10 documents found, page 1 of 1
Analysis of shared heritability in common disorders of the brain
Anttila, Verneri; Bulik-Sullivan, Brendan; Finucane, Hilary K.; Walters, Raymond K.; Bras, Jose; Duncan, Laramie; Escott-Price, ValentinaDisorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common varian...
Reassessing the Evolutionary History of the 17q21 Inversion Polymorphism
Alves, Joao M; Lima, Ana C; Pais, Isa A; Amir, Nadir; Celestino, Ricardo; Piras, Giovanna; Monne, Maria; Comas, David; Heutink, Peter; Chikhi, LounèsA polymorphic inversion that lies on chromosome 17q21 comprises two major haplotype families (H1 and H2) that not only differ in orientation but also in copy-number. Although the processes driving the spread of the inversion-associated lineage (H2) in humans remain unclear, a selective advantage has been proposed for one of its subtypes. Here, we genotyped a large panel of individuals from previously overlooked...
Dominant negative effect of polyglutamine expansion perturbs normal function of...
Carvalho, Andreia Alexandra Neves; Logarinho, Elsa; Freitas, Ana; Silva, Sara Duarte; Costa, Maria do Carmo; Fernandes, Anabela SilvaThe physiological function of Ataxin-3 (ATXN3), a deubiquitylase (DUB) involved in Machado–Joseph Disease (MJD), remains elusive. In this study, we demonstrate that ATXN3 is required for neuronal differentiation and for normal cell morphology, cytoskeletal organization, proliferation and survival of SH-SY5Y and PC12 cells. This cellular phenotype is associated with increased proteasomal degradation of a5 integr...
Reassessing the Evolutionary History of the 17q21 Inversion Polymorphism
Alves, Joao M.; Lima, Ana C.; Pais, Isa A.; Amir, Nadir; Celestino, Ricardo; Piras, Giovanna; Monne, Maria; Comas, David; Heutink, Peter; Chikhi, LounèsA polymorphic inversion that lies on chromosome 17q21 comprises two major haplotype families (H1 and H2) that not only differ in orientation but also in copy-number. Although the processes driving the spread of the inversion-associated lineage (H2) in humans remain unclear, a selective advantage has been proposed for one of its subtypes. Here, we genotyped a large panel of individuals from previously overlooked...
The rs5743836 polymorphism in TLR9 confers a population-based increased risk of...
Carvalho, Agostinho; Cunha, Cristina; Almeida, A. J.; Osório, Nuno S.; Saraiva, Margarida; Coelho, Maria Teixeira; Pedreiro, Susana; Torrado, EgídioNon-Hodgkin lymphoma (NHL) has been associated with immunological defects, chronic inflammatory and autoimmune conditions. Given the link between immune dysfunction and NHL, genetic variants in toll-like receptors (TLRs) have been regarded as potential predictive factors of susceptibility to NHL. Adequate anti-tumoral responses are known to depend on TLR9 function, such that the use of its synthetic ligand is b...
Ubiquitin associated protein 1 is a risk factor for frontotemporal lobar degene...
Rollinson, Sara; Rizzu, Patrizia; Sikkink, Stephen; Baker, Matthew; Halliwell, Nicola; Snowden, Julie; Traynor, Bryan J.; Ruano, Dina; Cairns, Nigelhttp://www.sciencedirect.com/science/article/B6T09-4VKMW0R-1/2/c38ac7e3dcb87f1e42d35a151a3f69b2
Transthyretin: No association between serum levels or gene variants and schizop...
Ruano, Dina; Macedo, António; Soares, Maria J.; Valente, José; Azevedo, Maria H.; Hutz, Mara H.; Gama, Clarissa S.; Lobato, Maria I.It has been proposed that schizophrenia results from an environmental insult in genetically predisposed individuals. Environmental factors capable of modulating transcriptional activity and their carriers could link the genetic and environmental components of schizophrenia. Among these is transthyretin (TTR), a major carrier of thyroid hormones and retinol-binding protein (RBP). Retinoids and thyroid hormones r...
Family-based and case-control studies reveal no association of lipocalin-type p...
Ruano, Dina; Macedo, António; Soares, Maria João; Valente, José; Azevedo, Maria Helena; Pato, Carlos; Hutz, Mara Helena; Gama, Clarissa S.Several observations point to the involvement of disturbed lipid biology in schizophrenia. Reduced response to niacin flushing test, which involves vasodilatation induced by prostaglandin D2 (PGD2), is among the evidences, together with decreased CSF levels of lipocalin-type prostaglandin D2 synthase (PTGDS), the enzyme responsible for the synthesis of PGD2 in the brain. Since PTGDS is also a carrier for lipoph...
Transthyretin: no association between serum levels or gene variants and schizop...
Ruano, Dina; Macedo, António; Soares, Maria J.; Valente, José; Azevedo, Maria H.; Hutz, Mara H.; Gama, Clarissa S.; Lobato, Maria I.It has been proposed that schizophrenia results from an environmental insult in genetically predisposed individuals. Environmental factors capable of modulating transcriptional activity and their carriers could link the genetic and environmental components of schizophrenia. Among these is transthyretin (TTR), a major carrier of thyroid hormones and retinol-binding protein (RBP). Retinoids and thyroid hormones r...
Linkage disequilibrium and haplotype homozygosity in population samples genotyp...
Wang, Hui; Lin, Chia-Ho; Service, Susan; Chen, Yuguo; Freimer, Nelson; Sabatti, Chiara; Karayiorgou, Maria; Roos, J. Louw; Pretorious, HermanObjective: Analyze the information contained in homozygous haplotypes detected with high density genotyping. Methods: We analyze the genotypes of ∼2,500 markers on chr 22 in 12 population samples, each including 200 individuals. We develop a measure of disequilibrium based on haplotype homozygosity and an algorithm to identify genomic segments characterized by non-random homozygosity (NRH), taking into account ...