The impact of genetic and environmental factors on human brain structure is of great importance for understanding normative cognitive and brain aging as well as neuropsychiatric disorders. However, ...most studies of genetic and environmental influences on human brain structure have either focused on global measures or have had samples that were too small for reliable estimates. Using the classical twin design, we assessed genetic, shared environmental, and individual-specific environmental influences on individual differences in the size of 96 brain regions of interest (ROIs). Participants were 474 middle-aged male twins (202 pairs; 70 unpaired) in the Vietnam Era Twin Study of Aging (VETSA). They were 51–59 years old, and were similar to U.S. men in their age range in terms of sociodemographic and health characteristics. We measured thickness of cortical ROIs and volume of other ROIs. On average, genetic influences accounted for approximately 70% of the variance in the volume of global, subcortical, and ventricular ROIs and approximately 45% of the variance in the thickness of cortical ROIs. There was greater variability in the heritability of cortical ROIs (0.00–0.75) as compared with subcortical and ventricular ROIs (0.48–0.85). The results did not indicate lateralized heritability differences or greater genetic influences on the size of regions underlying higher cognitive functions. The findings provide key information for imaging genetic studies and other studies of brain phenotypes and endophenotypes. Longitudinal analysis will be needed to determine whether the degree of genetic and environmental influences changes for different ROIs from midlife to later life.
Cortical surface area measures appear to be functionally relevant and distinct in etiology, development, and behavioral correlates compared with other size characteristics, such as cortical ...thickness. Little is known about genetic and environmental influences on individual differences in regional surface area in humans. Using a large sample of adult twins, we determined relative contributions of genes and environment on variations in regional cortical surface area as measured by magnetic resonance imaging before and after adjustment for genetic and environmental influences shared with total cortical surface area. We found high heritability for total surface area and, before adjustment, moderate heritability for regional surface areas. Compared with other lobes, heritability was higher for frontal lobe and lower for medial temporal lobe. After adjustment for total surface area, regionally specific genetic influences were substantially reduced, although still significant in most regions. Unlike other lobes, left frontal heritability remained high after adjustment. Thus, global and regionally specific genetic factors both influence cortical surface areas. These findings are broadly consistent with results from animal studies regarding the evolution and development of cortical patterning and may guide future research into specific environmental and genetic determinants of variation among humans in the surface area of particular regions.
Background Although global brain structure is highly heritable, there is still variability in the magnitude of genetic influences on the size of specific regions. Yet, little is known about the ...patterning of those genetic influences, i.e., whether the same genes influence structure throughout the brain or whether there are regionally specific sets of genes. Methods We mapped the heritability of cortical thickness throughout the brain using three-dimensional structural magnetic resonance imaging in 404 middle-aged male twins. To assess the amount of genetic overlap between regions, we then mapped genetic correlations between three selected seed points and all other points comprising the continuous cortical surface. Results There was considerable regional variability in the magnitude of genetic influences on cortical thickness. The primary visual (V1) seed point had strong genetic correlations with posterior sensory and motor areas. The anterior temporal seed point had strong genetic correlations with anterior frontal regions but not with V1. The middle frontal seed point had strong genetic correlations with inferior parietal regions. Conclusions These results provide strong evidence of regionally specific patterns rather than a single, global genetic factor. The patterns are largely consistent with a division between primary and association cortex, as well as broadly defined patterns of brain gene expression, neuroanatomical connectivity, and brain maturation trajectories, but no single explanation appears to be sufficient. The patterns do not conform to traditionally defined brain structure boundaries. This approach can serve as a step toward identifying novel phenotypes for genetic association studies of psychiatric disorders and normal and pathological cognitive aging.
Attentional set-shifting ability, commonly assessed with the Trail Making Test (TMT), decreases with increasing age in adults. Since set-shifting performance relies on activity in widespread brain ...regions, deterioration of the white matter tracts that connect these regions may underlie the age-related decrease in performance. We used an automated fiber tracking method to investigate the relationship between white matter integrity in several cortical association tracts and TMT performance in a sample of 24 healthy adults, 21–80 years. Diffusion tensor images were used to compute average fractional anisotropy (FA) for five cortical association tracts, the corpus callosum (CC), and the corticospinal tract (CST), which served as a control. Results showed that advancing age was associated with declines in set-shifting performance and with decreased FA in the CC and in association tracts that connect frontal cortex to more posterior brain regions, including the inferior fronto-occipital fasciculus (IFOF), uncinate fasciculus (UF), and superior longitudinal fasciculus (SLF). Declines in average FA in these tracts, and in average FA of the right inferior longitudinal fasciculus (ILF), were associated with increased time to completion on the set-shifting subtask of the TMT but not with the simple sequencing subtask. FA values in these tracts were strong mediators of the effect of age on set-shifting performance. Automated tractography methods can enhance our understanding of the fiber systems involved in performance of specific cognitive tasks and of the functional consequences of age-related changes in those systems.
