10 documents found, page 1 of 1
Improving genetic prediction by leveraging genetic correlations among human dis...
Maier, Robert M.; Zhu, Zhihong; Lee, Sang Hong; Trzaskowski, Maciej; Ruderfer, Douglas M.; Stahl, Eli A.; Ripke, Stephan; Wray, Naomi R.; Yang, JianGenomic prediction has the potential to contribute to precision medicine. However, to date, the utility of such predictors is limited due to low accuracy for most traits. Here theory and simulation study are used to demonstrate that widespread pleiotropy among phenotypes can be utilised to improve genomic risk prediction. We show how a genetic predictor can be created as a weighted index that combines published...
Association Study of 83 Candidate Genes for Bipolar Disorder in Chromosome 6q S...
Bigdeli, Bernard; Maher, Brion S.; Zhao, Zhongming; Sun, Jingchun; Medeiros, Helena; Akula, Nirmala; McMahon, Francis J.; Carvalho, CéliaBackground: Prior genome-scans of bipolar disorder have revealed chromosome 6q22 as a promising candidate region. However, linkage disequilibrium (LD) mapping studies have yet to identify replicated susceptibility loci. Methods: We analyzed 1,422 LD-tagging single nucleotide polymorphisms (SNPs) in 83 genes to test single-marker and locus-wide evidence of association with bipolar disorder in the NIMH Genetics I...
Genetic Overlap of Schizophrenia and Bipolar Disorder in a High-Density Linkage...
Fanous, Ayman H.; Middleton, Frank A.; Gentile, Karen; Amdur, Richard L.; Maher, Brion S.; Zhao, Zhongming; Sun, Jingchun; Medeiros, HelenaRecent family and genome-wide association studies strongly suggest shared genetic risk factors for schizophrenia (SZ) and bipolar disorder (BP). However, linkage studies have not been used to test for statistically significant genome-wide overlap between them. Forty-seven Portuguese families with sibpairs concordant for SZ, BP, or psychosis (PSY, which includes either SZ or psychotic BP) were genotyped for over...
Rare chromosomal deletions and duplications increase risk of schizophrenia
Craddock, N. J.; Gill, M.; Hultman, C. M.; Lichtenstein, P.; McQuillin, A.; Pato, Carlos N.; Ruderfer, D. M.; Owen, M. J.; St Clair, DavidSchizophrenia is a severe mental disorder marked by hallucinations, delusions, cognitive deficits and apathy, with a heritability estimated at 73–90% (ref. 1). Inheritance patterns are complex, and the number and type of genetic variants involved are not understood. Copy number variants (CNVs) have been identified in individual patients with schizophrenia and also in neurodevelopmental disorders, but large-scal...
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...
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...
A linkage study between the GABAA beta2 and GABAA gamma2 subunit genes and majo...
Ambrósio, Alda M.; Kennedy, James L.; Macciardi, Fabio; King, Nicole; Azevedo, Maria H.; Oliveira, Catarina R.; Pato, Carlos N.Background: Alterations of the γ-aminobutyric acid (GABA) system have been implicated in the pathophysiology of major psychoses. Objective: Restriction fragment length polymorphisms associated with the human γ-aminobutyric acid type A (GABAA) β2 and GABAA γ2 subunit genes on chromosome 5q32-q35 were tested to determine whether they confer susceptibility to major psychoses. Methods: Thirty-two schizophrenic fami...
Genome-wide scan in Portuguese Island families identifies 5q31-5q35 as a suscep...
Sklar, P.; Pato, Michele T.; Kirby, A. N.; Petryshen, T. L.; Medeiros, Helena; Carvalho, Célia; Macedo, António; Dourado, A.; Coelho, I.; Valente, J.Schizophrenia is a common psychiatric disorder with a complex genetic etiology. To understand the genetic basis of this syndrome in Portuguese Island populations, we performed a genome-wide scan of 29 families with schizophrenia, which identified a single region on 5q31-5q35 with strong linkage (NPL=3.09, P=0.0012 at D5S820). Empirical simulations set a genome-wide threshold of NPL=3.10 for significant linkage....
Genome-wide scan in Portuguese Island families implicates multiple loci in bipo...
Pato, Carlos N.; Pato, Michele T.; Kirby, A. N.; Petryshen, T. L.; Medeiros, Helena; Carvalho, Célia; Macedo, António; Dourado, A.; Coelho, I.As part of an extensive study in the Portuguese Island population of families with multiple patients suffering from bipolar disorder and schizophrenia, we performed an initial genome-wide scan of 16 extended families with bipolar disorder that identified three regions on chromosomes 2, 11, and 19 with genome-wide suggestive linkage and several other regions, including chromosome 6q, also approached suggestive l...
Genomewide Linkage Analysis of Bipolar Disorder by Use of a High Density Single...
Middleton, Frank A.; Pato, Michele T.; Gentile, Karen; Morley, C. P.; Zhao, X.; Eisener, A. F.; Brown, A.; Petryshen, T. L.; Kirby, A. N.We performed a linkage analysis on 25 extended multiplex Portuguese families segregating for bipolar disorder, by use of a high-density single-nucleotide-polymorphism (SNP) genotyping assay, the GeneChip Human Mapping 10K Array (HMA10K). Of these families, 12 were used for a direct comparison of the HMA10K with the traditional 10-cM microsatellite marker set and the more dense 4-cM marker set. This comparative ...