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| 2. |
- Mullins, N., et al.
(författare)
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Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology
- 2021
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 53, s. 817-829
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.
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- Jonsson, Lina, 1982, et al.
(författare)
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Characterisation of age and polarity at onset in bipolar disorder
- 2021
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Ingår i: British Journal of Psychiatry. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 219:6, s. 659-669
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Tidskriftsartikel (refereegranskat)abstract
- Background Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools. Aims To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics. Method Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts. Results Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (beta = -0.34 years, s.e. = 0.08), major depression (beta = -0.34 years, s.e. = 0.08), schizophrenia (beta = -0.39 years, s.e. = 0.08), and educational attainment (beta = -0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO. Conclusions AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
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| 4. |
- Abdoullaye, Doukary, et al.
(författare)
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Permanent genetic resources added to molecular ecology resources database 1 August 2009 - 30 September 2009
- 2010
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Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:1, s. 232-236
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Tidskriftsartikel (refereegranskat)abstract
- This article documents the addition of 238 microsatellite marker loci and 72 pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Adelges tsugae, Artemisia tridentata, Astroides calycularis, Azorella selago, Botryllus schlosseri, Botrylloides violaceus, Cardiocrinum cordatum var. glehnii, Campylopterus curvipennis, Colocasia esculenta, Cynomys ludovicianus, Cynomys leucurus, Cynomys gunnisoni, Epinephelus coioides, Eunicella singularis, Gammarus pulex, Homoeosoma nebulella, Hyla squirella, Lateolabrax japonicus, Mastomys erythroleucus, Pararge aegeria, Pardosa sierra, Phoenicopterus ruber ruber and Silene latifolia. These loci were cross-tested on the following species: Adelges abietis, Adelges cooleyi, Adelges piceae, Pineus pini, Pineus strobi, Tubastrea micrantha, three other Tubastrea species, Botrylloides fuscus, Botrylloides simodensis, Campylopterus hemileucurus, Campylopterus rufus, Campylopterus largipennis, Campylopterus villaviscensio, Phaethornis longuemareus, Florisuga mellivora, Lampornis amethystinus, Amazilia cyanocephala, Archilochus colubris, Epinephelus lanceolatus, Epinephelus fuscoguttatus, Symbiodinium temperate-A clade, Gammarus fossarum, Gammarus roeselii, Dikerogammarus villosus and Limnomysis benedeni. This article also documents the addition of 72 sequencing primer pairs and 52 allele specific primers for Neophocaena phocaenoides.
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- Breugom, A. J., et al.
(författare)
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Adjuvant chemotherapy and relative survival of patients with stage II colon cancer - A EURECCA international comparison between the Netherlands, Denmark, Sweden, England, Ireland, Belgium, and Lithuania
- 2016
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 63, s. 110-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of the present EURECCA international comparison is to compare adjuvant chemotherapy and relative survival of patients with stage II colon cancer between European countries.Methods: Population-based national cohort data (2004-2009) from the Netherlands (NL), Denmark (DK), Sweden (SE), England (ENG), Ireland (IE), and Belgium (BE) were obtained, as well as single-centre data from Lithuania. All surgically treated patients with stage II colon cancer were included. The proportion of patients receiving adjuvant chemotherapy was calculated and compared between countries. Besides, relative survival was calculated and compared between countries.Results: Overall, 59,154 patients were included. The proportion of patients receiving adjuvant chemotherapy ranged from 7.1% to 29.0% (p < 0.001). Compared with NL, a better adjusted relative survival was observed in SE (stage II: relative excess risks (RER) 0.53, 95% confidence interval (CI) 0.44-0.64; p < 0.001), and BE (stage II: RER 0.84, 95% CI 0.76-0.92; p < 0.001), and in IE for patients with stage IIA disease (RER 0.80, 95% CI 0.65-0.98; p = 0.03).Conclusion: The proportion of patients with stage II colon cancer receiving adjuvant chemotherapy varied largely between seven European countries. No clear linear pattern between adjuvant chemotherapy and adjusted relative survival was observed. Compared with NL, SE and BE showed an improved adjusted relative survival for stage II disease, and IE for patients with stage IIA disease only. Further research into selection criteria for adjuvant chemotherapy could eventually lead to individually tailored, optimal treatment of patients with stage II colon cancer.
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- Breugom, A. J., et al.
