| 1. |
- Blokland, G. A. M., et al.
(författare)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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| 2. |
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| 3. |
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| 4. |
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| 5. |
- de Jong, S, et al.
(författare)
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Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
- 2018
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 1, s. 163-
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Tidskriftsartikel (refereegranskat)abstract
- Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.
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| 6. |
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| 7. |
- Arnau-Soler, A, et al.
(författare)
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Genome-wide by environment interaction studies of depressive symptoms and psychosocial stress in UK Biobank and Generation Scotland
- 2019
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1, s. 14-
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Tidskriftsartikel (refereegranskat)abstract
- Stress is associated with poorer physical and mental health. To improve our understanding of this link, we performed genome-wide association studies (GWAS) of depressive symptoms and genome-wide by environment interaction studies (GWEIS) of depressive symptoms and stressful life events (SLE) in two UK population-based cohorts (Generation Scotland and UK Biobank). No SNP was individually significant in either GWAS, but gene-based tests identified six genes associated with depressive symptoms in UK Biobank (DCC, ACSS3, DRD2, STAG1, FOXP2 and KYNU; p < 2.77 × 10−6). Two SNPs with genome-wide significant GxE effects were identified by GWEIS in Generation Scotland: rs12789145 (53-kb downstream PIWIL4; p = 4.95 × 10−9; total SLE) and rs17070072 (intronic to ZCCHC2; p = 1.46 × 10−8; dependent SLE). A third locus upstream CYLC2 (rs12000047 and rs12005200, p < 2.00 × 10−8; dependent SLE) when the joint effect of the SNP main and GxE effects was considered. GWEIS gene-based tests identified: MTNR1B with GxE effect with dependent SLE in Generation Scotland; and PHF2 with the joint effect in UK Biobank (p < 2.77 × 10−6). Polygenic risk scores (PRSs) analyses incorporating GxE effects improved the prediction of depressive symptom scores, when using weights derived from either the UK Biobank GWAS of depressive symptoms (p = 0.01) or the PGC GWAS of major depressive disorder (p = 5.91 × 10−3). Using an independent sample, PRS derived using GWEIS GxE effects provided evidence of shared aetiologies between depressive symptoms and schizotypal personality, heart disease and COPD. Further such studies are required and may result in improved treatments for depression and other stress-related conditions.
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| 8. |
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| 9. |
- Czamara, D, et al.
(författare)
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Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2548-
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Tidskriftsartikel (refereegranskat)abstract
- Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.
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| 10. |
- Bryant, J. M., et al.
(författare)
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Emergence and spread of a human-transmissible multidrug-resistant nontuberculous mycobacterium
- 2016
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 354:6313, s. 751-757
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Tidskriftsartikel (refereegranskat)abstract
- Lung infections with Mycobacterium abscessus, a species of multidrug-resistant nontuberculous mycobacteria, are emerging as an important global threat to individuals with cystic fibrosis (CF), in whom M. abscessus accelerates inflammatory lung damage, leading to increased morbidity and mortality. Previously, M. abscessus was thought to be independently acquired by susceptible individuals from the environment. However, using whole-genome analysis of a global collection of clinical isolates, we show that the majority of M. abscessus infections are acquired through transmission, potentially via fomites and aerosols, of recently emerged dominant circulating clones that have spread globally. We demonstrate that these clones are associated with worse clinical outcomes, show increased virulence in cell-based and mouse infection models, and thus represent an urgent international infection challenge.
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| 11. |
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| 13. |
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| 14. |
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| 15. |
- Stenström, P, et al.
(författare)
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Total colonic aganglionosis: multicentre study of surgical treatment and patient-reported outcomes up to adulthood.
