| 1. |
- Oddsson, Asmundur, et al.
(författare)
-
Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality
- 2023
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Genotypes causing pregnancy loss and perinatal mortality are depleted among living individuals and are therefore difficult to find. To explore genetic causes of recessive lethality, we searched for sequence variants with deficit of homozygosity among 1.52 million individuals from six European populations. In this study, we identified 25 genes harboring protein-altering sequence variants with a strong deficit of homozygosity (10% or less of predicted homozygotes). Sequence variants in 12 of the genes cause Mendelian disease under a recessive mode of inheritance, two under a dominant mode, but variants in the remaining 11 have not been reported to cause disease. Sequence variants with a strong deficit of homozygosity are over-represented among genes essential for growth of human cell lines and genes orthologous to mouse genes known to affect viability. The function of these genes gives insight into the genetics of intrauterine lethality. We also identified 1077 genes with homozygous predicted loss-of-function genotypes not previously described, bringing the total set of genes completely knocked out in humans to 4785.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Grånäs, Elin, et al.
(författare)
-
Water Chemistry beneath Graphene : Condensation of a Dense OH-H2O Phase under Graphene
- 2022
-
Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 126:9, s. 4347-4354
-
Tidskriftsartikel (refereegranskat)abstract
- Room temperature oxygen hydrogenation below graphene flakes supported by Ir(111) is investigated through a combination of X-ray photoelectron spectroscopy, scanning tunneling microscopy, and density functional theory calculations using an evolutionary search algorithm. We demonstrate how the graphene cover and its doping level can be used to trap and characterize dense mixed O-OH-H2O phases that otherwise would not exist. Our study of these graphene-stabilized phases and their response to oxygen or hydrogen exposure reveals that additional oxygen can be dissolved into them at room temperature creating mixed O-OH-H2O phases with an increased areal coverage underneath graphene. In contrast, additional hydrogen exposure converts the mixed O-OH-H2O phases back to pure OH-H2O with a reduced areal coverage underneath graphene.
|
|
| 7. |
|
|
| 8. |
- Kalaria, Raj, et al.
(författare)
-
The 2022 symposium on dementia and brain aging in low- and middle-income countries: Highlights on research, diagnosis, care, and impact.
- 2024
-
Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - 1552-5279.
-
Tidskriftsartikel (refereegranskat)abstract
- Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC-focused research to ensure that characterization of dementia accurately reflects the involvement and specificities of diverse populations. Development of effective preventive, diagnostic, and therapeutic approaches for dementia in LMICs requires targeted, personalized, and harmonized efforts. Our article represents timely discussions at the 2022 Symposium on Dementia and Brain Aging in LMICs that identified the foremost opportunities to advance dementia research, differential diagnosis, use of neuropsychometric tools, awareness, and treatment options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. HIGHLIGHTS: Two-thirds of persons with dementia live in LMICs, yet research and costs are skewed toward HICs. LMICs expect dementia prevalence to more than double, accompanied by socioeconomic disparities. The 2022 Symposium on Dementia in LMICs addressed advances in research, diagnosis, prevention, and policy. The Nairobi Declaration urges global action to enhance dementia outcomes in LMICs.
|
|
| 9. |
|
|
| 10. |
- Merritt, Melissa A., et al.
(författare)
-
Nutrient-wide association study of 57 foods/nutrients and epithelial ovarian cancer in the European Prospective Investigation into Cancer and Nutrition study and the Netherlands Cohort Study
- 2016
-
Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 103:1, s. 161-167
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of the role of dietary factors in epithelial ovarian cancer (EOC) development have been limited, and no specific dietary factors have been consistently associated with EOC risk.Objective: We used a nutrient-wide association study approach to systematically test the association between dietary factors and invasive EOC risk while accounting for multiple hypothesis testing by using the false discovery rate and evaluated the findings in an independent cohort.Design: We assessed dietary intake amounts of 28 foods/food groups and 29 nutrients estimated by using dietary questionnaires in the EPIC (European Prospective Investigation into Cancer and Nutrition) study (n = 1095 cases). We selected 4 foods/nutrients that were statistically significantly associated with EOC risk when comparing the extreme quartiles of intake in the EPIC study (false discovery rate = 0.43) and evaluated these factors in the NLCS (Netherlands Cohort Study; n = 383 cases). Cox regression models were used to estimate HRs and 95% CIs.Results: None of the 4 dietary factors that were associated with EOC risk in the EPIC study (cholesterol, polyunsaturated and saturated fat, and bananas) were statistically significantly associated with EOC risk in the NLCS; however, in meta-analysis of the EPIC study and the NLCS, we observed a higher risk of EOC with a high than with a low intake of saturated fat (quartile 4 compared with quartile 1; overall HR: 1.21; 95% CI: 1.04, 1.41).Conclusion: In the meta-analysis of both studies, there was a higher risk of EOC with a high than with a low intake of saturated fat.
