To examine the genetic and environmental influences on variances in weight, height, and BMI, from birth through 19 years of age, in boys and girls from three continents.
Cross-sectional twin study. ...Data obtained from a total of 23 twin birth-cohorts from four countries: Canada, Sweden, Denmark, and Australia. Participants were Monozygotic (MZ) and dizygotic (DZ) (same- and opposite-sex) twin pairs with data available for both height and weight at a given age, from birth through 19 years of age. Approximately 24,036 children were included in the analyses.
Heritability for body weight, height, and BMI was low at birth (between 6.4 and 8.7% for boys, and between 4.8 and 7.9% for girls) but increased over time, accounting for close to half or more of the variance in body weight and BMI after 5 months of age in both sexes. Common environmental influences on all body measures were high at birth (between 74.1-85.9% in all measures for boys, and between 74.2 and 87.3% in all measures for girls) and markedly reduced over time. For body height, the effect of the common environment remained significant for a longer period during early childhood (up through 12 years of age). Sex-limitation of genetic and shared environmental effects was observed.
Genetics appear to play an increasingly important role in explaining the variation in weight, height, and BMI from early childhood to late adolescence, particularly in boys. Common environmental factors exert their strongest and most independent influence specifically in pre-adolescent years and more significantly in girls. These findings emphasize the need to target family and social environmental interventions in early childhood years, especially for females. As gene-environment correlation and interaction is likely, it is also necessary to identify the genetic variants that may predispose individuals to obesity.
Abstract
Quantifying the genetic architecture of the cerebral cortex is necessary for understanding disease and changes to the brain across the lifespan. Prior work shows that both surface area (SA) ...and cortical thickness (CT) are heritable. However, we do not yet understand the extent to which region-specific genetic factors (i.e., independent of global effects) play a dominant role in the regional patterning or inter-regional associations across the cortex. Using a population sample of young adult twins (N = 923), we show that the heritability of SA and CT varies widely across regions, generally independent of measurement error. When global effects are controlled for, we detected a complex pattern of genetically mediated clusters of inter-regional associations, which varied between hemispheres. There were generally weak associations between the SA of different regions, except within the occipital lobe, whereas CT was positively correlated within lobar divisions and negatively correlated across lobes, mostly due to genetic covariation. These findings were replicated in an independent sample of twins and siblings (N = 698) from the Human Connectome Project. The different genetic contributions to SA and CT across regions reveal the value of quantifying sources of covariation to appreciate the genetic complexity of cortical structures.
Abstract
Objective
There are no large, longitudinal studies of thyroid function across adolescence. The aims of this study were to examine longitudinal trends in thyrotropin (TSH), free ...triiodothyronine (fT3) and free thyroxine (fT4) and determine age-specific reference ranges.
Methods
Thyroid function was assessed in 3415 participants in the Brisbane Longitudinal Twin Study at ages 12, 14, and 16, using the Abbott ARCHITECT immunoassay. Longitudinal analyses were adjusted for body mass index and puberty.
Results
In girls, mean fT4 (± SE) increased between age 12 and 14 (by 0.30 ± 0.08 pmol/L; P < 0.001), while remaining unchanged in boys; from age 14 to 16, fT4 increased in both girls (by 0.42 ± 0.07 pmol/L; P < 0.001) and boys (0.64 ± 0.07 pmol/L, P < 0.001). There was a slight increase in fT3 from age 12 to 14 years in girls (by 0.07 ± 0.03 pmol/L; P = 0.042), with a more marked increase in boys (0.29 ± 0.03 pmol/L; P < 0.001), followed by a decrease from age 14 to 16 in both sexes (girls, by 0.53 ± 0.02 pmol/L; P < 0.001; boys, by 0.62 ± 0.03 pmol/L; P < 0.001). From age 12 to 14, TSH showed no significant change in girls or boys, then levels increased from age 14 to 16 in both sexes (in girls, by 4.9%, 95% CI: 2.4%-10.3%, P = 0.020; in boys, by 7.2%, 95% CI: 3.0%-11.6%, P = 0.001). Reference ranges differed substantially from adults, particularly for fT4 and fT3.
Conclusions
Thyroid function tests in adolescents display complex, sexually dimorphic patterns. Implementation of adolescence-specific reference ranges may be appropriate.
