| 1. |
- Kanai, M, et al.
(författare)
-
- 2023
-
swepub:Mat__t
|
|
| 2. |
- Niemi, MEK, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 3. |
- Kanoni, Stavroula, et al.
(författare)
-
Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
-
Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
|
|
| 4. |
- Lagou, Vasiliki, et al.
(författare)
-
Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
- 2021
-
Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
|
|
| 5. |
- de las Fuentes, Lisa, et al.
(författare)
-
Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci
- 2021
-
Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:6, s. 2111-2125
-
Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, “Some College” (yes/no) and “Graduated College” (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
|
|
| 6. |
- Huang, Liping, et al.
(författare)
-
The impact of baseline potassium intake on the dose-response relation between sodium reduction and blood pressure change : systematic review and meta-analysis of randomized trials.
- 2021
-
Ingår i: Journal of Human Hypertension. - : Springer Nature. - 0950-9240 .- 1476-5527. ; 35:11, s. 946-957
-
Tidskriftsartikel (refereegranskat)abstract
- Sodium and potassium appear to interact with each other in their effects on blood pressure with potassium supplementation having a greater blood pressure lowering-effect when sodium intake is high. Whether the effect of sodium reduction on blood pressure varies according to potassium intake levels is unclear. We carried out a systematic review and meta-analysis to examine the impact of baseline potassium intake on blood pressure response to sodium reduction in randomized trials in adult populations, with sodium and potassium intake estimated from 24-h urine samples. We included 68 studies involving 5708 participants and conducted univariable and multivariable meta-regression. The median intake of baseline potassium was 67.7 mmol (Interquartile range: 54.6-76.4 mmol), and the mean reduction in sodium intake was 128 mmol (95% CI: 107-148). Multivariable meta-regression that included baseline 24-h urinary potassium excretion, age, ethnicity, baseline blood pressure, change in 24-h urinary sodium excretion, as well as the interaction between baseline 24-h urinary potassium excretion and change in 24-h urinary sodium excretion did not identify a significant association of baseline potassium intake levels with the blood pressure reduction achieved with a 50 mmol lowering of sodium intake (p > 0.05 for both systolic and diastolic blood pressure). A higher starting level of blood pressure was consistently associated with a greater blood pressure reduction from reduced sodium consumption. However, the nonsignificant findings may subject to the limitations of the data available. Additional studies with more varied potassium intake levels would allow a more confident exclusion of an interaction.
|
|
| 7. |
- Jang, Seon-Kyeong, et al.
(författare)
-
Rare genetic variants explain missing heritability in smoking.
- 2022
-
Ingår i: Nature human behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 6:11, s. 1577-1586
-
Tidskriftsartikel (refereegranskat)abstract
- Common genetic variants explain less variation in complex phenotypes than inferred from family-based studies, and there is a debate on the source of this 'missing heritability'. We investigated the contribution of rare genetic variants to tobacco use with whole-genome sequences from up to 26,257 unrelated individuals of European ancestries and 11,743 individuals of African ancestries. Across four smoking traits, single-nucleotide-polymorphism-based heritability ([Formula: see text]) was estimated from 0.13 to 0.28 (s.e., 0.10-0.13) in European ancestries, with 35-74% of it attributable to rare variants with minor allele frequencies between 0.01% and 1%. These heritability estimates are 1.5-4 times higher than past estimates based on common variants alone and accounted for 60% to 100% of our pedigree-based estimates of narrow-sense heritability ([Formula: see text], 0.18-0.34). In the African ancestry samples, [Formula: see text] was estimated from 0.03 to 0.33 (s.e., 0.09-0.14) across the four smoking traits. These results suggest that rare variants are important contributors to the heritability of smoking.
|
|
| 8. |
- Lester, Mark, et al.