|
|
| 11. |
- Westergaard, David, et al.
(författare)
-
Genome-wide association meta-analysis identifies five loci associated with postpartum hemorrhage.
- 2024
-
Ingår i: Nature genetics. - 1546-1718.
-
Tidskriftsartikel (refereegranskat)abstract
- Bleeding in early pregnancy and postpartum hemorrhage (PPH) bear substantial risks, with the former closely associated with pregnancy loss and the latter being the foremost cause of maternal death, underscoring the severe impact on maternal-fetal health. We identified five genetic loci linked to PPH in a meta-analysis. Functional annotation analysis indicated candidate genes HAND2, TBX3 and RAP2C/FRMD7 at three loci and showed that at each locus, associated variants were located within binding sites for progesterone receptors. There were strong genetic correlations with birth weight, gestational duration and uterine fibroids. Bleeding in early pregnancy yielded no genome-wide association signals but showed strong genetic correlation with various human traits, suggesting a potentially complex, polygenic etiology. Our results suggest that PPH is related to progesterone signaling dysregulation, whereas early bleeding is a complex trait associated with underlying health and possibly socioeconomic status and may include genetic factors that have not yet been identified.
|
|
| 12. |
- Bennett, Sarah E., et al.
(författare)
-
Assessing acceptability and identifying barriers and facilitators to implementation of the EULAR recommendations for patient education in inflammatory arthritis : a mixed-methods study with rheumatology professionals in 23 European and Asian countries
- 2022
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 81:10, s. 1348-1357
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: To disseminate and assess the level of acceptability and applicability of the European Alliance of Associations for Rheumatology (EULAR) recommendations for patient education among professionals in rheumatology across Europe and three Asian countries and identify potential barriers and facilitators to their application. Methods: A parallel convergent mixed-methods design with an inductive approach was used. A web-based survey, available in 20 different languages, was distributed to health professionals by non-probability sampling. The level of agreement and applicability of each recommendation was assessed by (0-10) rating scales. Barriers and facilitators to implementation were assessed using free-text responses. Quantitative data were analysed descriptively and qualitative data by content analysis and presented in 16 categories supported by quotes. Results: A total of 1159 completed the survey; 852 (73.5%) were women. Most of the professionals were nurses (n=487), rheumatologists (n=320), physiotherapists (n=158). For all recommendations, the level of agreement was high but applicability was lower. The four most common barriers to application were lack of time, lack of training in how to provide patient education, not having enough staff to perform this task and lack of evaluation tools. The most common facilitators were tailoring patient education to individual patients, using group education, linking patient education with diagnosis and treatment and inviting patients to provide feedback on patient education delivery.Conclusions: This project has disseminated the EULAR recommendations for patient education to health professionals across 23 countries. Potential barriers to their application were identified and some are amenable to change, namely training patient education providers and developing evaluation tools. © Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.
|
|
| 13. |
- Besevic, Jelena, et al.
