The genetic architecture of the human cerebral cortex

INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 10 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. CONCLUSION This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function

Interactive effects of light, leaf temperature, CO 2 and O 2 on photosynthesis in soybean

A biochemical model of C 3 photosynthesis has been developed by G.D. Farquhar et al. (1980, Planta 149, 78–90) based on Michaelis-Menten kinetics of ribulose-1,5-bisphosphate (RuBP) carboxylase-oxygenase, with a potential RuBP limitation imposed via the Calvin cycle and rates of electron transport. The model presented here is slightly modified so that parameters may be estimated from whole-leaf gas-exchange measurements. Carbon-dioxide response curves of net photosynthesis obtained using soybean plants ( Glycine max (L.) Merr.) at four partial pressures of oxygen and five leaf temperatures are presented, and a method for estimating the kinetic parameters of RuBP carboxylase-oxygenase, as manifested in vivo, is discussed. The kinetic parameters so obtained compare well with kinetic parameters obtained in vitro, and the model fits to the measured data give r 2 values ranging from 0.87 to 0.98. In addition, equations developed by J.D. Tenhunen et al. (1976, Oecologia 26, 89–100, 101–109) to describe the light and temperature responses of measured CO 2 -saturated photosynthetic rates are applied to data collected on soybean. Combining these equations with those describing the kinetics of RuBP carboxylase-oxygenase allows one to model successfully the interactive effects of incident irradiance, leaf temperature, CO 2 and O 2 on whole-leaf photosynthesis. This analytical model may become a useful tool for plant ecologists interested in comparing photosynthetic responses of different C 3 plants or of a single species grown in contrasting environments.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47469/1/425_2004_Article_BF00395048.pd

Data Report: Microfabric Analysis of Postglacial Sediments from Palmer Deep, Western Antarctic Peninsula

The Antarctic Peninsula region is ideally suited to monitor how global change affects Antarctica because it is one of the most sensitive regions of the continent to rapid climate change. This has been clearly demonstrated by the recent break up of the Larsen A Ice Shelf. Drilling at Ocean Drilling Program Site 1098, Palmer Deep, western Antarctic Peninsula, recovered almost 50 m of sediments that record the paleoceanographic and paleoclimatic history of the region from the last glacial maximum through the rapid climate oscillations of deglaciation into the Holocene. This sedimentary section will provide a wealth of high-resolution paleoenvironmental data from Antarctica that will be useful for climate modelers and paleoceanographers alike. This data report presents the preliminary results of a high-resolution, microscale sediment fabric study of the postglacial sediments from Palmer Deep Site 1098. These sediments have previously been described as being annually laminated; however, this investigation shows that although the interpretation of this sequence as seasonal sediments is most likely correct, there are a number of features that indicate there is strong interannual variability affecting the laminations

Comparison of contemporary and fossil diatom assemblages from the western Antarctic Peninsula shelf

During the past ten years, the Antarctic Peninsula has been identified as the most rapidly warming region of the Southern Hemisphere and it is important to place this warming in the context of the natural climate and oceanographic variability of the recent geological past. Many biological proxies, such as marine diatom assemblages, have been used to determine Southern Ocean palaeoceanographic conditions during the Late Quaternary, however, few investigations have attempted to link observations of modern floras with the fossil record. In this study we examine a suite of modern austral spring (December 2003) and summer (February 2002) surface water samples from along the western Antarctic Peninsula (WAP) continental shelf and compare these to core-top, surface sediment samples. Using detrended correspondence analysis (DCA) and principal component analysis (PCA) of diatom abundance data we investigate the relationship of contemporary diatom floras with the fossil record. This multivariate analysis reveals that our modern assemblages can be divided into three groups: summer southern WAP sites, summer northern WAP sites, and spring WAP sites. Sea surface temperature (SST) is an important environmental variable for explaining seasonal differences in diatom assemblages between spring and summer, but sea surface salinity (SSS) is more important for understanding temporally-equivalent regional variations in assemblage. Our summer diatom samples are more reminiscent of early season assemblages, reflecting the unusually late sea ice retreat from the region that year. When the modern assemblages are compared to the fossil record, it is clear that most of the important diatoms from the summer assemblage are not preserved into the sediments, and that the fossil record more closely reflects spring assemblages. This observation is important for any future attempts to quantitatively reconstruct palaeoceanographic conditions along the WAP during the Late Quaternary and highlights the need for many more such studies in order to address longer timescales, such as interannual variability, in the context of the fossil record. (c) 2008 Elsevier B.V. All rights reserved