- 2020
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Ingår i: BJS open. - 2474-9842. ; 4:5, s. 943-953
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Tidskriftsartikel (refereegranskat)abstract
- Surgery for total colonic aganglionosis (TCA) is designed to preserve continence and achieve satisfactory quality of life. This study evaluated a comprehensive group of clinical and social outcomes.An international multicentre study from eight Nordic hospitals involving examination of case records and a patient-reported questionnaire survey of all patients born with TCA between 1987 and 2006 was undertaken.Of a total of 116 patients, five (4·3 per cent) had died and 102 were traced. Over a median follow-up of 12 (range 0·3-33) years, bowel continuity was established in 75 (73·5 per cent) at a median age of 11 (0·5-156) months. Mucosectomy with a short muscular cuff and straight ileoanal anastomosis (SIAA) (29 patients) or with a J pouch (JIAA) (26) were the most common reconstructions (55 of 72, 76 per cent). Major early postoperative complications requiring surgical intervention were observed in four (6 per cent) of the 72 patients. In 57 children aged over 4 years, long-term functional bowel symptoms after reconstruction included difficulties in holding back defaecation in 22 (39 per cent), more than one faecal accident per week in nine (16 per cent), increased frequency of defaecation in 51 (89 per cent), and social restrictions due to bowel symptoms in 35 (61 per cent). Enterocolitis occurred in 35 (47 per cent) of 72 patients. Supplementary enteral and/or parenteral nutrition was required by 51 (55 per cent) of 93 patients at any time during follow-up. Of 56 responders aged 2-20 years, true low BMI for age was found in 20 (36 per cent) and 13 (23 per cent) were short for age.Reconstruction for TCA was associated with persistent bowel symptoms, and enterocolitis remained common. Multidisciplinary follow-up, including continuity of care in adulthood, might improve care standards in patients with TCA.
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| 16. |
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| 17. |
- Chatzikonstantinou, T, et al.
(författare)
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COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study
- 2021
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 35:12, s. 3444-3454
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Tidskriftsartikel (refereegranskat)abstract
- Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41–0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02–1.04; HR = 1.79, 95% CI:1.04–3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated.
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| 18. |
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| 19. |
- Skari, H, et al.
(författare)
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Congenital diaphragmatic hernia: a survey of practice in Scandinavia
- 2004
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Ingår i: Pediatric Surgery International. - : Springer Science and Business Media LLC. - 1437-9813 .- 0179-0358. ; 20:5, s. 309-313
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Tidskriftsartikel (refereegranskat)abstract
- There is no consensus on the treatment of congenital diaphragmatic hernia (CDH), and practice seems to vary between centres. The main purpose of the present study was to survey current practice in Scandinavia. Thirteen paediatric surgical centres serving a population of about 22 million were invited, and all participated. One questionnaire was completed at each centre. The questionnaire evaluated management following prenatal diagnosis, intensive care strategies, operative treatment, and long-term follow-up. Survival data (1995-1998) were available from 12 of 13 centres. Following prenatal diagnosis of CDH, vaginal delivery and maternal steroids were used at eight and six centres, respectively. All centres used high-frequency oscillation ventilation (HFOV), nitric oxide (NO), and surfactant comparatively often. Five centres had extracorporeal membrane oxygenation (ECMO) facilities, and four centres transferred ECMO candidates. The majority of centres (7/9) always tried HFOV before ECMO was instituted. Surgery was performed when the neonate was clinically stable (11/13) and when no signs of pulmonary hypertension were detected by echo-Doppler (6/13). The repair was performed by laparotomy at all centres and most commonly with nonabsorbable sutures (8/13). Thoracic drain was used routinely at seven centres. Long-term follow-up at a paediatric surgical centre was uncommon (3/13). Only three centres treated more than five CDH patients per year. Comparing survival in centres treating more than five with those treating five or fewer CDH patients per year, there was a tendency towards better survival in the higher-volume centres (72.4%) than in the centres with lower volume (58.7%), p =0.065.
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| 20. |
- Sperling, L., et al.
(författare)
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Detection of chromosomal abnormalities, congenital abnormalities and transfusion syndrome in twins
- 2007
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Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 29:5, s. 517-526
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Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate the outcome of screening for structural malformations in twins and the outcome of screening for twin-twin transfusion syndrome (TTTS) among monochorionic twins through a number of ultrasound scans from 12 weeks' gestation. Methods Enrolled into this prospective multicenter observational study were women with twin pregnancies diagnosed before 14 + 6 gestational weeks. The monochorionic pregnancies were scanned every second week until 23 weeks in order to rule out early TTTS. All pregnancies had an anomaly scan in week 19 and fetal echocardiography in week 21 that was performed by specialists in fetal echocardiography. Zygosity was determined by DNA analysis in all twin pairs with the same sex. Results Among the 495 pregnancies the prenatal detection rate for severe structural abnormalities including chromosomal aneuploidies was 83% by the combination of a first-trimester nuchal translucency scan and the anomaly scan in week 19. The incidence of severe structural abnormalities was 2.6% and two-thirds of these anomalies were cardiac. There was no significant difference between the incidence in monozygotic and dizygotic twins, nor between twins conceived naturally or those conceived by assisted reproduction. The incidence of TTTS was 23% from 12 weeks until delivery, and all those monochorionic twin pregnancies that miscarried had signs of TTTS. Conclusion Twin pregnancies have an increased risk of congenital malformations and one out of four monochorionic pregnancies develops TTTS. Ultrasound screening to assess chorionicity and follow-up of monochorionic pregnancies to detect signs of TTTS, as well as malformation screening, are therefore essential in the antenatal care of twin pregnancies. Copyright (c) 2007 IS UOG. Published by John Wiley & Sons, Ltd.
