic components. Cell enrichment results suggest GABAergic neurons, which converge on a common mechanism with the only medication approved by the U.S. Food and Drug Administration for PPD (brexanolone).
|
|
| 4. |
- Aberg, N, et al.
(författare)
-
Increase of asthma, allergic rhinitis and eczema in Swedish schoolchildren between 1979 and 1991.
- 1995
-
Ingår i: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. - : Wiley. - 0954-7894. ; 25:9, s. 815-9
-
Tidskriftsartikel (refereegranskat)abstract
- A previous study has shown a twofold increase in prevalence of asthma and allergic rhinitis (AR) in Swedish recruits during the 1970s. The increase was higher in more northerly colder regions.To follow up the previously found trend to increasing prevalences with time as well as the climatic variations within the country.The prevalences of asthma, allergic rhinitis and eczema were assessed using two questionnaire studies, 12 years apart (1979 and 1991) with identical questions about the diseases. The study comprised representative samples of children from the Göteborg area on the south-western coast (in 1979: 7-year-olds, n = 4255, in 1991: 7-year-olds, n = 1649) and in Kiruna, a mining town in the northernmost inland mountains (in 1979: 7-year-olds, n = 427, in 1991: 7-9-year-olds, n = 832). In 1991 there was also a personal interview and a skin-prick test (SPT) on subsamples.The prevalence of all these diseases present over the last year had roughly doubled over the 12-year period. On both occasions, most symptoms were more prevalent in the northern area. In 1991, the prevalence of one or more symptoms in Göteborg was 23.8% and 32.5% and in Kiruna 29.9% and 44.8% in the questionnaire and the interview, respectively.Asthma, AR and eczema increase continuously in prevalence in Sweden and the climatic distribution of the prevalences suggests possible major risk factors to be found in a closed indoor climate.
|
|
| 5. |
- Aberg, N, et al.
(författare)
-
Prevalence of allergic diseases in schoolchildren in relation to family history, upper respiratory infections, and residential characteristics.
- 1996
-
Ingår i: Allergy. - : Wiley. - 0105-4538 .- 1398-9995. ; 51:4, s. 232-7
-
Tidskriftsartikel (refereegranskat)abstract
- The prevalences of asthma, allergic rhinitis (AR), and eczema were analyzed in relation to retrospective risk factors from birth in a questionnaire study of schoolchildren in two areas covering the whole climatic span of Sweden: the Göteborg area on the southwestern coast (7-year-olds, n = 1649) and Kiruna, a mining town in the northernmost inland mountains (7-9-year-olds, n = 832). The strongest background factor, a family history of the diseases, was more common in children with another strong risk factor, particularly for asthma: high frequency of upper respiratory tract infection (URTI). Other significant risk factors related to high indoor humidity caused an increased prevalence of both allergic diseases and URTI. Active mechanical ventilation of the homes caused a slight reduction of the prevalence of allergic diseases, and repainting or new wallpaper in the bedroom of the child after birth caused a moderately increased risk of allergic disease. This study illustrates the interaction between genetic and environmental risk factors with special emphasis on factors related to an unventilated indoor climate, which may have substantially contributed to the current increase of the diseases in the country.
|
|
| 6. |
- Hesselmar, Bill, 1955, et al.
(författare)
-
Asthma in children: prevalence, treatment, and sensitization.
- 2000
-
Ingår i: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. - : Wiley. - 0905-6157. ; 11:2, s. 74-9
-
Tidskriftsartikel (refereegranskat)abstract
- This study compares the prevalence of asthma and sensitization in children from two Swedish regions with different climates: Göteborg on the southwest coast and Kiruna in the northern inland, north of the Arctic Circle. The 412 children of a population-based sample, 203 in Göteborg and 209 in Kiruna, were investigated at age 7-8 and 12-13 years. Questionnaire reports and interviews were obtained from all children at 7-8 years of age, and 192 children were skin-prick tested for common aeroallergens in Göteborg and 205 in Kiruna. At the follow-up, 5 years later, almost all the children were re-investigated. The prevalence of asthma, wheeze, and sensitization had increased with increasing age during the follow-up period. The questionnaire reports revealed that the prevalence of asthma was 8.5% at 12-13 years of age. All children who in the questionnaire reported current asthma, were using asthma medication. The interviews indicated that the prevalence of a clinically significant asthma might be even higher, reaching approximately 12%. Asthma and wheeze were as common in Göteborg as in Kiruna despite large differences in prevalence of sensitization. Sensitization, and especially sensitization to animals, was far more common in Kiruna than in Göteborg. This study shows that asthma and wheeze are increasingly prevalent even in school age children and that sensitization does not necessarily reflect the prevalence of asthma in a population.
|
|
| 7. |
- Hesselmar, Bill, 1955, et al.
