<i>APOE</i> ɛ2 vs <i>APOE</i> ɛ4 dosage shows sex-specific links to hippocampus-default network subregion co-variation

Savignac, Chloé; Villeneuve, Sylvia; Badhwar, AmanPreet; Saltoun, Karin; Shafighi, Kimia; Zajner, Chris; Sharma, Vaibhav; Taliun, Sarah A. Gagliano; Farhan, Sali M.K.; Poirier, Judes; Bzdok, Danilo

doi:10.1101/2022.03.15.484482

Cited by 3 publications

(1 citation statement)

References 175 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We performed a rich annotation of the derived intermediate phenotypes by means of a phenomewide association analysis benefitting from a wide variety of almost 1,000 lifestyle factors. For a detailed description of phenotype extraction and analysis, refer to our previously published studies (Saltoun et al, 2022;Savignac et al, 2022). Feature extraction was carried out using two utilities designed to obtain, clean and normalize UKBB phenotype data according to predefined rules.…”

Section: Charting Complex Association Using Phenom-wide Association S...mentioning

confidence: 99%

Rare CNVs and phenome-wide profiling: a tale of brain-structural divergence and phenotypical convergence

Kopál

Kumar

Saltoun

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Copy number variations (CNVs) are rare genomic deletions and duplications that can exert profound effects on brain and behavior. Previous reports of pleiotropy in CNVs imply that they converge on shared mechanisms at some level of pathway cascades, from genes to large-scale neural circuits to the phenome. However, studies to date have primarily examined single CNV loci in small clinical cohorts. It remains unknown how distinct CNVs escalate the risk for the same developmental and psychiatric disorders. Here, we quantitatively dissect the impact on brain organization and behavioral differentiation across eight key CNVs. In 534 clinical CNV carriers from multiple sites, we explored CNV-specific brain morphology patterns. We extensively annotated these CNV-associated patterns with deep phenotyping assays through the UK Biobank resource. Although the eight CNVs cause disparate brain changes, they are tied to similar phenotypic profiles across ∼1000 lifestyle indicators. Our population-level investigation established brain structural divergences and phenotypical convergences of CNVs, with direct relevance to major brain disorders.

show abstract

Section: Charting Complex Association Using Phenom-wide Association S...mentioning

confidence: 99%

Rare CNVs and phenome-wide profiling: a tale of brain-structural divergence and phenotypical convergence

Kopál

Kumar

Saltoun

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

Rare CNVs and phenome-wide profiling highlight brain structural divergence and phenotypical convergence

et al. 2023

Self Cite

View full text Add to dashboard Cite

Copy number variations (CNVs) are rare genomic deletions and duplications that can affect brain and behaviour. Previous reports of CNV pleiotropy imply that they converge on shared mechanisms at some level of pathway cascades, from genes to large-scale neural circuits to the phenome. However, existing studies have primarily examined single CNV loci in small clinical cohorts. It remains unknown, for example, how distinct CNVs escalate vulnerability for the same developmental and psychiatric disorders. Here we quantitatively dissect the associations between brain organization and behavioural differentiation across 8 key CNVs. In 534 CNV carriers, we explored CNV-specific brain morphology patterns. CNVs were characteristic of disparate morphological changes involving multiple large-scale networks. We extensively annotated these CNV-associated patterns with ~1,000 lifestyle indicators through the UK Biobank resource. The resulting phenotypic profiles largely overlap and have body-wide implications, including the cardiovascular, endocrine, skeletal and nervous systems. Our population-level investigation established brain structural divergences and phenotypical convergences of CNVs, with direct relevance to major brain disorders.

show abstract

Longitudinal microstructural changes in 18 amygdala nuclei resonate with cortical circuits and phenomics

Ghanem,

Saltoun,

Suvrathan

et al. 2024

Commun Biol

View full text Add to dashboard Cite

The amygdala nuclei modulate distributed neural circuits that most likely evolved to respond to environmental threats and opportunities. So far, the specific role of unique amygdala nuclei in the context processing of salient environmental cues lacks adequate characterization across neural systems and over time. Here, we present amygdala nuclei morphometry and behavioral findings from longitudinal population data (>1400 subjects, age range 40-69 years, sampled 2-3 years apart): the UK Biobank offers exceptionally rich phenotyping along with brain morphology scans. This allows us to quantify how 18 microanatomical amygdala subregions undergo plastic changes in tandem with coupled neural systems and delineating their associated phenome-wide profiles. In the context of population change, the basal, lateral, accessory basal, and paralaminar nuclei change in lockstep with the prefrontal cortex, a region that subserves planning and decision-making. The central, medial and cortical nuclei are structurally coupled with the insular and anterior-cingulate nodes of the salience network, in addition to the MT/V5, basal ganglia, and putamen, areas proposed to represent internal bodily states and mediate attention to environmental cues. The central nucleus and anterior amygdaloid area are longitudinally tied with the inferior parietal lobule, known for a role in bodily awareness and social attention. These population-level amygdala-brain plasticity regimes in turn are linked with unique collections of phenotypes, ranging from social status and employment to sleep habits and risk taking. The obtained structural plasticity findings motivate hypotheses about the specific functions of distinct amygdala nuclei in humans.

show abstract

APOE ɛ2 vs APOE ɛ4 dosage shows sex-specific links to hippocampus-default network subregion co-variation

Cited by 3 publications

References 175 publications

Rare CNVs and phenome-wide profiling: a tale of brain-structural divergence and phenotypical convergence

Rare CNVs and phenome-wide profiling: a tale of brain-structural divergence and phenotypical convergence

Rare CNVs and phenome-wide profiling highlight brain structural divergence and phenotypical convergence

Longitudinal microstructural changes in 18 amygdala nuclei resonate with cortical circuits and phenomics

Contact Info

Product

Resources

About