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| 21. |
- Sperling, L, et al.
(författare)
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How to identify twins at low risk of spontaneous preterm delivery
- 2005
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Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 26:2, s. 138-144
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Tidskriftsartikel (refereegranskat)abstract
- Objective The aim of this study was to evaluate transvaginal sonograpbic assessment of cervical length at 23 weeks as a screening test for spontaneous preterm delivery in order to define a cut-off value that could be used to select twin pregnancies at low risk of spontaneous preterm delivery. Methods In a prospective multicenter study of 383 twin pregnancies included before 14 + 6 weeks a cervical scan with measurement of the cervical length was performed at 23 weeks' gestation. The results were blinded for the clinicians if the cervical length was >= 15 mm. The rates of spontaneous delivery at different cut-off levels of cervical length were determined. Results Eighty-nine percent of the twins had dichorionic placentation and 58% were conceived after assisted reproduction. The rate of spontaneous preterm delivery was 2.3% (1.5% for dichorionic (DC) and 9.1% for (MC) monochorionic twins) before 28 weeks and 18.5% (17.1% for DC and 29.5% for MC twins) before 35 weeks. The screen-positive rate was 5% for a cervical length <= 20, 7-8% at <= 25, 16-17% at <= 30 and 34-48% at <= 35mm depending on chorionicity. The false-negative rate (1 - negative predictive value) ranged from 1.2% at 28 weeks to 18.6% at 35 weeks for all twins. Receiver-operating characteristics curves showed that the sensitivity increased with declining gestation I age with cut-off levels of highest accuracy at 21 mm for 28 weeks and 29 mm for 33 weeks. Conclusions Cervical length measurement at 23 weeks of gestation is a good screening test for predicting twins at low risk of preterm and very preterm delivery, especially in DC twins. The present results suggest that a cut-off of 25 mm should be recommended.
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| 22. |
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| 23. |
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| 24. |
- Johansson, SE, et al.
(författare)
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Smokeless tobacco and coronary heart disease: a 12-year follow-up study
- 2005
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Ingår i: European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology. - : Oxford University Press (OUP). - 1741-8267. ; 12:4, s. 387-392
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Tidskriftsartikel (refereegranskat)abstract
- Background Cigarette smoking has declined whereas the use of smokeless tobacco is increasing. There is an ongoing debate as to whether smokeless tobacco is a recommendable strategy to help smokers to quit. However, very few studies have examined the association between smokeless tobacco, namely snuff, and coronary heart disease, which implies that it has not been possible to provide scientific results for public health policies and clinical guidelines concerning the use of smokeless tobacco. Design A follow-up study. Methods A random sample of 3120 healthy men aged 30–74 years was interviewed in 1988 and 1989 and followed up to the year 2000 with regard to coronary heart disease. Cox regression was used to estimate the relative risk of coronary heart disease in six categories of smoking and snuffing habits, after adjustment for established risk factors for coronary heart disease. Results Smokers, former smokers, and those who combined smoking and snuffing had significantly higher hazard ratios than never-smokers. The very highest hazard ratio was found among individuals combining smoking and snuffing. Daily snuffers had a hazard ratio of 1.62 (95% confidence interval 0.70–3.03) after adjustment for age. Conclusions Even though the association between daily snuffing and coronary heart disease was non-significant, the hazard ratio was markedly increased. Therefore, smokers should not use smokeless tobacco in order to quit smoking, especially as safer alternatives are available. Further studies in different settings are required to provide scientific results for public health policies and clinical guidelines.
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| 25. |
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| 26. |
- Pakarinen, M, et al.
(författare)
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Centralized Pediatric Surgery in the Nordic Countries: A Role Model for Europe?