An effective blood-stage vaccine against Plasmodium falciparum remains a research priority, but the number of antigens that have been translated into multicomponent vaccines for testing in clinical ...trials remains limited. Investigating the large number of potential targets found in the parasite proteome has been constrained by an inability to produce natively folded recombinant antigens for immunological studies. We overcame these constraints by generating a large library of biochemically active merozoite surface and secreted full-length ectodomain proteins. We then systematically examined the antibody reactivity against these proteins in a cohort of Kenyan children (n = 286) who were sampled at the start of a malaria transmission season and prospectively monitored for clinical episodes of malaria over the ensuing 6 months. We found that antibodies to previously untested or little-studied proteins had superior or equivalent potential protective efficacy to the handful of current leading malaria vaccine candidates. Moreover, cumulative responses to combinations comprising 5 of the 10 top-ranked antigens, including PF3D7_1136200, MSP2, RhopH3, P41, MSP11, MSP3, PF3D7_0606800, AMA1, Pf113, and MSRP1, were associated with 100% protection against clinical episodes of malaria. These data suggest not only that there are many more potential antigen candidates for the malaria vaccine development pipeline but also that effective vaccination may be achieved by combining a selection of these antigens.
The hippocampus is a brain region critical for learning and memory, and is also implicated in several neuropsychiatric disorders that show sex differences in prevalence, symptom expression, and mean ...age of onset. On average, males have larger hippocampal volumes than females, but findings are inconclusive after adjusting for overall brain size. Although the hippocampus is a heterogenous structure, few studies have focused on sex differences in the hippocampal subfields – with little consensus on whether there are regionally specific sex differences in the hippocampus after adjusting for brain size, or whether it is important to adjust for total hippocampal volume (HPV). Here, using two young adult cohorts from the Queensland Twin IMaging study (QTIM; N = 727) and the Human Connectome Project (HCP; N = 960), we examined differences between males and females in the volumes of 12 hippocampal subfields, extracted using FreeSurfer 6.0. After adjusting the subfield volumes for either HPV or brain size (brain segmentation volume (BSV)) using four controlling methods (allometric, covariate, residual and matching), we estimated the percentage difference of the sex effect (males versus females) and Cohen’s d using hierarchical general linear models. Males had larger volumes compared to females in the parasubiculum (up to 6.04%; Cohen’s d = 0.46) and fimbria (up to 8.75%; d = 0.54) after adjusting for HPV. These sex differences were robust across the two cohorts and multiple controlling methods, though within cohort effect sizes were larger for the matched approach, due to the smaller sub-sample. Additional sex effects were identified in the HCP cohort and combined (QTIM and HCP) sample (hippocampal fissure (up to 6.79%), presubiculum (up to 3.08%), and hippocampal tail (up to −0.23%)). In contrast, no sex differences were detected for the volume of the cornu ammonis (CA)2/3, CA4, Hippocampus-Amygdala Transition Area (HATA), or the granule cell layer of the dentate gyrus (GCDG). These findings show that, independent of differences in HPV, there are regionally specific sex differences in the hippocampus, which may be most prominent in the fimbria and parasubiculum. Further, given sex differences were less consistent across cohorts after controlling for BSV, adjusting for HPV rather than BSV may benefit future studies. This work may help in disentangling sex effects, and provide a better understanding of the implications of sex differences for behaviour and neuropsychiatric disorders.
•Region-specific sex differences were found after adjusting for hippocampal volume.•Males have larger parasubiculum, fimbria, hippocampal fissure, and presubiculum.•Females show larger volumes for the hippocampal tail.•No sex differences were found in the CA2/3, CA4, HATA, or GCDG subfields.
Resting state fMRI (R-fMRI) is a powerful in-vivo tool for examining the functional architecture of the human brain. Recent studies have demonstrated the ability to characterize transitions between ...functionally distinct cortical areas through the mapping of gradients in intrinsic functional connectivity (iFC) profiles. To date, this novel approach has primarily been applied to iFC profiles averaged across groups of individuals, or in one case, a single individual scanned multiple times. Here, we used a publically available R-fMRI dataset, in which 30 healthy participants were scanned 10 times (10 min per session), to investigate differences in full-brain transition profiles (i.e., gradient maps, edge maps) across individuals, and their reliability. 10-min R-fMRI scans were sufficient to achieve high accuracies in efforts to "fingerprint" individuals based upon full-brain transition profiles. Regarding test-retest reliability, the image-wise intraclass correlation coefficient (ICC) was moderate, and vertex-level ICC varied depending on region; larger durations of data yielded higher reliability scores universally. Initial application of gradient-based methodologies to a recently published dataset obtained from twins suggested inter-individual variation in areal profiles might have genetic and familial origins. Overall, these results illustrate the utility of gradient-based iFC approaches for studying inter-individual variation in brain function.
Adolescence is a risk period for the development of mental illness, as well as a time for pronounced change in sleep behaviour. While prior studies, including several meta-analyses show a ...relationship between sleep and depressive symptoms, there were many inconsistences found in the literature.
