| 1. |
- Amare, Azmeraw, et al.
(författare)
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Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder.
- 2023
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Ingår i: Research square. - : Research Square Platform LLC.
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2,367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������.
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| 2. |
- Amare, Azmeraw T, et al.
(författare)
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Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.
- 2023
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Ingår i: Molecular psychiatry. - 1476-5578. ; 28, s. 5251-5261
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental healthdisorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P=9.8×10-12, R2=1.9%) and continuous (P=6.4×10-9, R2=2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P=3.9×10-4, R2=0.9%), but not for the continuous outcome (P=0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
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| 3. |
- Laurie, Steven, et al.
(författare)
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The RD-Connect Genome-Phenome Analysis Platform : Accelerating diagnosis, research, and gene discovery for rare diseases
- 2022
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Ingår i: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 43:6, s. 717-733
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Tidskriftsartikel (refereegranskat)abstract
- Rare disease patients are more likely to receive a rapid molecular diagnosis nowadays thanks to the wide adoption of next-generation sequencing. However, many cases remain undiagnosed even after exome or genome analysis, because the methods used missed the molecular cause in a known gene, or a novel causative gene could not be identified and/or confirmed. To address these challenges, the RD-Connect Genome-Phenome Analysis Platform (GPAP) facilitates the collation, discovery, sharing, and analysis of standardized genome-phenome data within a collaborative environment. Authorized clinicians and researchers submit pseudonymised phenotypic profiles encoded using the Human Phenotype Ontology, and raw genomic data which is processed through a standardized pipeline. After an optional embargo period, the data are shared with other platform users, with the objective that similar cases in the system and queries from peers may help diagnose the case. Additionally, the platform enables bidirectional discovery of similar cases in other databases from the Matchmaker Exchange network. To facilitate genome-phenome analysis and interpretation by clinical researchers, the RD-Connect GPAP provides a powerful user-friendly interface and leverages tens of information sources. As a result, the resource has already helped diagnose hundreds of rare disease patients and discover new disease causing genes.
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| 4. |
- Thielmann, Isabel, et al.
(författare)
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The HEXACO-100 Across 16 Languages : A Large-Scale Test of Measurement Invariance
- 2020
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Ingår i: Journal of Personality Assessment. - : Informa UK Limited. - 0022-3891 .- 1532-7752. ; 102:5, s. 714-726
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Tidskriftsartikel (refereegranskat)abstract
- The HEXACO Personality Inventory-Revised (HEXACO-PI-R) has become one of the most heavily applied measurement tools for the assessment of basic personality traits. Correspondingly, the inventory has been translated to many languages for use in cross-cultural research. However, formal tests examining whether the different language versions of the HEXACO-PI-R provide equivalent measures of the 6 personality dimensions are missing. We provide a large-scale test of measurement invariance of the 100-item version of the HEXACO-PI-R across 16 languages spoken in European and Asian countries (N = 30,484). Multigroup exploratory structural equation modeling and confirmatory factor analyses revealed consistent support for configural and metric invariance, thus implying that the factor structure of the HEXACO dimensions as well as the meaning of the latent HEXACO factors is comparable across languages. However, analyses did not show overall support for scalar invariance; that is, equivalence of facet intercepts. A complementary alignment analysis supported this pattern, but also revealed substantial heterogeneity in the level of (non)invariance across facets and factors. Overall, results imply that the HEXACO-PI-R provides largely comparable measurement of the HEXACO dimensions, although the lack of scalar invariance highlights the necessity for future research clarifying the interpretation of mean-level trait differences across countries.
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| 5. |
- Trevisan, Caterina, et al.
(författare)
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Falls may trigger body weight decline in nursing home residents
- 2021
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Ingår i: Nutrition (Burbank, Los Angeles County, Calif.). - : Elsevier BV. - 0899-9007 .- 1873-1244. ; 90
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The effect of falls on changes in body weight is still unknown. This study investigated the extent to which falls can modify the course of body weight in nursing home residents, and aimed to identify the factors that might modulate this effect.Methods: The sample included 132 residents aged ≥60 y who had experienced at least one fall after nursing home admission. Body weight was measured monthly in the 6 mo after the fall in the entire sample, and also in the 6 mo prefall in a subsample (n = 111). Sociodemographic and health data were obtained from medical records. Linear mixed models were used to estimate the average monthly changes in body weight after the fall in the total sample, and as a function of the sociodemographic and medical factors.Results: Falls modified the course of body weight in the total sample (β = −0.28, 95% confidence interval, −0.44 to −0.12, for the change in slope before and after fall) in all age classes and especially in individuals with severe cognitive impairment who received less-frequent informal visits (β = −0.55, 95% confidence interval, −0.87 to −0.22). Individuals aged ≥90 y and those with severe cognitive impairment had a steeper monthly weight decline in the 6 mo postfall, of 0.23 and 0.35 kg greater, respectively, than their younger and cognitively healthier counterparts.Conclusions: Falls may trigger a body weight loss in nursing home residents, especially in the oldest old people and those with severe cognitive impairment who receive little support from informal caregivers. These findings highlight the importance of monitoring nutritional status of people who live in institutions after falls.
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