(författare)
-
The Impact of Energetic Particles on the Martian Ionosphere During a Full Solar Cycle of Radar Observations: Radar Blackouts
- 2022
-
Ingår i: Journal of Geophysical Research - Space Physics. - : John Wiley & Sons. - 2169-9380 .- 2169-9402. ; 127:2
-
Tidskriftsartikel (refereegranskat)abstract
- We present the first long-term characterization of ionization layers in the lower ionosphere of Mars (below ∼90 km), a region inaccessible to orbital in-situ observations, based on an analysis of radar echo blackouts observed on Mars Express and the Mars Reconnaissance Orbiter from 2006 to 2017. A blackout occurs when the expected surface reflection is partly or totally attenuated for portions of an observation. Enhanced ionization at altitudes of 60–90 km, below the main ionospheric electron density peak, leads to increased absorption of the radar signal, resulting in the blackouts. We find that (a) MARSIS, operating at frequencies between 1.8 and 5 MHz, suffered more blackouts than SHARAD, which has a higher carrier frequency (20 MHz), (b) there is a clear correlation of blackout occurrence with solar cycle, (c) there is no apparent relationship between blackout occurrence and crustal magnetic fields, and (d) blackouts occur during both nightside and dayside observations, although the peak occurrence is deep on the nightside. Analysis of Mars Atmosphere and Volatile EvolutioN Solar Energetic Particle electron counts between 20 and 200 keV demonstrates that these electrons are likely responsible for attenuating the radar signals. We investigate the minimum SEP electron fluxes required to ionize the lower atmosphere and produce measurable attenuation. When both radars experience a blackout, the SEP electron fluxes are at their highest. Based on several case studies, we find that the average SEP spectrum responsible for a blackout is particularly enhanced at its higher energy end, that is, above 70 keV.
|
|
| 9. |
- Loeffen, Erik A. H., et al.
(författare)
-
Reducing pain and distress related to needle procedures in children with cancer : A clinical practice guideline
- 2020
-
Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 131, s. 53-67
-
Forskningsöversikt (refereegranskat)abstract
- Background: Children with cancer often undergo long treatment trajectories involving repeated needle procedures that potentially cause pain and distress. As part of a comprehensive effort to develop clinical practice guidelines (CPGs) to address pain prevention and management in children with cancer, we aimed to provide recommendations on the pharmacological and psychological management of procedure-related pain and distress.Methods: Of the international inter-disciplinary CPG development panel (44 individuals), two working groups including 13 healthcare professionals focused on procedural pain and distress. Grading of Recommendations Assessment, Development and Evaluation methodology was used, including the use of systematic literature reviews to inform recommendations and the use of evidence to decision frameworks. At an in-person meeting in February 2018, the guideline panel discussed these frameworks and formulated recommendations which were then discussed with a patient-parent panel consisting of 4 survivors and 5 parents.Results: The systematic reviews led to the inclusion of 48 randomised controlled trials (total number of participants = 2271). Quality of evidence supporting the recommendations ranged from very low to moderate. Strong recommendations were made for the use of topical anesthetics in all needle procedures, for offering deep sedation (DS)/general anesthesia (GA) to all children undergoing lumbar puncture, for the use of DS/GA in major procedures in children of all ages, for the use of hypnosis in all needle procedures and for the use of active distraction in all needle procedures.Conclusion: In this CPG, an evidence-based approach to manage procedure-related pain and distress in children with cancer is presented. As children with cancer often undergo repeated needle procedures during treatment, prevention and alleviation of procedure-related pain and distress is of the utmost importance to increase quality of life in these children and their families.
|
|
| 10. |
- McEvoy, Peter M., et al.
(författare)
-
Imagery-enhanced v. verbally-based group cognitive behavior therapy for social anxiety disorder : a randomized clinical trial
- 2022
-
Ingår i: Psychological Medicine. - : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 52:7, s. 1277-1286
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundCognitive behavior therapy (CBT) is effective for most patients with a social anxiety disorder (SAD) but a substantial proportion fails to remit. Experimental and clinical research suggests that enhancing CBT using imagery-based techniques could improve outcomes. It was hypothesized that imagery-enhanced CBT (IE-CBT) would be superior to verbally-based CBT (VB-CBT) on pre-registered outcomes.MethodsA randomized controlled trial of IE-CBT v. VB-CBT for social anxiety was completed in a community mental health clinic setting. Participants were randomized to IE (n = 53) or VB (n = 54) CBT, with 1-month (primary end point) and 6-month follow-up assessments. Participants completed 12, 2-hour, weekly sessions of IE-CBT or VB-CBT plus 1-month follow-up.ResultsIntention to treat analyses showed very large within-treatment effect sizes on the social interaction anxiety at all time points (ds = 2.09-2.62), with no between-treatment differences on this outcome or clinician-rated severity [1-month OR = 1.45 (0.45, 4.62), p = 0.53; 6-month OR = 1.31 (0.42, 4.08), p = 0.65], SAD remission (1-month: IE = 61.04%, VB = 55.09%, p = 0.59); 6-month: IE = 58.73%, VB = 61.89%, p = 0.77), or secondary outcomes. Three adverse events were noted (substance abuse, n = 1 in IE-CBT; temporary increase in suicide risk, n = 1 in each condition, with one being withdrawn at 1-month follow-up).ConclusionsGroup IE-CBT and VB-CBT were safe and there were no significant differences in outcomes. Both treatments were associated with very large within-group effect sizes and the majority of patients remitted following treatment.
|
|