(författare)
-
Reproductive factors and epithelial ovarian cancer survival in the EPIC cohort study
- 2015
-
Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 113:11, s. 1622-1631
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Reproductive factors influence the risk of developing epithelial ovarian cancer (EOC), but little is known about their association with survival. We tested whether prediagnostic reproductive factors influenced EOC-specific survival among 1025 invasive EOC cases identified in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, which included 521 330 total participants (approximately 370 000 women) aged 25-70 years at recruitment from 1992 to 2000. Methods: Information on reproductive characteristics was collected at recruitment. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), and multivariable models were adjusted for age and year of diagnosis, body mass index, tumour stage, smoking status and stratified by study centre. Results: After a mean follow-up of 3.6 years (+/- 3.2 s.d.) following EOC diagnosis, 511 (49.9%) of the 1025 women died from EOC. We observed a suggestive survival advantage in menopausal hormone therapy (MHT) users (ever vs never use, HR = 0.80, 95% CI = 0.62-1.03) and a significant survival benefit in long-term MHT users (>= 5 years use vs never use, HR = 0.70, 95% CI = 0.50-0.99, P-trend = 0.04). We observed similar results for MHT use when restricting to serous cases. Other reproductive factors, including parity, breastfeeding, oral contraceptive use and age at menarche or menopause, were not associated with EOC-specific mortality risk. Conclusions: Further studies are warranted to investigate the possible improvement in EOC survival in MHT users.
|
|
| 14. |
- Campa, Daniele, et al.
(författare)
-
Leukocyte telomere length in relation to pancreatic cancer risk: a prospective study.
- 2014
-
Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755 .- 1055-9965. ; 23:11, s. 2447-2454
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Several studies have examined leukocyte telomere length (LTL) as a possible predictor for cancer at various organ sites. The hypothesis originally motivating many of these studies was that shorter telomeres would be associated with an increase in cancer risk, the results of epidemiologic studies have been inconsistent, however, and suggested positive, negative, or null associations. Two studies have addressed the association of LTL in relation to pancreatic cancer risk and the results are contrasting. Methods: we measured LTL in a prospective study of 331 pancreatic cancer cases and 331 controls in the context of the European Prospective Investigation into Cancer and Nutrition (EPIC). Results: We observed that the mean LTL was higher in cases (0.59±0.20) than in controls (0.57±0.17), although this difference was not statistically significant (p=0.07), and a basic logistic regression model showed no association of LTL with pancreas cancer risk. When adjusting for levels of HbA1c and C-Peptide, however, there was a weakly positive association between longer LTL and pancreatic cancer risk , OR=1.13 (1.01-1.27). Additional analyses by cubic spline regression suggested a possible non-linear relationship between RTL and pancreatic cancer risk (P=0.022), with a statistically non-significant increase in risk at very low LTL, as well as a significant increase at high LTL. Conclusion: Taken together, the results from our study do not support LTL as a uniform and strong predictor of pancreatic cancer. Impact: The results of this manuscript can provide insights into telomere dynamics and highlight the complex relationship between LTL and pancreatic cancer risk.
|
|
| 15. |
|
|
| 16. |
- Fortner, Renee T., et al.
(författare)
-
Correlates of circulating ovarian cancer early detection markers and their contribution to discrimination of early detection models : results from the EPIC cohort
- 2017
-
Ingår i: Journal of Ovarian Research. - : Springer Science and Business Media LLC. - 1757-2215. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Ovarian cancer early detection markers CA125, CA15.3, HE4, and CA72.4 vary between healthy women, limiting their utility for screening.Methods: We evaluated cross-sectional relationships between lifestyle and reproductive factors and these markers among controls (n = 1910) from a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC). Improvements in discrimination of prediction models adjusting for correlates of the markers were evaluated among postmenopausal women in the nested case-control study (n = 590 cases). Generalized linear models were used to calculate geometric means of CA125, CA15.3, and HE4. CA72.4 above vs. below limit of detection was evaluated using logistic regression. Early detection prediction was modeled using conditional logistic regression.Results: CA125 concentrations were lower, and CA15.3 higher, in post- vs. premenopausal women (p ≤ 0.02). Among postmenopausal women, CA125 was higher among women with higher parity and older age at menopause (ptrend ≤ 0.02), but lower among women reporting oophorectomy, hysterectomy, ever use of estrogen-only hormone therapy, or current smoking (p < 0.01). CA15.3 concentrations were higher among heavier women and in former smokers (p ≤ 0.03). HE4 was higher with older age at blood collection and in current smokers, and inversely associated with OC use duration, parity, and older age at menopause (≤ 0.02). No associations were observed with CA72.4. Adjusting for correlates of the markers in prediction models did not improve the discrimination.Conclusions: This study provides insights into sources of variation in ovarian cancer early detection markers in healthy women and informs about the utility of individualizing marker cutpoints based on epidemiologic factors.
|
|
| 17. |
- Grånäs, Elin, et al.
