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

Age and composition of the Amanay Seamount, Canary Islands

A number of samples have been dredged from the upper parts of Amanay and El Banquete Seamounts, yet volcanic materials have been collected only on Amanay Seamount. Based on textural features and the presence or absence of kaersutite, two main types of olivine pyroxene basaltic rocks have been identified. The rocks are basanites with high enrichment in the most incompatible elements, similar to that displayed by Ocean Island Basalts. Samples from Amanay Seamount formed due to a low degree of melting of an enriched mantle, very similar to that which probably caused the Miocene volcanic activity of Fuerteventura. The age of Amanay volcanic rocks, 15.3 ± 0.4 and 13.1 ± 0.3 Ma, is similar to those of the older volcanic units exposed in the nearby islands (Gran Canaria, Fuerteventura and Lanzarote). This proves the formation of a separate submarine volcanic edifice coeval with the other edifices of the Eastern Canarian Volcanic Ridge. Volcanic activity on the submarine edifice is thought to have ceased at about 13 Ma, simultaneous with the adjacent main volcanic construction

Dolerites of Svalbard, north-west Barents Sea Shelf: age, tectonic setting and significance for geotectonic interpretation of the High-Arctic Large Igneous Province

The dolerites of Svalbard are mineralogically and geochemically homogeneous with geochemical features typical of continental within-plate tholeiites. Their geochemistry is similar to tholeiites belonging to a bimodal suite defined as the High-Arctic Large Igneous Province (HALIP). K–Ar dating of numerous dolerites sampled from many locations across Svalbard define a narrow time span of this magmatism from 125.5±3.6 to 78.3±2.6 Mya. Discrete peaks of intensive activity occurred at 115.3, 100.8, 91.3 and 78.5 Mya corresponding to (1) breakup of the continental crust and formation of an initial rift as a result of mantle plume activity, located in the southern part of the Alpha Ridge; (2) magmatic activity related to spreading along the Alpha Ridge that led to the development of the initial oceanic crust and (3) continuation of spreading along the Alpha Ridge and termination of magmatic activity related to HALIP (last two peaks at 91.3 and 78.5 Mya)