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Functional variations modulating PRKCA expression and alternative splicing predispose to multiple sclerosis

The protein kinase C alpha (PRKCA) gene, encoding a Th17-cell-selective kinase, was repeatedly associated with multiple sclerosis (MS), but the underlying pathogenic mechanism remains unknown. We replicated the association in Italians (409 cases, 723 controls), identifying a protective signal in the PRKCA promoter (P = 0.033), and a risk haplotype in intron 3 (P = 7.7 × 10−4...

Discovery Properties of Genome-wide Association Signals From Cumulatively Combined Data Sets

A. Patsopoulos, Georgia Salanti, John P. A. Ioannidis); Biomedical Research Institute, Foundation for Research and Technology—Hellas, Ioannina, Greece (John P. A. Ioannidis); and Tufts Clinical and ... Paulo, Brazil (Tiago V. Pereira); Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece (Tiago V. Pereira, Nikolaos

Selection and Presentation of Imaging Figures in the Medical Literature

Background Images are important for conveying information, but there is no empirical evidence on whether imaging figures are properly selected and presented in the published medical literature. We therefore evaluated the selection and presentation of radiological imaging figures in major medical journals. Methodology/Principal Findings We analyzed articles published in 2005 in 12...

Heterogeneity in Meta-Analyses of Genome-Wide Association Investigations

BackgroundMeta-analysis is the systematic and quantitative synthesis of effect sizes and the exploration of their diversity across different studies. Meta-analyses are increasingly applied to synthesize data from genome-wide association (GWA) studies and from other teams that try to replicate the genetic variants that emerge from such investigations. Between-study heterogeneity...

Fine-Mapping the Genetic Association of the Major Histocompatibility Complex in Multiple Sclerosis: HLA and Non-HLA Effects

The major histocompatibility complex (MHC) region is strongly associated with multiple sclerosis (MS) susceptibility. HLA-DRB1*15:01 has the strongest effect, and several other alleles have been reported at different levels of validation. Using SNP data from genome-wide studies, we imputed and tested classical alleles and amino acid polymorphisms in 8 classical human leukocyte...

Fine-mapping classical HLA variation associated with durable host control of HIV-1 infection in African Americans

Amy C. Weintrob 10 Nikolaos A. Patsopoulos 6 8 13 Xiaoming Jia 15 Rachel L. Erlich 13 Niall J. Lennon 13 Carl M. Kadie 14 David Heckerman 9 Namrata Gupta 13 David W. Haas 4 Steven G. Deeks 5 Florencia

International ranking systems for universities and institutions: a critical appraisal

Background Ranking of universities and institutions has attracted wide attention recently. Several systems have been proposed that attempt to rank academic institutions worldwide. Methods We review the two most publicly visible ranking systems, the Shanghai Jiao Tong University 'Academic Ranking of World Universities' and the Times Higher Education Supplement 'World University...

Reporting of Human Genome Epidemiology (HuGE) association studies: An empirical assessment

Background Several thousand human genome epidemiology association studies are published every year investigating the relationship between common genetic variants and diverse phenotypes. Transparent reporting of study methods and results allows readers to better assess the validity of study findings. Here, we document reporting practices of human genome epidemiology studies...