62 research outputs found
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
Conversations in a Crowded Room: An Assessment of the Contribution of Historical Research to Criminology
The relationship between history and social science generally, as well as history and criminology specifically, has long been considered problematic. But, since the likes of Burke (1992) and King (1999) spoke of a ‘dialogue of the deaf’, crime history has rapidly expanded and, more latterly, historical criminology has begun to emerge. This article reappraises the relationship of the subject areas by considering the impact that historical research has had on criminology. Although the impact is found to be somewhat patchy, the article identifies positive signs within the two fields that might point towards a more mutually‐enriching future
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Effect of Whole Cottonseed, Gossypol, and Ruminally Protected Lysine Supplementation on Milk Yield and Composition
To determine whether the gossypol content of the diet affected availability of dietary Lys, 4 cows with ruminal and duodenal cannulas and 16 intact cows in early lactation were assigned to diets containing either glanded cottonseed, glanded cottonseed plus 15 g/d of ruminally protected Lys, glandless cottonseed, or glandless cottonseed plus 15 g/d of ruminally protected Lys. The experimental design was a 4 × 4 Latin square design with 3-wk experimental periods.
Gossypol concentrations in plasma were lower when cows were fed glandless cottonseed. Lysine supplementation increased the flow and percentage of Lys in duodenal digesta and increased the concentration of Lys in plasma. Neither type of cottonseed nor Lys supplementation affected dry matter intake. Yields of milk and fat-corrected milk from cannulated cows were not affected by diet, but yields from intact cows were increased by Lys supplementation. For both cannulated and intact cows, Lys supplementation increased the percentage of milk protein, and milk protein yield was increased by Lys in intact cows. Dietary gossypol did not affect the response to Lys, indicating that dietary gossypol had little or no effect on the availability of Lys for dairy cows
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