Climate change is an indisputable threat to human health, especially for societies already confronted with rising social inequality, political and economic uncertainty, and a cascade of concurrent ...environmental challenges. Archaeological data about past climate and environment provide an important source of evidence about the potential challenges humans face and the long-term outcomes of alternative short-term adaptive strategies. Evidence from well-dated archaeological human skeletons and mummified remains speaks directly to patterns of human health over time through changing circumstances. Here, we describe variation in human epidemiological patterns in the context of past rapid climate change (RCC) events and other periods of past environmental change. Case studies confirm that human communities responded to environmental changes in diverse ways depending on historical, sociocultural, and biological contingencies. Certain factors, such as social inequality and disproportionate access to resources in large, complex societies may influence the probability of major sociopolitical disruptions and reorganizations-commonly known as "collapse." This survey of Holocene human-environmental relations demonstrates how flexibility, variation, and maintenance of Indigenous knowledge can be mitigating factors in the face of environmental challenges. Although contemporary climate change is more rapid and of greater magnitude than the RCC events and other environmental changes we discuss here, these lessons from the past provide clarity about potential priorities for equitable, sustainable development and the constraints of modernity we must address.
DNA methylation may play an important role in schizophrenia (SZ), either directly as a mechanism of pathogenesis or as a biomarker of risk.
To scan genome-wide DNA methylation data to identify ...differentially methylated CpGs between SZ cases and controls.
Epigenome-wide association study begun in 2008 using DNA methylation levels of 456 513 CpG loci measured on the Infinium HumanMethylation450 array (Illumina) in a consortium of case-control studies for initial discovery and in an independent replication set. Primary analyses used general linear regression, adjusting for age, sex, race/ethnicity, smoking, batch, and cell type heterogeneity. The discovery set contained 689 SZ cases and 645 controls (n = 1334), from 3 multisite consortia: the Consortium on the Genetics of Endophenotypes in Schizophrenia, the Project among African-Americans To Explore Risks for Schizophrenia, and the Multiplex Multigenerational Family Study of Schizophrenia. The replication set contained 247 SZ cases and 250 controls (n = 497) from the Genomic Psychiatry Cohort.
Identification of differentially methylated positions across the genome in SZ cases compared with controls.
Of the 689 case participants in the discovery set, 477 (69%) were men and 258 (37%) were non-African American; of the 645 controls, 273 (42%) were men and 419 (65%) were non-African American. In our replication set, cases/controls were 76% male and 100% non-African American. We identified SZ-associated methylation differences at 923 CpGs in the discovery set (false discovery rate, <0.2). Of these, 625 showed changes in the same direction including 172 with P < .05 in the replication set. Some replicated differentially methylated positions are located in a top-ranked SZ region from genome-wide association study analyses.
This analysis identified 172 replicated new associations with SZ after careful correction for cell type heterogeneity and other potential confounders. The overlap with previous genome-wide association study data can provide potential insights into the functional relevance of genetic signals for SZ.
Abstract
The mitigation of rapid mass movements involves a subtle interplay between field surveys, numerical modelling, and experience. Hazard engineers rely on a combination of best practices and, ...if available, historical facts as a vital prerequisite in establishing reproducible and accurate hazard zoning. Full-scale field tests have been performed to reinforce the physical understanding of debris flows and snow avalanches. Rockfall dynamics are - especially the quantification of energy dissipation during the complex rock-ground interaction - largely unknown. The awareness of rock shape dependence is growing, but presently, there exists little experimental basis on how rockfall hazard scales with rock mass, size, and shape. Here, we present a unique data set of induced single-block rockfall events comprising data from equant and wheel-shaped blocks with masses up to 2670 kg, quantifying the influence of rock shape and mass on lateral spreading and longitudinal runout and hence challenging common practices in rockfall hazard assessment.
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