| 1. |
- Bejerot, Susanne, 1955-, et al.
(författare)
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Evidence-Based Brief Obsessive-Compulsive Scale
- 2017
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Ingår i: Journal of Central Nervous System Disease. - : Sage Publications. - 1179-5735. ; 9
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 2. |
- Frisén, Louise
(författare)
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Genetic studies of hypospadias
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hypospadias is defined as an abnormal opening of the urethra on the underside of the penis. It is a frequently found malformation with an incidence of 3 per 1000 males. The aim of this thesis was to identify genetic and environmental factors in the pathogenesis of hypospadias. For this purpose, a variety of genetic methods were used in a nation-wide material corresponding to half of all registered cases of hypospadias in Sweden. We identified 18 monozygotic twins discordant for hypospadias. In 16 of these, the twin with lowest birth weight was affected with hypospadias. This shows that low birth weight is important for hypospadias, regardless of the genetic constitution (paper 1). We investigated the familial rate and analyzed the association with low birth weight in 2138 families with at least one boy with hypospadias. There was a familial rate of 7% and a significant lower birth weight in cases with hypospadias compared with their respective brothers, used as controls (p=5x10-13). An increased frequency of dizygotic as well as monozygotic male-male twins was found, with a skewed distribution towards monozygotic twins. This paper (II) also includes a description of the ethnic background in the material and the distribution of phenotypes. A complex segregation analysis was performed to define the mode of inheritance in a material consisting of 2005 pedigrees. We found a best fit for the multifactorial model and a heritability of 0.99. This is interpreted as monogenic effects acting in some of the families but a multifactorial cause in the majority (paper III). A genome-wide linkage analysis based on a non-parametric affected relative pair method was used in 69 families. All available family members were genotyped with 360 polymorphic PCR based microsatellite markers with a mean interval of 9.5 cM. Five chromosomal regions reaching the level of suggestive significance were identified (paper IV). These need to be investigated further to identify hypospadias susceptibility genes. Linkage analysis and subsequent mutation analysis in a family with autosomal dominant inheritance of hypospadias revealed a novel mutation in the HOXA13 gene (paper V). This suggests the diagnosis of hand-foot-genital syndrome although the phenotype in this family is atypical compared with previously reported families. In this thesis, several lines of evidence suggesting genetic factors in the pathogenesis of hypospadias are presented, including the identification of five chromosomal regions in which genes for hypospadias are likely to be located and a novel mutation in the HOXA13 gene. It is also shown that low birth weight is an important risk factor for hypospadias.
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| 3. |
- Herrera-Rivero, Marisol, et al.
(författare)
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Exploring the genetics of lithium response in bipolar disorders.
- 2023
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Ingår i: Research square.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N=2,064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II.We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism.Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.
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| 4. |
- Herrera-Rivero, Marisol, et al.
(författare)
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Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder.
- 2023
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Ingår i: Research square.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The link between bipolar disorder (BP) and immune dysfunction remains controversial. While epidemiological studies have long suggested an association, recent research has found only limited evidence of such a relationship. To clarify this, we investigated the contributions of immune-relevant genetic factors to the response to lithium (Li) treatment and the clinical presentation of BP. First, we assessed the association of a large collection of immune-related genes (4,925) with Li response, defined by the Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale), and clinical characteristics in patients with BP from the International Consortium on Lithium Genetics (ConLi+Gen, N = 2,374). Second, we calculated here previously published polygenic scores (PGSs) for immune-related traits and evaluated their associations with Li response and clinical features. We found several genes associated with Li response at p < 1×10- 4 values, including HAS3, CNTNAP5 and NFIB. Network and functional enrichment analyses uncovered an overrepresentation of pathways involved in cell adhesion and intercellular communication, which appear to converge on the well-known Li-induced inhibition of GSK-3β. We also found various genes associated with BP's age-at-onset, number of mood episodes, and presence of psychosis, substance abuse and/or suicidal ideation at the exploratory threshold. These included RTN4, XKR4, NRXN1, NRG1/3 and GRK5. Additionally, PGS analyses suggested serum FAS, ECP, TRANCE and cytokine ligands, amongst others, might represent potential circulating biomarkers of Li response and clinical presentation. Taken together, our results support the notion of a relatively weak association between immunity and clinically relevant features of BP at the genetic level.
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| 5. |
- Kelsoe, John, et al.
(författare)
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Lithium Response in Bipolar Disorder is Associated with Focal Adhesion and PI3K-Akt Networks: A Multi-omics Replication Study.
- 2023
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Ingår i: Research square.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2,039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.
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