Genetic associations between intelligence and cortical thickness emerge at the start of puberty

Cognitive abilities are related to (changes in) brain structure during adolescence and adulthood. Previous studies suggest that associations between cortical thickness and intelligence may be different at different ages. As both intelligence and cortical thickness are heritable traits, the question arises whether the association between cortical thickness development and intelligence is due to genes influencing both traits. We study this association in a longitudinal sample of young twins. Intelligence was assessed by standard IQ tests at age 9 in 224 twins, 190 of whom also underwent structural magnetic resonance imaging (MRI). Three years later at age 12, 177/125 twins returned for a follow‐up measurement of intelligence/MRI scanning, respectively. We investigated whether cortical thickness was associated with intelligence and if so, whether this association was driven by genes. At age 9, there were no associations between cortical thickness and intelligence. At age 12, a negative relationship emerged. This association was mainly driven by verbal intelligence, and manifested itself most prominently in the left hemisphere. Cortical thickness and intelligence were explained by the same genes. As a post hoc analysis, we tested whether a specific allele (rs6265; Val66Met in the BDNF gene) contributed to this association. Met carriers showed lower intelligence and a thicker cortex, but only the association between the BDNF genotype and cortical thickness in the left superior parietal gyrus reached significance. In conclusion, it seems that brain areas contributing to (verbal) intellectual performance are specializing under the influence of genes around the onset of puberty. Hum Brain Mapp 35:3760–3773, 2014. © 2013 Wiley Periodicals, Inc .     

HL-A Typing of Kidney Cells and Lymphocytes

Abstract. Fresh human kidney cells were typed for HL-A antigens by means of the micro-immune adherence assay (MIAA). Lymphocytes from the same individuals were typed both by means of the MIAA and the microcytotoxicity test. Difference in typing results between the two types of cells was observed in 10% of the cases. When cultured kidney cells were used for HL-A typing, a greater difference was found, namely 28%. This can be explained by the poor reproducibility of the MIAA if performed on cultured kidney cells.
In 7% of all cases, an HL-A factor was found on kidney cells which could not be demonstrated on the lymphocytes. This may be explained by the fact that the MIAA of fresh kidney cells is more sensitive for detecting HL-A antigens than the MIAA or the microcytotoxicity test of lymphocytes. Lymphocytes not reacting in the MIAA were able to absorb antibodies from the anti-HL-A sera that showed a positive reaction in the MIAA with fresh kidney cells from the same individuals. In one case, absorption of antibodies by lymphocytes could not be demonstrated. Kidney-specific antibodies could not be detected in anti-HL-A sera, nor could differences in typing results between the two types of cells be explained by the presence of blood-group antibodies.     

Genetic control of functional brain network efficiency in children

The human brain is a complex network of interconnected brain regions. In adulthood, the brain's network was recently found to be under genetic influence. However, the extent to which genes influence the functional brain network early in development is not yet known. We report on the heritability of functional brain efficiency during early brain development. Using a twin design, young children underwent resting-state functional magnetic resonance imaging brain scans (N=86 from 21 MZ and 22 DZ twin-pairs, age=12 years). Functional connectivity, defined as the temporal dependency of neuronal activation patterns of anatomically separated brain regions, was explored using graph theory and its heritability was examined using structural equation modeling. Our findings suggest that ‘global efficiency of communication’ among brain regions is under genetic control (h² lambda=42%), irrespectively of the total number of brain connections (connectivity density). In addition, no influence of genes or common environment to local clustering (gamma) was found, suggesting a less pronounced effect of genes on local information segregation. Thus our findings suggest that a set of genes is shaping the underlying architecture of functional brain communication during development.     

Effect of Ascaris Lumbricoides specific IgE on tuberculin skin test responses in children in a high-burden setting: a cross-sectional community-based study

ABSTRACT: BACKGROUND: M.tuberculosis (M.tb) is associated with enhanced T helper cell type 1 (Th1) immune responses while helminth infection is associated with T helper cell type 2 (Th2) immune responses. Our aim was to investigate whether helminth infection could influence the ability to generate an appropriate Th1 immune response that is characterized by a positive tuberculin skin test (TST), in M.tb exposed children. METHODS: We completed a community-based, cross sectional household contact tracing study, using matched enrolment of HIV negative children with and without documented household M.tb exposure. We documented demographics, clinical characteristics, HIV status, M.tb exposure (using a standard contact score) and M.tb infection status (TST > = 10 mm). Ascaris lumbricoides-specific IgE was used as proxy for Ascaris infection/exposure. RESULTS: Of 271 children (median age 4 years (range: 4 months to 15 years)) enrolled, 65 participants (24%) were serum positive for Ascaris IgE. There were 168 (62%) children with a documented household tuberculosis contact and 107 (40%) were (TST) positive overall. A positive TST was associated with increasing age (Odds Ratio (OR) =1.17, p < 0.001), increasing M.tb contact score (OR = 1.17, p < 0.001), previous tuberculosis treatment (OR = 4.8, p = 0.06) and previous isoniazid preventive treatment (OR = 3.16, p = 0.01). A visible bacillus Calmette-Guerin (BCG) scar was associated with reduced odds of being TST positive (OR = 0.42, p = 0.01). Ascaris IgE was not associated with TST status in univariate analysis (OR = 0.9, p = 0.6), but multivariable logistic regression analysis suggested an inverse association between Ascaris IgE status and a positive TST (OR = 0.6, p = 0.08), when adjusted for age, and M.tb contact score. The addition of an age interaction term to the model suggested that the age effect was stronger among Ascaris IgE positive children; the effect of being Ascaris IgE positive significantly reduced the odds of being TST positive amongst younger children while this effect weakened with increasing age. CONCLUSIONS: Our preliminary findings highlight a high prevalence of both Ascaris exposure/infection and M.tb infection in children in an urban setting. Helminth exposure/infection may reduce the immune response following M.tb exposure when controlling for epidemiological and clinical covariates. These findings might be relevant to the interpretation of immunological tests of M.tb infection in children.     

