| 1. |
- Frazier-Wood, Alexis C., et al.
(författare)
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Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
- 2016
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Ingår i: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
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Tidskriftsartikel (refereegranskat)abstract
- Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
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| 2. |
- Brusewitz, Göran, et al.
(författare)
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Exceptional experiences amongst twins
- 2013
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Ingår i: Journal of the Society for psychical research. - 0037-9751. ; 77:913, s. 220-235
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Tidskriftsartikel (refereegranskat)abstract
- Two studies are reported here concerning the relationship between exceptional experiences in pairs of twins and their degree of attachment to each other. The initial study collated replies to a questionnaire given to a large number of twins who were attending a Twin-Day celebration. The further study used a highly selected series of replies from a postal survey of the twins in the Twin Registry. Both studies used the Exceptional Experiences Questionnaire, which recorded the frequency of remarkable coincidences, shared dreams and apparent telepathy, as well as the degree and duration of the attachments the twins experienced to each other. In the survey study, 60% of the responding twins reported having experienced events that they judged to be of a telepathic nature. Frequent telepathic experiences were reported by 11% and remarkable coincidences by 56% of the respondents. Identical twins reported having these experiences significantly more often and having a significantly stronger attachment to each other than was the case for non- identical twins. A significant relationship was also found to occur between reporting a strong attachment and reporting many and more remarkable exceptional experiences. A large majority of the twins reported these experiences as having occurred in a waking state. Almost half of the twins reported the experience of telepathy to raise concern for the welfare of the other twin, often relating to a pain or illness, or injury. However, in the postal survey group about one third of the remarkable events were positive events. The use of a private language and the occurrence of shared dreams seem to be further hallmarks of these experiences.
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| 3. |
- Harris, Anna E., et al.
(författare)
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Exploring anti-androgen therapies in hormone dependent prostate cancer and new therapeutic routes for castration resistant prostate cancer
- 2022
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media S.A.. - 1664-2392. ; 13
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Forskningsöversikt (refereegranskat)abstract
- Androgen deprivation therapies (ADTs) are important treatments which inhibit androgen-induced prostate cancer (PCa) progression by either preventing androgen biosynthesis (e.g. abiraterone) or by antagonizing androgen receptor (AR) function (e.g. bicalutamide, enzalutamide, darolutamide). A major limitation of current ADTs is they often remain effective for limited durations after which patients commonly progress to a lethal and incurable form of PCa, called castration-resistant prostate cancer (CRPC) where the AR continues to orchestrate pro-oncogenic signalling. Indeed, the increasing numbers of ADT-related treatment-emergent neuroendocrine-like prostate cancers (NePC), which lack AR and are thus insensitive to ADT, represents a major therapeutic challenge. There is therefore an urgent need to better understand the mechanisms of AR action in hormone dependent disease and the progression to CRPC, to enable the development of new approaches to prevent, reverse or delay ADT-resistance. Interestingly the AR regulates distinct transcriptional networks in hormone dependent and CRPC, and this appears to be related to the aberrant function of key AR-epigenetic coregulator enzymes including the lysine demethylase 1 (LSD1/KDM1A). In this review we summarize the current best status of anti-androgen clinical trials, the potential for novel combination therapies and we explore recent advances in the development of novel epigenetic targeted therapies that may be relevant to prevent or reverse disease progression in patients with advanced CRPC.
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| 4. |
- Margolis, Russell L, et al.
(författare)
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Huntington's Disease-like 2 (HDL2) in North America and Japan.
- 2004
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 56:5, s. 670-4
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Tidskriftsartikel (refereegranskat)abstract
- Huntington's Disease-like 2 (HDL2) is a progressive, autosomal dominant, neurodegenerative disorder with marked clinical and pathological similarities to Huntington's disease (HD). The causal mutation is a CTG/CAG expansion mutation on chromosome 16q24.3, in a variably spliced exon of junctophilin-3. The frequency of HDL2 was determined in nine independent series of patients referred for HD testing or selected for the presence of an HD-like phenotype in North America or Japan. The repeat length, ancestry, and age of onset of all North American HDL2 cases were determined. The results show that HDL2 is very rare, with a frequency of 0 to 15% among patients in the nine case series with an HD-like presentation who do not have the HD mutation. HDL2 is predominantly, and perhaps exclusively, found in individuals of African ancestry. Repeat expansions ranged from 44 to 57 triplets, with length instability in maternal transmission detected in a repeat of r2=0.29, p=0.0098). The results further support the evidence that the repeat expansion at the chromosome 16q24.3 locus is the direct cause of HDL2 and provide preliminary guidelines for the genetic testing of patients with an HD-like phenotype.
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