12The cerebral cortex underlies our complex cognitive capabilities, yet we know little about the specific genetic loci influencing human cortical structure. To identify genetic variants, including structural variants, impacting cortical structure, we conducted a genome-wide association meta-analysis of brain MRI data from 51,662 individuals. We analysed the surface area and average thickness of the whole cortex and 34 regions with known functional specialisations. We identified 255 nominally significant loci (P ≤ 5 x 10 -8 ); 199 survived multiple testing correction (P ≤ 8.3 x 10 -10 ; 187 surface area; 12 thickness). We found significant enrichment for loci influencing total surface area within regulatory elements active during prenatal cortical development, supporting the radial unit hypothesis. Loci impacting regional surface area cluster near genes in Wnt signalling pathways, known to influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression and ADHD.One Sentence Summary: Common genetic variation is associated with inter-individual variation in the structure of the human cortex, both globally and within specific regions, and is shared with genetic risk factors for some neuropsychiatric disorders.The human cerebral cortex is the outer grey matter layer of the brain, which is implicated in multiple aspects of higher cognitive function. Its distinct folding pattern is characterised by convex (gyral) and concave (sulcal) regions. Computational brain mapping approaches use the consistent folding patterns across individual cortices to label brain regions(1). During fetal development excitatory neurons, the predominant neuronal cell-type in the cortex, are generated from neural progenitor cells in the developing germinal zone(2). The radial unit hypothesis(3) posits that the expansion of cortical surface area (SA) is driven by the proliferation of these neural progenitor cells, whereas thickness (TH) is determined by the number of neurogenic divisions. Variation in global and regional measures of cortical SA and TH are associated with neuropsychiatric disorders and psychological traits(4) ( Table S1). Twin and family-based brain imaging studies show that SA and TH measurements are highly heritable and are largely influenced by independent genetic factors(5). Despite extensive studies of genes impacting cortical structure in model organisms (6), our current understanding of genetic variation impacting human cortical size and patterning is limited to rare, highly penetrant variants (7,8). These variants often disrupt cortical development, leading to altered post-natal structure. However, little is known about how common genetic variants impact human cortical SA and TH.To address this, we conducted genome-wide association meta-analyses of cortical SA and TH measures in 51,662 individuals from 60 cohorts from around the world (Tables S2-S4). Cortical measures were extracted from structural brain MRI scan...

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson’s disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.

SUMMARYThe first Provenance Challenge was set up in order to provide a forum for the community to understand the capabilities of different provenance systems and the expressiveness of their provenance representations. To this end, a functional magnetic resonance imaging workflow was defined, which participants had to either simulate or run in order to produce some provenance representation, from which a set of identified queries had to be implemented and executed. Sixteen teams responded to the challenge, and submitted their inputs. In this paper, we present the challenge workflow and queries, and summarize the participants' contributions.

The Wings intelligent workflow system assists scientists with designing computational experiments by automatically tracking constraints and ruling out invalid designs, letting scientists focus on their experiments and goals. experiment describes how selected data sets are to be processed by a series of software components, in what order, and with what parameter configurations. Earth scientists use computational experiments to estimate seismic hazard through simulations of earthquake forecasts.Biologists use computational experiments to analyze gene expression microarray data or molecular interaction networks and pathways. Social scientists analyze large social networks to discover structural regularities based on mining relations among individuals.Designing computational experiments for scientific analysis is a complex process that includes numerous software components, ranging from general-purpose statistics packages to custom algorithm implementations to specific models and codes. Each software component has different requirements on the kinds of data it is designed to process and constraints on the kinds of operations it can perform. In addition, there are many accessible data sets that could be brought to bear in the analysis, including prototypical reference data sets and large shared repositories. Each data set has metadata attributes that describe data properties that might need to be accounted for in the analysis, including characteristics of the original collection process (such as instrument setups) and any subsequent preprocessing and cleansing (such as normalizing or discretizing). These metadata attributes determine what kinds of components are appropriate for processing. A given component S cientists use computational experiments to study natural phenomena through the lens of software tools and computer programs. 1 These software tools can be configured with diverse settings and parameters, enabling scientists to explore different aspects of the phenomenon at hand. A computational

SUMMARYOur research focuses on creating and executing large-scale scientific workflows that often involve thousands of computations over distributed, shared resources. We describe an approach to workflow creation and refinement that uses semantic representations to (1) describe complex scientific applications in a dataindependent manner, (2) automatically generate workflows of computations for given data sets, and (3) map the workflows to available computing resources for efficient execution. Our approach is implemented in the Wings/Pegasus workflow system and has been demonstrated in a variety of scientific application domains. This paper illustrates the application-level provenance information generated Wings during workflow creation and the refinement provenance by the Pegasus mapping system for execution over grid computing environments. We show how this information is used in answering the queries of the First Provenance Challenge.