Biology subjects

Clasen, L.

Publications and source records attributed to Clasen, L..

4 recordsLinked to original sources

bioRxiv2026

Sex Differences in Human Subcortical Anatomy are Robust and Replicable in Adulthood, Already Evident Prepubertally, and Aligned with Sex Chromosomal and Gonadal Influences

The existence and mechanistic bases of sex effects on human subcortical anatomy remain unclear. To address these gaps, we combined structural neuroimaging of sex differences in subcortical volume and shape across three independent cohorts (combined N=2,886) with neuroimaging maps of sex chromosomal and endocrine effects from three clinical cohorts (combined N=313, including sex chromosome aneuploidies and isolated gonadotropin-releasing hormone deficiency). We found that human subcortical anatomy shows focal sex differences of moderate-strong effect size during young adulthood (male-biased surface area overlying lateral/ventral putamen and pallidum, nucleus accumbens, ventral posterior complex of thalamus, anterior hippocampus, and medial and central nuclei of amygdala; female-biased surface area overlying caudate head, posterior/dorsal pallidum, mediodorsal, lateral dorsal, lateral geniculate, and medial geniculate nuclei of thalamus, posterior hippocampus, and basolateral and lateral nuclei of amygdala). These regional sex differences show strong within-sample reproducibility at modest sample sizes (N[≥]200) and are replicable in a fully independent mid-adulthood cohort. Adult subcortical sex differences are already evident in nascent form by pre/early puberty (age 9 years), and the same holds for cortical sex differences. Comparison with neuroimaging data from rare disorder cohorts reveals a statistically significant spatial and directional congruence of subcortical sex differences with the anatomical effects of X-chromosome dosage in the striatum and effects of testicular hormones in the amygdala. Our findings provide a reference map for the fine-grained spatial patterning of sex differences in adult subcortical shape, demonstrating its replicability, establishment before pubertal progression, and spatial concordance with potentially causal sex chromosomal and gonadal effects.

neuroscience↗

bioRxiv2025

Fractionation of sex differences in human cortical anatomy

Humans show reproducible sex differences in regional cortical volume (CV), but it remains unclear how these arise from underlying sex-biases in the two biologically dissociable determinants of CV: surface area (SA) and cortical thickness (CT). Moreover, limited access to experimental methods in humans has hindered direct studies of the causal drivers of regional sex differences in the human cortex, although rodent models have argued for both chromosomal and gonadal contributions to sex-biased mammalian cortical development. Here, we first use structural neuroimaging data in two independent human cohorts (combined N=1,754; 967 females) to quantify and spatially resolve the differential contributions of SA and CT to observed sex differences in CV. These dissociable facets of sex-biased cortical organization are highly reproducible and align with distinct functional networks and histo-molecular signatures. We then leverage complementary neuroimaging data in clinical case-control cohorts (combined N=313) featuring variations in X and Y chromosome dosage (sex chromosome aneuploidies) and testicular hormone production (isolated GnRH deficiency) to establish that regions of sex-biased CV, SA and CT in humans are enriched for congruent anatomical effects of X-chromosome dosage (e.g., primary sensory and insular cortices) and gonadal hormones (e.g. dorsomedial frontal and temporo-parietal-occipital regions). Taken together, these findings substantially advance both the breadth and granularity of our understanding regarding sex-biased cortical organization in humans - disambiguating sex effects on regional CV, SA and CT and nominating their potential genetic and endocrine causes.

neuroscience↗

bioRxiv2017

Sex Chromosome Dosage Effects On Gene Expression In Humans

A fundamental question in the biology of sex-differences has eluded direct study in humans: how does sex chromosome dosage (SCD) shape genome function? To address this, we developed a systematic map of SCD effects on gene function by analyzing genome-wide expression data in humans with diverse sex chromosome aneuploidies (XO, XXX, XXY, XYY, XXYY). For sex chromosomes, we demonstrate a pattern of obligate dosage sensitivity amongst evolutionarily preserved X-Y homologs, and update prevailing theoretical models for SCD compensation by detecting X-linked genes whose expression increases with decreasing X- and/or Y-chromosome dosage. We further show that SCD-sensitive sex chromosome genes regulate specific co-expression networks of SCD-sensitive autosomal genes with critical cellular functions and a demonstrable potential to mediate previously documented SCD effects on disease. Our findings detail wide-ranging effects of SCD on genome function with implications for human phenotypic variation.\n\nSIGNIFICANCE STATEMENTSex chromosome dosage (SCD) effects on human gene expression are central to the biology of sex differences and sex chromosome aneuploidy syndromes, but challenging to study given the co-segregation of SCD and gonadal status. We address this obstacle by systematically modelling SCD effects on genome wide expression data from a large and rare cohort of individuals with diverse SCDs (XO, XX, XXX, XXXX, XY, XXY, XYY, XXYY, XXXXY). Our findings update current models of sex chromosome biology by (i) pinpointing a core set of X- and Y-linked genes with \"obligate\" SCD sensitivity, (ii) discovering several non-canonical modes of X-chromosome dosage compensation, and (iii) dissecting complex regulatory effects of X-chromosome dosage on large autosomal gene networks with key roles in cellular functioning.

genomics↗

bioRxiv2017

Morphometric Similarity Networks Detect Microscale Cortical Organisation And Predict Inter-Individual Cognitive Variation

Macroscopic cortical networks are important for cognitive function, but it remains challenging to construct anatomically plausible individual structural connectomes from human neuroimaging. We introduce a new technique for cortical network mapping, based on inter-regional similarity of multiple morphometric parameters measured using multimodal MRI. In three cohorts (two human, one macaque), we find that the resulting morphometric similarity networks (MSNs) have a complex topological organisation comprising modules and high-degree hubs. Human MSN modules recapitulate known cortical cytoarchitectonic divisions, and greater inter-regional morphometric similarity was associated with stronger inter-regional co-expression of genes enriched for neuronal terms. Comparing macaque MSNs to tract-tracing data confirmed that morphometric similarity was related to axonal connectivity. Finally, variation in the degree of human MSN nodes accounted for about 40% of between-subject variability in IQ. Morphometric similarity mapping provides a novel, robust and biologically plausible approach to understanding how human cortical networks underpin individual differences in psychological functions.

neuroscience↗