| 21. |
- Falhammar, Henrik, et al.
(författare)
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Increased psychiatric morbidity in men with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
- 2014
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 99:3
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Tidskriftsartikel (refereegranskat)abstract
- Context:Reports on psychiatric morbidity in males with congenital adrenal hyperplasia (CAH) are lacking.Objective:To study psychiatric disorders in CAH males.Design, Setting and Participants:We studied males with CAH (21-hydroxylase deficiency, n=253; CYP21A2 mutations known, n=185), and compared them with controls (n=25300). Data were derived through linkage of national population-based registers. We assessed the subgroups of CYP21A2 genotype separately (null, I2splice, I172N, P30L and NC), as well as outcomes before and after the introduction of national neonatal screening in 1986.Main Outcome Measures:Psychiatric disorders including attempted and completed suicide (suicidality).Results:Psychiatric disorders (suicidality not included), suicidality and alcohol misuse were increased in CAH males compared with controls (OR 1.5, 2.3, and 1.9; 95%CI 1.1-2.2, 1.1-5.0, and 1.0-3.5). In the null genotype group, no increased rates were seen; in the I2splice group, psychiatric disorders, personality disorders and alcohol misuse were increased; in the I172N group suicide attempt and drug misuse were increased; and in the P30L and NC group psychotic disorders were increased. In CAH males born before the neonatal screening, the rate of psychiatric disorders and suicidality were increased, but only psychotic disorders in those born after. There was no increased risk for any neurodevelopmental disorder.Conclusions:CAH males have an increased psychiatric morbidity. Psychiatric morbidity was not raised in the most severe genotype group. Late diagnosis of CAH may explain some of the findings. Those born before the introduction of neonatal screening were more affected, which may be explained by the higher age.
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| 22. |
- 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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| 23. |
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| 24. |
- Gotby, A. O., et al.
(författare)
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Congenital Adrenal Hyperplasia, Polycystic Ovary Syndrome and criminal behavior: A Swedish population based study
- 2015
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Ingår i: Psychiatry Research. - : Elsevier BV. - 0165-1781 .- 1872-7123. ; 229:3, s. 953-959
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Tidskriftsartikel (refereegranskat)abstract
- Both prenatal and circulating testosterone and other androgens have been suggested to influence the individual's propensity to commit crime, but empirical evidence is limited and inconsistent. Congenital Adrenal Hyperplasia (CAH) and Polycystic Ovary Syndrome (PCOS) are both hyperandrogenic conditions but with an important difference; whereas subjects with CAH are exposed to high concentrations of androgens in utero, women with PCOS are subjected to high androgens in adulthood. Comparing these groups can therefore yield important insights of androgenic effects on behavior. In the current study, information on medical diagnoses and convicted crimes were gathered from Swedish population-based registers. The associations between diagnoses of CAH or PCOS and any crime, violent crime or sex crime were estimated with conditional logistic regression. Results showed that CAH in women and men did not predict criminality, whereas an increased risk for any crime and violent crime was found in PCOS women. Our findings indicate that female hyperandrogenism in adulthood, but not prenatal hyperandrogenism, is associated with risk for criminal behavior. Further research into hyperandrogenic conditions holds opportunities to deepen our understanding of the etiology of crime and psychopathology. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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| 25. |
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| 26. |
- 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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| 27. |
- 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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| 28. |
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| 29. |
- Hou, Liping, et al.
(författare)
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Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder.
- 2016
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:15, s. 3383-94
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p = 5.87 × 10(-9); odds ratio = 1.12) and markers within ERBB2 (rs2517959, p = 4.53 × 10(-9); odds ratio = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
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| 30. |
- Hukic, Dzana Sudic, et al.
(författare)
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Cognitive Manic Symptoms in Bipolar Disorder Associated with Polymorphisms in the DAOA and COMT Genes
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Introduction:Bipolar disorder is characterized by severe mood symptoms including major depressive and manic episodes. During manic episodes, many patients show cognitive dysfunction. Dopamine and glutamate are important for cognitive processing, thus the COMT and DAOA genes that modulate the expression of these neurotransmitters are of interest for studies of cognitive function.Methodology:Focusing on the most severe episode of mania, a factor was found with the combined symptoms of talkativeness, distractibility, and thought disorder, considered a cognitive manic symptoms (CMS) factor. 488 patients were genotyped, out of which 373 (76%) had talkativeness, 269 (55%) distractibility, and 372 (76%) thought disorder. 215 (44%) patients were positive for all three symptoms, thus showing CMS (Table 1). As population controls, 1,044 anonymous blood donors (ABD) were used. Case-case and case-control design models were used to investigate genetic associations between cognitive manic symptoms in bipolar 1 disorder and SNPs in the COMT and DAOA genes. Results: The finding of this study was that cognitive manic symptoms in patients with bipolar 1 disorder was associated with genetic variants in the DAOA and COMT genes. Nominal association for DAOA SNPs and COMT SNPs to cognitive symptoms factor in bipolar 1 disorder was found in both allelic (Table 2) and haplotypic (Table 3) analyses. Genotypic association analyses also supported our findings. However, only one association, when CMS patients were compared to ABD controls, survived correction for multiple testing by max (T) permutation. Data also suggested interaction between SNPs rs2391191 in DAOA and rs5993883 in COMT in the case-control model. Conclusion:Identifying genes associated with cognitive functioning has clinical implications for assessment of prognosis and progression. Our finding are consistent with other studies showing genetic associations between the COMT and DAOA genes and impaired cognition both in psychiatric disorders and in the general population. © 2013 Hukic et al.
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