Association between structural brain network efficiency and intelligence increases during adolescence

Adolescence represents an important period during which considerable changes in the brain take place, including increases in integrity of white matter bundles, and increasing efficiency of the structural brain network. A more efficient structural brain network has been associated with higher intelligence. Whether development of structural network efficiency is related to intelligence, and if so to which extent genetic and environmental influences are implicated in their association, is not known. In a longitudinal study, we mapped FA‐weighted efficiency of the structural brain network in 310 twins and their older siblings at an average age of 10, 13, and 18 years. Age‐trajectories of global and local FA‐weighted efficiency were related to intelligence. Contributions of genes and environment were estimated using structural equation modeling. Efficiency of brain networks changed in a non‐linear fashion from childhood to early adulthood, increasing between 10 and 13 years, and leveling off between 13 and 18 years. Adolescents with higher intelligence had higher global and local network efficiency. The dependency of FA‐weighted global efficiency on IQ increased during adolescence (r_ph=0.007 at age 10; 0.23 at age 18). Global efficiency was significantly heritable during adolescence (47% at age 18). The genetic correlation between intelligence and global and local efficiency increased with age; genes explained up to 87% of the observed correlation at age 18. In conclusion, the brain's structural network differentiates depending on IQ during adolescence, and is under increasing influence of genes that are also associated with intelligence as it develops from late childhood to adulthood.     

Genetic influence demonstrated for MEG‐recorded somatosensory evoked responses

We tested for a genetic influence on magnetoencephalogram (MEG)‐recorded somatosensory evoked fields (SEFs) in 20 monozygotic (MZ) and 14 dizygotic (DZ) twin pairs. Previous electroencephalogram (EEG) studies that demonstrated a genetic contribution to evoked responses generally focused on characteristics of representative brain potentials. Here we demonstrate significantly smaller amplitude differences within MZ compared to DZ twin pairs for the complete SEF time series (across left and right hand SEFs: 0.37 vs. 0.60 pT² and 0.28 vs. 0.39 pT² for primary [SI] and secondary [SII] sensory cortex activation) and higher MZ than DZ wave shape correlations (.71 vs. .44 and .52 vs. .35 for SI and SII activation). Our findings indicate a genetic influence on MEG‐recorded evoked brain activity and also confirm our recent conclusion ( van 't Ent, van Soelen, Stam, De Geus, & Boomsma, 2009 ) that higher MZ resemblance for EEG amplitudes is not trivially reflecting greater MZ concordance in intervening biological tissues.     

Genetic influences on thinning of the cerebral cortex during development

During development from childhood to adulthood the human brain undergoes considerable thinning of the cerebral cortex. Whether developmental cortical thinning is influenced by genes and if independent genetic factors influence different parts of the cortex is not known. Magnetic resonance brain imaging was done in twins at age 9 (N = 190) and again at age 12 (N = 125; 113 repeated measures) to assess genetic influences on changes in cortical thinning. We find considerable thinning of the cortex between over this three year interval (on average 0.05 mm; 1.5%), particularly in the frontal poles, and orbitofrontal, paracentral, and occipital cortices. Cortical thinning was highly heritable at age 9 and age 12, and the degree of genetic influence differed for the various areas of the brain. One genetic factor affected left inferior frontal (Broca's area), and left parietal (Wernicke's area) thinning; a second factor influenced left anterior paracentral (sensory-motor) thinning. Two factors influenced cortical thinning in the frontal poles: one of decreasing influence over time, and another independent genetic factor emerging at age 12 in left and right frontal poles. Thus, thinning of the cerebral cortex is heritable in children between the ages 9 and 12. Furthermore, different genetic factors are responsible for variation in cortical thickness at ages 9 and 12, with independent genetic factors acting on cortical thickness across time and between various brain areas during childhood brain development.