(författare)
-
CO Intercalation of Graphene on Ir(111) in the Millibar Regime
- 2013
-
Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 117:32, s. 16438-16447
-
Tidskriftsartikel (refereegranskat)abstract
- Here we show that it is possible to intercalate CO under graphene grown on Ir(111) already at room temperature when CO pressures in the millibar regime are used. From the interplay of X-ray photoelectron spectroscopy and scanning tunneling microscopy we conclude that the intercalated CO adsorption structure is similar to the (3 root 3 X 3 root 3)R30 degrees) adsorption structure that is formed on Ir(111) upon exposure to similar to 1 mbar of CO. Further, density functional theory calculations reveal that the structural and electronic properties of CO-intercalated graphene are similar to p-doped freestanding graphene. Finally we characterize nonintercalated stripes and islands that we always observe in the CO-intercalated graphene. We observe these nonintercalated areas predominately in HCP and FCC areas near step edges and suggest that stress release in graphene is the driving force for their formation, while the weak chemical bonds in HCP and FCC areas are the reason for their area selectivity.
|
|
| 18. |
|
|
| 19. |
- Mie, A, et al.
(författare)
-
Correction to: Response to Juberg et al
- 2020
-
Ingår i: Environmental health : a global access science source. - : Springer Science and Business Media LLC. - 1476-069X. ; 19:1, s. 76-
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- An amendment to this paper has been published and can be accessed via the original article.
|
|
| 20. |
- Moslemi, Camous, et al.
(författare)
-
A large cohort study of the effects of Lewis, ABO, 13 other blood groups, and secretor status on COVID-19 susceptibility, severity, and long COVID-19
- 2023
-
Ingår i: Transfusion. - : Wiley. - 0041-1132 .- 1537-2995. ; 63:1, s. 47-58
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Previous studies have reported Blood type O to confer a lower risk of SARS-CoV-2 infection, while secretor status and other blood groups have been suspected to have a similar effect as well. Study design and methods: To determine whether any other blood groups influence testing positive for SARS-CoV-2, COVID-19 severity, or prolonged COVID-19, we used a large cohort of 650,156 Danish blood donors with varying available data for secretor status and blood groups ABO, Rh, Colton, Duffy, Diego, Dombrock, Kell, Kidd, Knops, Lewis, Lutheran, MNS, P1PK, Vel, and Yt. Of these, 36,068 tested positive for SARS-CoV-2 whereas 614,088 tested negative between 2020-02-17 and 2021-08-04. Associations between infection and blood groups were assessed using logistic regression models with sex and age as covariates. Results: The Lewis blood group antigen Lea displayed strongly reduced SARS-CoV-2 susceptibility OR 0.85 CI[0.79–0.93] p <.001. Compared to blood type O, the blood types B, A, and AB were found more susceptible toward infection with ORs 1.1 CI[1.06–1.14] p <.001, 1.17 CI[1.14–1.2] p <.001, and 1.2 CI[1.14–1.26] p <.001, respectively. No susceptibility associations were found for the other 13 blood groups investigated. There was no association between any blood groups and COVID-19 hospitalization or long COVID-19. No secretor status associations were found. Discussion: This study uncovers a new association to reduced SARS-CoV-2 susceptibility for Lewis type Lea and confirms the previous link to blood group O. The new association to Lea could be explained by a link between mucosal microbiome and SARS-CoV-2.
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
- Skotte, Line, et al.