(författare)
-
Does early exposure to cat or dog protect against later allergy development?
- 1999
-
Ingår i: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. - : Wiley. - 0954-7894. ; 29:5, s. 611-7
-
Tidskriftsartikel (refereegranskat)abstract
- It is unknown which factors in modern western society that have caused the current increase in prevalence of allergic diseases. Improved hygiene, smaller families, altered exposure to allergens have been suggested.To assess the relationship between exposure to pets in early life, family size, allergic manifestations and allergic sensitization at 7-9 and 12-13 years of age.The prevalence of allergic diseases and various background factors were assessed in 1991 and 1996 by questionnaire studies. In 1991, the study comprised representative samples of children from the Göteborg area on the Swedish west coast (7 years old, n = 1649) and the inland town Kiruna in northern Sweden (7-9 years old, n = 832). In 1992, a validation interview and skin prick test (SPT) were performed in a stratified sub-sample of 412 children. In 1996, this subgroup was followed up with identical questions about clinical symptoms as in 1991, detailed questions about early pet exposure were added and SPT performed.Children exposed to pets during the first year of life had a lower frequency of allergic rhinitis at 7-9 years of age and of asthma at 12-13 years. Children exposed to cat during the first year of life were less often SPT positive to cat at 12-13 years. The results were similar when those children were excluded, whose parents had actively decided against pet keeping during infancy because of allergy in the family. There was a negative correlation between the number of siblings and development of asthma and allergic rhinitis.Pet exposure during the first year of life and increasing number of siblings were both associated with a lower prevalence of allergic rhinitis and asthma in school children.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
- Hesselmar, Bill, 1955, et al.
(författare)
-
Born small for gestational age: relation to future allergy and asthma
- 2002
-
Ingår i: Acta Paediatrica. - 0803-5253. ; 91:9, s. 992-4
-
Tidskriftsartikel (refereegranskat)abstract
- AIM: To evaluate whether intrauterine growth retardation (IUGR) protects against the development of allergy. METHODS: A case-control study of 1515 subjects (15-25 y), of whom 430 were cases (birthweight/length below -2 SD for gestational age). Birth data were from the national birth register. The frequencies of allergic diseases were evaluated by questionnaire. RESULTS: For the 950 who replied, the frequencies of allergic diseases were similar in cases and controls. CONCLUSION: IUGR does not protect against the development of allergy.
|
|
| 17. |
- Hjern, A, et al.
(författare)
-
Migration and atopic disorder in Swedish conscripts
- 1999
-
Ingår i: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. - : Wiley. - 0905-6157. ; 10:3, s. 209-215
-
Tidskriftsartikel (refereegranskat)
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
- Lundqvist, N., et al.
(författare)
-
Effects of substrate bias and temperature during titanium sputter-deposition on the phase formation in TiSi2
- 2002
-
Ingår i: Microelectronic Engineering. - 0167-9317 .- 1873-5568. ; 60:02-jan, s. 211-220
-
Tidskriftsartikel (refereegranskat)abstract
- The formation of titanium disilicide (TiSi2,) from Ti deposited using ionized metal plasma under different deposition conditions has been investigated. It is shown that deposition at elevated substrate temperature (450degreesC) enhances the formation of the low-resistivity C54 TiSi2, especially in patterned narrow lines. Grain-boundary footprint pictures obtained by atomic force microscopy indicate a larger grain-size distribution for the films deposited at higher substrate temperature. Deposition under substrate bias resulted in reduced contact resistivity. However, the use of substrate bias results in increased probability of bridging of silicide over the isolating spacers.
|
|
| 21. |
- Walser, Marion, 1961, et al.
(författare)
-
Growth Hormone and Neuronal Hemoglobin in the Brain-Roles in Neuroprotection and Neurodegenerative Diseases
- 2021
-
Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- In recent years, evidence for hemoglobin (Hb) synthesis in both animal and human brains has been accumulating. While circulating Hb originating from cerebral hemorrhage or other conditions is toxic, there is also substantial production of neuronal Hb, which is influenced by conditions such as ischemia and regulated by growth hormone (GH), insulin-like growth factor-I (IGF-I), and other growth factors. In this review, we discuss the possible functions of circulating and brain Hb, mainly the neuronal form, with respect to the neuroprotective activities of GH and IGF-I against ischemia and neurodegenerative diseases. The molecular pathways that link Hb to the GH/IGF-I system are also reviewed, although the limited number of reports on this topic suggests a need for further studies. In summary, GH and/or IGF-I appear to be significant determinants of systemic and local brain Hb concentrations through mediating responses to oxygen and metabolic demand, as part of the neuroprotective effects exerted by GH and IGF-I. The nature and quantity of the latter deserve further exploration in specific experiments.
|
|
| 22. |
- Walser, M., et al.
