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

Desempenho, características de carcaça, qualidade da carne e condição sanitária de suínos criados nas fases de crescimento e terminação nos sistemas confinado convencional e de cama sobreposta Performance, carcass characteristics, meat quality and health condition of growing and finishing pigs raised in conventional and deep litter housing systems

O objetivo deste trabalho foi avaliar o efeito do sistema de alojamento sobre o desempenho zootécnico, as características da carcaça, a qualidade da carne e a condição sanitária de suínos criados em seis diferentes sistemas. Foram usados 803 suínos mestiços MS58 x (Landrace x Large White) em sete lotes seqüenciais no tempo, avaliando as fases de creche e de crescimento-terminação. Na creche, foram avaliados três tipos de alojamento: confinado convencional (CO); cama sobreposta-(CS); e sistema intensivo de suínos criados ao ar livre (SISCAL). No crescimento-terminação, foram avaliados apenas dois tipos de alojamento (CO e CS), sendo o último subdividido em três substratos (palha de trigo-PT, casca de arroz-CA e serragem-SE). Para a análise estatística foi considerado no modelo os efeitos de lote, o tratamento (combinação de tipos de alojamento na creche e no crescimento-terminação), idade dos suínos (84, 105, 126, 147 e 160 dias) e a interação tratamento x idade. Suínos alojados no sistema CO apresentaram maior (P<0,05) ganho de peso diário (824 vs. 779g), maior peso de carcaça quente (75 vs. 69kg) e maior espessura de toucinho (18, vs. 17mm) do que os criados sobre cama todavia estes suínos apresentaram peso do conteúdo estomacal significativamente (P<0,05) maior (360 vs. 204g) e menor grau de lesão do estômago do que aqueles alojados em tratamento convencional, embora com maior prevalência de espirro. O sistema de alojamento não afetou os aspectos sanitários avaliados, contudo, suínos alojados em cama sobreposta no crescimento-terminação apresentaram desempenho e características de carcaça inferiores àqueles do sistema convencional, independentemente do sistema de alojamento utilizado na creche.<br>The objective of this study was to evaluate the effect of housing system on live performance, carcass characteristics, meat quality, and the sanitary condition of pigs raised in six different systems. A total of 803 MS58 x (Landrace x Large White) hybrid type pigs was used in seven subsequent lots, during the nursery and growing-finishing phases. At the nursery period, the systems evaluated were: conventional (CO), deep litter (CS), and intensive free range (SISCAL), while during the growing-finishing phase only the CO and CS systems were evaluated, being the CS system subdivided into three substrates (wheat straw, rice hulls and wood shaving). The factors considered on the statistical analysis were lot, treatment (combination of housing type used during nursery and growing-finishing phases), age (84, 105, 126, 147 e 160 days), and the interaction treatment x age. A significant effect of housing type was observed on weight gain, carcass characteristics, and weight of heart, liver, full stomach and stomach content. Animals housed on conventional treatment had higher (P<0.05) weight gain (824 vs. 779g), higher hot carcass weight (75 vs. 69kg) and higher fat thickness (18 vs. 17mm) than the ones raised on deep litter, however, these, on the other hand, presented larger (P<0.05) gut content (360 vs. 204g) and less degree of gut lesion than those of the conventional treatment, eventhough with higher sneeze prevalence. The housing system did not influence the health, however pigs housed on deep litter system during the growing-finishing phase presented lower performance and carcass values than the ones housed in the conventional housing system despite the housing system used during the nursery phase