- 2017
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Ingår i: European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift fur Kinderchirurgie. - : Georg Thieme Verlag KG. - 1439-359X. ; 27:5, s. 395-398
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Tidskriftsartikel (refereegranskat)abstract
- Nearly all neonatal surgical conditions are classified as rare diseases in Europe. Due to rapidly developing treatment modalities and novel surgical techniques, as well as increasing demands from patients, there is a growing need for centralization of advanced pediatric surgical care. However, the optimal way to concentrate pediatric surgical experience in each country remains unclear and depends on multiple national features, such as size and distribution of the population, geographical distances, local surgical expertise, organization of the health care system, and political agendas. This review outlines the current practices to concentrate on specialized pediatric surgery in different Nordic countries.
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| 27. |
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| 28. |
- Sperling, L., et al.
(författare)
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Naturally conceived twins with monochorionic placentation have the highest risk of fetal loss
- 2006
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Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 28:5, s. 644-652
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Tidskriftsartikel (refereegranskat)abstract
- Objective The aim of this study was to estimate the rate of fetal loss in dichorionic (DC) and monochorionic (MC) twin pregnancies stratified according to zygosity and method of conception. Methods In a prospective multicenter observational study women with a twin pregnancy bad an ultrasound scan before 14 + 6 weeks' gestation in order to determine chorionicity. The fetal loss rate, the perinatal, neonatal and infant mortality rates and the frequency of very preterm labor were estimated for the different types of twin. Results Among the 495 pregnancies (421 DC and 74 MC) 229 (46%) were conceived naturally and 266 (54%) by assisted reproduction (AR). Outcome data for 945 liveborn babies were obtained. The spontaneous miscarriage rate before 24 weeks' gestation was 10.9% (7164) among naturally conceived MC compared to 3.0% (51165) for naturally conceived DC twins (P < 0.05). For twins conceived by AR the corresponding figures were 0% (0/10) and 0.4% (1/256). The odds ratio (OR) for very preterm birth - before 28 weeks'gestation - was 4.2 for MC twins compared to DC twins. The relative risk of fetal loss or death among DC twins was 20% of the risk for MC twins. Conclusion The risk of fetal loss, very preterm delivery and neonatal/infant death is significantly higher among twins with MC compared to DC placentation. Twins conceived by AR have a much lower risk of MC placentation. The risk of losing one or both twins seems higher among naturally conceived twins compared to twins conceived by AR, despite the fact that the maternal age was higher among the mothers of the AR twins. Copyright (c) 2006 ISUOG. Published by John Wiley & Sons, Ltd.
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| 29. |
- Sundquist, K, et al.
(författare)
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Does occupational social class predict coronary heart disease after retirement? A 12-year follow-up study in Sweden
- 2005
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Ingår i: Scandinavian journal of public health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 33:6, s. 447-454
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To examine whether socioeconomic status and coronary heart disease (CHD) risk factors remain significant predictors of CHD among people aged ≥65 years. Previous studies in this age group are few and inconsistent. Methods: Follow-up study of a simple random sample of Swedish women and men aged ≥65 years interviewed in a national survey 1988—89 and followed up until 31 December 2000, for CHD incidence rates. Cox regression was used to study the association between socioeconomic status (occupation) and CHD, after adjustment for age, sex, physical activity, smoking, BMI, diabetes, and hypertension. Participants with CHD hospitalization two years before the start of the study and those who rated their general health as poor were excluded. Results: Among manual workers and lower-level employees the risk of CHD was significantly higher than among middle-level employees and professionals (49% and 50%, respectively), after adjustment for age and sex. The association between low socioeconomic status and increased CHD risk disappeared after adjustment for the CHD risk factors, which were more prevalent among those with low socioeconomic status. All the CHD risk factors (with the exception of BMI) were associated with increased CHD incidence rates. Conclusions: Low socioeconomic status remains a significant predictor of CHD among people aged ≥65 years. Healthcare policies among elderly patients should encourage physical activity and smoking cessation in all socioeconomic groups.
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| 30. |
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| 31. |
- Sundquist, K, et al.
(författare)
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Increasing trends of obesity in Sweden between 1996/97 and 2000/01
- 2004
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Ingår i: International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity. - : Springer Science and Business Media LLC. - 0307-0565. ; 28:2, s. 254-261
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Tidskriftsartikel (refereegranskat)
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| 33. |
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