(författare)
-
Local overexpression of GH and GH/IGF1 effects in the adult mouse hippocampus
- 2012
-
Ingår i: Journal of Endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 215:2, s. 257-268
-
Tidskriftsartikel (refereegranskat)abstract
- GH therapy improves hippocampal functions mainly via circulating IGF1. However, the roles of local GH and IGF1 expression are not well understood. We investigated whether transgenic (TG) overexpression in the adult brain of bovine GH (bGH) under the control of the glial fibrillary acidic protein (GFAP) promoter affected cellular proliferation and the expression of transcripts known to be induced by systemic GH in the hippocampus. Cellular proliferation was examined by 5-bromo-2'-deoxyuridine immunohistochemistry. Quantitative PCR and western blots were performed. Although robustly expressed, bGH-Tg did not increase either cell proliferation or survival. However, bGH-Tg modestly increased Igf1 and Gfap mRNAs, whereas other GH-associated transcripts were unaffected, i.e. the GH receptor (Ghr), IGF1 receptor (Igf1r), 2',3'-cyclic nucleotide 3'-phosphodiesterase (Cnp), ionotropic glutamate receptor 2a (Nr2a (Grin2a)), opioid receptor delta (Dor), synapse-associated protein 90/postsynaptic density-95-associated protein (Sapap2 (Dlgap2)), haemoglobin beta (Hbb) and glutamine synthetase (Gs (Glul)). However, IGF1R was correlated with the expression of Dor, Nr2a, Sapap2, Gs and Gfap. In summary, although local bGH expression was robust, it activated local IGF1 very modestly, which is probably the reason for the low response of previous GH-associated response parameters. This would, in turn, indicate that hippocampal GH is less important than endocrine GH. However, as most transcripts were correlated with the expression of IGF1R, there is still a possibility for endogenous circulating or local GH to act via IGF1R signalling. Possible reasons for the relative bio-inactivity of bGH include the bell-shaped dose-response curve and cell-specific expression of bGH. Journal of Endocrinology (2012) 215, 257-268
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
- Åberg, N David, 1970, et al.
(författare)
-
Insulin-like growth factor-I increases astrocyte intercellular gap junctional communication and connexin43 expression in vitro.
- 2003
-
Ingår i: Journal of neuroscience research. - : Wiley. - 0360-4012. ; 74:1, s. 12-22
-
Tidskriftsartikel (refereegranskat)abstract
- Connexin43 (cx43) forms gap junctions in astrocytes, and these gap junctions mediate intercellular communication by providing transport of low-molecular-weight metabolites and ions. We have recently shown that systemic growth hormone increases cx43 in the brain. One possibility was that local brain insulin-like growth factor-I (IGF-I) could mediate the effect by acting directly on astrocytes. In the present study, we examined the effects of direct application of recombinant human IGF-I (rhIGF-I) on astrocytes in primary culture concerning cx43 protein expression and gap junctional communication (GJC). After 24 hr of stimulation with rhIGF-I under serum-free conditions, the GJC and cx43 protein were analyzed. Administration of 30 ng/ml rhIGF-I increased the GJC and the abundance of cx43 protein. Cell proliferation of the astrocytes was not significantly increased by rhIGF-I at this concentration. However, a higher concentration of rhIGF-I (150 ng/ml) had no effect on GJC/cx43 but increased cell proliferation. Because of the important modulatory role of IGF binding proteins (IGFBPs) on IGF-I action, we analyzed IGFBPs in conditioned media. In cultures with a low abundance of IGFBPs (especially IGFBP-2), the GJC response to 30 ng/ml rhIGF-I was 81%, compared with the average of 25%. Finally, as a control, insulin was given in equimolar concentrations. However, GJC was not affected, which suggests that rhIGF-I acted via IGF-I receptors. In summary, the data show that rhIGF-I may increase GJC/cx43, whereas a higher concentration of rhIGF-I--at which stimulation of proliferation occurred--did not affect GJC/cx43. Furthermore, IGFBP-2 appeared to modulate the action of rhIGF-I on GJC in astrocytes by a paracrine mechanism.
|
|
