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- Reinbold, C. S., et al.
(författare)
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Analysis of the Influence of microRNAs in Lithium Response in Bipolar Disorder
- 2018
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Ingår i: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) is a common, highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. Lithium is the best-established long-term treatment for BD, even though individual response is highly variable Evidence suggests that some of this variability has a genetic basis. This is supported by the largest genome-wide association study (GWAS) of lithium response to date conducted by the International Consortium on Lithium Genetics (ConLiGen) Recently, we performed the first genome-wide analysis of the involvement of miRNAs in BD and identified nine BD associated miRNAs However, it is unknown whether these miRNAs are also associated with lithium response in BD. In the present study, we therefore tested whether common variants at these nine candidate miRNAs contribute to the variance in lithium response in BD. Furthermore, we systematically analyzed whether any other miRNA in the genome is implicated in the response to lithium. For this purpose, we performed gene-based tests for all known miRNA coding genes in the ConLiGen GWAS dataset (n = 2,563 patients) using a set-based testing approach adapted from the versatile gene based test for GWAS (VEGAS2). In the candidate approach, miR-499a showed a nominally significant association with lithium response, providing some evidence for involvement in both development and treatment of BD. In the genome-wide miRNA analysis, 71 miRNAs showed nominally significant associations with the dichotomous phenotype and 106 with the continuous trait for treatment response. A total of 15 miRNAs revealed nominal significance in both phenotypes with miR-633 showing the strongest association with the continuous trait (p = 9.80E-04) and miR-607 with the dichotomous phenotype (p = 5.79E-04). No association between miRNAs and treatment response to lithium in BD in either of the tested conditions withstood multiple testing correction. Given the limited power of our study, the investigation of miRNAs in larger GWAS samples of BD and lithium response is warranted.
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- de Jong, S, et al.
(författare)
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Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
- 2018
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 1, s. 163-
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Tidskriftsartikel (refereegranskat)abstract
- Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.
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- Holmqvist Gattario, Kristina, 1981, et al.
(författare)
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How Is Men's Conformity to Masculine Norms Related to Their Body Image? Masculinity and Muscularity Across Western Countries
- 2015
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Ingår i: Psychology of Men & Masculinity. - : American Psychological Association (APA). - 1524-9220 .- 1939-151X. ; 16:3, s. 337-347
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Tidskriftsartikel (refereegranskat)abstract
- Previous research has suggested that men's conformity to masculine norms (CMN) is an important correlate of men's drive for muscularity. The present study aimed to further delineate the relationship between masculinity and men's body image by examining various dimensions of CMN in relation to various dimensions of men's body image (muscularity, leanness, and fitness) in a cross-national sample. Participants comprised young men from the United States (n = 192), the United Kingdom (n = 141), Australia (n = 160), and Sweden (n = 142). Multigroup path analyses showed that CMN was related to drive for muscularity, leanness, and fitness in all 4 countries, but there were differences across countries in which dimensions of CMN predicted men's body image. Whereas conformity to the masculine norm of winning was a salient predictor across the 4 countries, conformity to the norm of risk-taking was linked to Australian men's body image, and conformity to the norm of violence to British men's body image. The findings support previous research suggesting that men's endorsement of the male gender role plays a significant role in their desire for an ideal body, but the results uniquely document that this relationship may differ across countries.
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- Kalman, Janos L, et al.
(författare)
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Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study.
- 2019
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Ingår i: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 21:1, s. 68-75
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients.A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18 years] vs adulthood [>18 years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models.BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment.The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.
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- De Jesus, A. Y., et al.
(författare)
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Media internalization and conformity to traditional masculine norms in relation to body image concerns among men
- 2015
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Ingår i: Eating Behaviors. - : Elsevier BV. - 1471-0153. ; 18, s. 137-142
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have separately examined conformity tomasculine norms and internalization of body ideals in themedia in relation to the drive formuscularity (DM). This study was designed to examine these factors together in relation toDM, and further examine howtheymay differ in relation to drive for thinness (DT) and drive for leanness (DL). Participants were 284 Australian males between ages 18 and 42. They completed validated measures that assessed DM, DT, DL, male gender role norms, and internalization of body ideals. The findings showed that internalization of body ideals mediated the relationship between masculine role norms and body image in the case of both DM and DL. However, masculine norms and internalization were independent predictors of DT. Our findings contribute to further understanding of the roles that the media and masculine norms have in shaping men's drive for muscularity, leanness, and thinness. Longitudinal research is needed to confirm the nature and direction of these relationships. (C) 2015 Elsevier Ltd. All rights reserved.
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