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The question of what significance threshold is appropriate for genomewide association studies is somewhat unresolved. Previous theoretical suggestions have yet to be validated in practice, whereas permutation testing does not resolve a discrepancy between the genomewide multiplicity of the experiment and the subset of markers actually tested. We used(More)
Schizophrenia, a devastating psychiatric disorder, has a prevalence of 0.5-1%, with high heritability (80-85%) and complex transmission. Recent studies implicate rare, large, high-penetrance copy number variants in some cases, but the genes or biological mechanisms that underlie susceptibility are not known. Here we show that schizophrenia is significantly(More)
Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major(More)
Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067(More)
BACKGROUND There is increasing evidence for genetic effects on the hypothalamic-pituitary axis system. More than one gene is likely to moderate corticoid-mediated activity. AIMS To investigate whether the brain-derived neurotrophic factor (BDNF) polymorphism (rs6265, Val66Met) is associated with morning waking salivary cortisol and moderates the(More)
BACKGROUND This paper describes an automated method for finding clusters of interconnected proteins in protein interaction networks and retrieving protein annotations associated with these clusters. RESULTS Protein interaction graphs were separated into subgraphs of interconnected proteins, using the JUNG implementation of Girvan and Newman's(More)
Hematopoiesis is a carefully controlled process that is regulated by complex networks of transcription factors that are, in part, controlled by signals resulting from ligand binding to cell-surface receptors. To further understand hematopoiesis, we have compared gene expression profiles of human erythroblasts, megakaryocytes, B cells, cytotoxic and helper T(More)
Large exploratory studies, including candidate-gene-association testing, genomewide linkage-disequilibrium scans, and array-expression experiments, are becoming increasingly common. A serious problem for such studies is that statistical power is compromised by the need to control the false-positive rate for a large family of tests. Because multiple true(More)
Large exploratory studies are often characterized by a preponderance of true null hypotheses, with a small though multiple number of false hypotheses. Traditional multiple-test adjustments consider either each hypothesis separately, or all hypotheses simultaneously, but it may be more desirable to consider the combined evidence for subsets of hypotheses, in(More)