(författare)
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Oncologic treatment strategies and relative survival of patients with stage I-III rectal cancer - A EURECCA international comparison between the Netherlands, Belgium, Denmark, Sweden, England, Ireland, Spain, and Lithuania
- 2018
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Ingår i: European Journal of Surgical Oncology. - : Elsevier. - 0748-7983 .- 1532-2157. ; 44:9, s. 1338-1343
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The aim of this EURECCA international comparison is to compare oncologic treatment strategies and relative survival of patients with stage I-III rectal cancer between European countries.Material and methods: Population-based national cohort data from the Netherlands (NL), Belgium (BE), Denmark (DK), Sweden (SE), England (ENG), Ireland (IE), Spain (ES), and single-centre data from Lithuania (LT) were obtained. All operated patients with (y)pTNM stage I-III rectal cancer diagnosed between 2004 and 2009 were included. Oncologic treatment strategies and relative survival were calculated and compared between neighbouring countries.Results: We included 57,120 patients. Treatment strategies differed between NL and BE (p < 0.001), DK and SE (p < 0.001), and ENG and IE (p < 0.001). More preoperative radiotherapy as single treatment before surgery was administered in NL compared with BE (59.7% vs. 13.1%), in SE compared with DK (55.1% vs. 10.4%), and in ENG compared with IE (15.2% vs. 9.6%). Less postoperative chemotherapy was given in NL (9.6% vs. 39.1%), in SE (7.9% vs. 14.1%), and in IE (12.6% vs. 18.5%) compared with their neighbouring country. In ES, 55.1% of patients received preoperative chemoradiation and 62.3% post-operative chemotherapy. There were no significant differences in relative survival between neighbouring countries.Conclusion: Large differences in oncologic treatment strategies for patients with (y)pTNM I-III rectal cancer were observed across European countries. No clear relation between oncologic treatment strategies and relative survival was observed. Further research into selection criteria for specific treatments could eventually lead to individualised and optimal treatment for patients with non-metastasised rectal cancer.
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| 10. |
- Wang, Xin, et al.
(författare)
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Global burden of respiratory infections associated with seasonal influenza in children under 5 years in 2018 : a systematic review and modelling study
- 2020
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Ingår i: The Lancet Global Health. - : Elsevier. - 2214-109X. ; 8:4, s. E497-E510
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Forskningsöversikt (refereegranskat)abstract
- Background: Seasonal influenza virus is a common cause of acute lower respiratory infection (ALRI) in ung children. In 2008, we estimated that 20 million influenza-virus-associated ALRI and 1 million fluenza-virus-associated severe ALRI occurred in children under 5 years globally. Despite this bstantial burden, only a few low-income and middle-income countries have adopted routine influenza ccination policies for children and, where present, these have achieved only low or unknown levels of ccine uptake. Moreover, the influenza burden might have changed due to the emergence and rculation of influenza A/H1N1pdm09. We aimed to incorporate new data to update estimates of the obal number of cases, hospital admissions, and mortality from influenza-virus-associated respiratory fections in children under 5 years in 2018.Methods: We estimated the regional and global burden of influenza-associated respiratory infections in ildren under 5 years from a systematic review of 100 studies published between Jan 1, 1995, and Dec , 2018, and a further 57 high-quality unpublished studies. We adapted the Newcastle-Ottawa Scale to sess the risk of bias. We estimated incidence and hospitalisation rates of influenza-virus-associated spiratory infections by severity, case ascertainment, region, and age. We estimated in-hospital deaths om influenza virus ALRI by combining hospital admissions and in-hospital case-fatality ratios of fluenza virus ALRI. We estimated the upper bound of influenza virus-associated ALRI deaths based on e number of in-hospital deaths, US paediatric influenza-associated death data, and population-based ildhood all-cause pneumonia mortality data in six sites in low-income and lower-middle-income untries.Findings: In 2018, among children under 5 years globally, there were an estimated 109.5 million fluenza virus episodes (uncertainty range [UR] 63.1-190.6), 10.1 million influenza-virus-associated ALRI ses (6.8-15.1); 870 000 influenza-virus-associated ALRI hospital admissions (543 000-1 415 000), 15 300 -hospital deaths (5800-43 800), and up to 34 800 (13 200-97 200) overall influenza-virus-associated ALRI deaths. Influenza virus accounted for 7% of ALRI cases, 5% of ALRI hospital admissions, and 4% of ALRI deaths in children under 5 years. About 23% of the hospital admissions and 36% of the in-hospital deaths were in infants under 6 months. About 82% of the in-hospital deaths occurred in low-income and lower-middle-income countries.Interpretation: A large proportion of the influenza-associated burden occurs among young infants and in low-income and lower middle-income countries. Our findings provide new and important evidence for maternal and paediatric influenza immunisation, and should inform future immunisation policy particularly in low-income and middle-income countries.
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