To investigate the relationship between subjective sleep and depressive symptoms.
Following PRISMA guidelines, we conducted a literature search that yielded forty-nine recent studies (2014–2020) with adolescent samples aged 9 to 25-year-olds, and more than double the sample size of previous meta-analyses (N = 318,256).
In a series of meta-analyses, we show that while several common categories of subjective sleep are associated with depressive symptoms in adolescents, the strength of this relationship varies. Measures of sleep perception: poor sleep quality (r = 0.41), insomnia (r = 0.37), sleep disturbances (r = 0.36), wake after sleep onset (r = 0.31), and daytime sleepiness (r = 0.30) correlated more strongly with depressive symptoms, than measures of sleep behaviour: sleep latency (r = 0.22), and sleep duration (r = −0.19).
These findings suggest that in studies of depressive symptoms it may be important to assess an adolescent's perception about their sleep, in addition to their sleep/wake behaviours.
•Largest analysis of the relationship between sleep and depression in adolescence.•All sleep measures were associated with depressive symptoms, but not equally.•Stronger associations for sleep perception than sleep/wake behaviour.•When considering adolescent depression, it is vital to also assess sleep quality.
There is increasing interest in the potential contribution of the gut microbiome to autism spectrum disorder (ASD). However, previous studies have been underpowered and have not been designed to ...address potential confounding factors in a comprehensive way. We performed a large autism stool metagenomics study (n = 247) based on participants from the Australian Autism Biobank and the Queensland Twin Adolescent Brain project. We found negligible direct associations between ASD diagnosis and the gut microbiome. Instead, our data support a model whereby ASD-related restricted interests are associated with less-diverse diet, and in turn reduced microbial taxonomic diversity and looser stool consistency. In contrast to ASD diagnosis, our dataset was well powered to detect microbiome associations with traits such as age, dietary intake, and stool consistency. Overall, microbiome differences in ASD may reflect dietary preferences that relate to diagnostic features, and we caution against claims that the microbiome has a driving role in ASD.
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•Limited autism-microbiome associations from stool metagenomics of n = 247 children•Romboutsia timonensis was the only taxa associated with autism diagnosis•Autistic traits such as restricted interests are associated with less-diverse diet•Less-diverse diet, in turn, is associated with lower microbiome alpha-diversity
Large autism stool metagenomics study finds limited direct autism associations, in contrast to strong relationships with dietary traits, stool consistency, and age, suggestive of a model whereby genetic and phenotypic measures of the autism spectrum promote a less-diverse diet that reduces microbiome diversity.
One of the grand challenges faced by neuroscience is to delineate the determinants of interindividual variation in the comprehensive structural and functional connection matrices that comprise the ...human connectome. At present, this endeavor appears most tractable at the macroanatomic scale, where intrinsic brain activity exhibits robust patterns of synchrony that recapitulate core functional circuits at the individual level. Here, we use a classical twin study design to examine the heritability of intrinsic functional network properties in 101 twin pairs, including network activity (i.e., variance of a network's specific temporal fluctuations) and internetwork coherence (i.e., correlation between networks' specific temporal fluctuations). Five of 7 networks exhibited significantly heritable (23.3-65.2%) network activity, 6 of the 21 internetwork coherences were significantly heritable (25.6-42.0%), and 11 of the 21 internetwork coherences were significantly influenced by common environmental factors (18.0-47.1%). These results suggest that the source of interindividual variation in functional connectome has a modular architecture: individual modules represented by intrinsic connectivity networks are genetic controlled, while environmental factors influence the interplays between the modules. This work further provides network-specific hypotheses for discovery of the specific genetic and environmental factors influencing functional specialization and integration of the human brain.
Traits that are attractive to the opposite sex are often positively correlated when scaled such that scores increase with attractiveness, and this correlation typically has a genetic component. Such ...traits can be genetically correlated due to genes that affect both traits ("pleiotropy") and/or because assortative mating causes statistical correlations to develop between selected alleles across the traits ("gametic phase disequilibrium"). In this study, we modeled the covariation between monozygotic and dizygotic twins, their siblings, and their parents (total N = 7,905) to elucidate the nature of the correlation between two potentially sexually selected traits in humans: height and IQ. Unlike previous designs used to investigate the nature of the height-IQ correlation, the present design accounts for the effects of assortative mating and provides much less biased estimates of additive genetic, non-additive genetic, and shared environmental influences. Both traits were highly heritable, although there was greater evidence for non-additive genetic effects in males. After accounting for assortative mating, the correlation between height and IQ was found to be almost entirely genetic in nature. Model fits indicate that both pleiotropy and assortative mating contribute significantly and about equally to this genetic correlation.
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