(författare)
-
Genome-wide association study of febrile seizures implicates fever response and neuronal excitability genes
- 2022
-
Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 145:2, s. 555-568
-
Tidskriftsartikel (refereegranskat)abstract
- Febrile seizures represent the most common type of pathological brain activity in young children and are influenced by genetic, environmental and developmental factors. In a minority of cases, febrile seizures precede later development of epilepsy. We conducted a genome-wide association study of febrile seizures in 7635 cases and 83 966 controls identifying and replicating seven new loci, all with P < 5 × 10-10. Variants at two loci were functionally related to altered expression of the fever response genes PTGER3 and IL10, and four other loci harboured genes (BSN, ERC2, GABRG2, HERC1) influencing neuronal excitability by regulating neurotransmitter release and binding, vesicular transport or membrane trafficking at the synapse. Four previously reported loci (SCN1A, SCN2A, ANO3 and 12q21.33) were all confirmed. Collectively, the seven novel and four previously reported loci explained 2.8% of the variance in liability to febrile seizures, and the single nucleotide polymorphism heritability based on all common autosomal single nucleotide polymorphisms was 10.8%. GABRG2, SCN1A and SCN2A are well-established epilepsy genes and, overall, we found positive genetic correlations with epilepsies (rg = 0.39, P = 1.68 × 10-4). Further, we found that higher polygenic risk scores for febrile seizures were associated with epilepsy and with history of hospital admission for febrile seizures. Finally, we found that polygenic risk of febrile seizures was lower in febrile seizure patients with neuropsychiatric disease compared to febrile seizure patients in a general population sample. In conclusion, this largest genetic investigation of febrile seizures to date implicates central fever response genes as well as genes affecting neuronal excitability, including several known epilepsy genes. Further functional and genetic studies based on these findings will provide important insights into the complex pathophysiological processes of seizures with and without fever.
|
|
| 25. |
- Wiese, Mie, et al.
(författare)
-
Influence of cross-sectional temporomandibular joint (TMJ) tomography on diagnosis and management of patients with temporomandibular disorders (TMD)
- 2008
-
Konferensbidrag (refereegranskat)abstract
- Objectives: To describe changes in diagnosis and management of TMD patients after radiographic examination and to evaluate the associations between specific TMJ tomographic findings and changes in management. Methods: 204 adult patients (48 males, 156 females, mean age 40 years) with TMJ pain/sounds or problems with mandibular motion were examined according to the Research Diagnostic Criteria (RDC/TMD) by one of six calibrated orofacial pain specialists. Diagnoses and management strategy reached without the aid of radiographs were recorded. It was possible to select from seven management categories (pharmacology, physiotherapy, psychological, occlusal stabilization, surgical, other examinations and referrals) each with a number of sub-categories. Bilateral sagittal corrected TMJ tomograms in closed position were obtained using conventional film in a Cranex Tome or a Scanora tomographic X-ray unit. The tomograms were assessed for the presence of flattening, erosion, osteophyte and sclerosis in the TMJ components and the condyle-to-mandibular fossa relation by one of five calibrated oral radiologists blinded to the clinical diagnosis and initial management strategy. After gaining access to the results from the radiographic examination the orofacial pain specialists re-evaluated their diagnoses and management strategy. All changes were calculated. Logistic regression analyses (with odds ratio (OR) and significance level (p)) were performed with changes in management as the dependent variable and with age and radiographic findings as the independent variables. Results: 41% of the clinical arthralgia diagnoses were changed into osteoarthritis after radiographic examination and the number of osteoarthrosis diagnoses increased with 200% (from 13 to 39). One or more changes in the management strategy were found for 27% (55) of the patients. Most often changes occurred in pharmacology and physiotherapy (29 and 28 patients respectively) followed by changes in psychological (13 patients), occlusal stabilization (8 patients), referrals (7 patients), other examinations (6 patients) and surgical (2 patients). For pharmacology, physiotherapy and psychological the changes were adjustments within the sub-categories in 51 out of 70 patients. For the other management categories most of the changes were addition or omission of the management category (in 20 out of 23 patients). The chance of “any change” in management (removal or addition of one or more sub-categories in one or more management categories) was more than twice as high with a finding of flattening (OR=2.28) and erosion (OR=2.03) compared to not having these radiographic findings. Increased chance of “any change” in management was also found with >1 radiographic finding (regardless of type) (OR=2.64) compared to having no radiographic findings. The chance of change in pharmacology was increased more than three times with erosion (OR=3.60) and more than two times with flattening (OR=2.56). The chance of change in physiotherapy was increased with >1 radiographic finding (OR=2.79). No statistically significant (p≤0.05) associations between osteophyte, sclerosis and age and changes in management were found. Conclusion: 27% of the patients had changes in management after radiographic examination. Radiographic findings did increase the chance of changes in management. However, as the changes were mostly adjustments in sub-categories radiography may have a minor impact on management of most TMD patients.
|
|
