Heritability and interindividual variability of regional structure-function coupling.
Ontology highlight
ABSTRACT:
SUBMITTER: Gu Z
PROVIDER: S-EPMC8361191 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:We used an unbiased approach to identify differences in gene expression that may account for the high degree of interindividual variability in inflammatory responses to LPS in the normal human population. We measured LPS-induced cytokine production ex vivo in whole blood from 102 healthy human subjects and identified individuals who consistently showed either very high or very low responses to LPS. Comparison of gene expression profiles between the lpshigh and lpslow individuals revealed 80 genes that were differentially expressed in the presence of LPS and 21 genes that were differentially expressed in the absence of LPS (p < 0.005, ANOVA). Expression of a subset of these genes was confirmed using real-time RT-PCR. These data illustrate a novel approach to the identification of factors that determine interindividual variability in innate immune inflammatory responses. Keywords: comparative response
2005-10-22 | GSE3491 | GEO
Project description:Profiling of DNA methylation and CxxC recruitment in Tc1 mice
2021-10-20 | GSE176176 | GEO
Project description:Understanding the heritable contribution of vascular measures, from parent to offspring, may aid in risk stratification and atherosclerosis prevention efforts. We hypothesized that measures of vascular structure and function would be heritable in this cohort of parents and their adolescent offspring.High-resolution ultrasound scans of the brachial and carotid arteries were obtained in parents (n=558) and their offspring (n=369). Lumen diameter and flow-mediated dilation were measured in the brachial artery. Intima-media thickness, lumen diameter, incremental elastic modulus, diameter distensibility, and cross-sectional distensibility were measured, and carotid cross-sectional compliance was measured in the carotid artery. Carotid-radial pulse wave velocity was obtained using SphygmoCor®. Heritability analysis (h2, expressed as %) using Sequential Oligogenic Linkage Analysis Routines was performed on the entire cohort and adjusted for age, sex, race, body-mass index, smoking, and mean arterial pressure. Data are presented as mean±SE. Measures of brachial artery diameter (h2=25±9%, P=0.001), lumen diameter (h2=55±9%, P<0.001), intima-media thickness (h2=29±13%, P=0.014), diameter distensibility (h2=28±7%, P<0.001), cross-sectional distensibility (h2=27±7%, P<0.001), and pulse wave velocity (h2=26±9%, P<0.001) were significantly heritable. Flow-mediated dilation and incremental elastic modulus were not significantly heritable. Similar associations were observed in analysis restricted to siblings and complete Trios (mother, father, and child).These data show that the majority of noninvasive measures of vascular structure and function are heritable, suggesting that measurement of these subclinical risk factors in parents may be helpful in assessing childhood risk for future cardiovascular disease.
| S-EPMC5523771 | biostudies-other
Project description:Mapping the Human Connectome: Structure, Function, and Heritability
| PRJNA384837 | ENA
Project description:The cytochrome P450 (P450) enzymes are the predominant enzyme system involved in human drug metabolism. Alterations in the expression and/or activity of these enzymes result in changes in pharmacokinetics (and consequently the pharmacodynamics) of drugs that are metabolized by this set of enzymes. Apart from changes in activity as a result of drug-drug interactions (by P450 induction or inhibition), the P450 enzymes can exhibit substantial interindividual variation in basal expression and/or activity, leading to differences in the rates of drug elimination and response. This interindividual variation can result from a myriad of factors, including genetic variation in the promoter or coding regions, variation in transcriptional regulators, alterations in microRNA that affect P450 expression, and ontogenic changes due to exposure to xenobiotics during the developmental and early postnatal periods. Other than administering a probe drug or cocktail of drugs to obtain the phenotype or conducting a genetic analysis to determine genotype, methods to determine interindividual variation are limited. Phenotyping via a probe drug requires exposure to a xenobiotic, and genotyping is not always well correlated with phenotype, making both methodologies less than ideal. This article describes recent work evaluating the effect of some of these factors on interindividual variation in human P450-mediated metabolism and the potential utility of endogenous probe compounds to assess rates of drug metabolism among individuals.
| S-EPMC4767386 | biostudies-literature
Project description:AimsThe aim of this study was to investigate the heritability as well as genetic and environmental correlations of left ventricular (LV) structural and functional traits in complex pedigrees of a Caucasian population.Methods and resultsWe randomly recruited 459 white European subjects from 52 families (50% women; mean age 45 years). LV structure was measured by M-mode and 2D echocardiography and LV function was measured by conventional Doppler and tissue Doppler imaging (TDI). Other measurements included blood pressure, anthropometric, and biochemical measurements. We estimated the heritability of LV traits while adjusting for covariables, including sex, age, body height and weight, systolic and diastolic blood pressures, and heart rate. With full adjustment, heritability of LV mass was 0.23 (P= 0.025). The TDI-derived mitral annular velocities Ea and Aa showed moderate heritability (h(2)= 0.36 and 0.53, respectively), whereas the mitral inflow A peak had weak heritability (h(2) = 0.25) and the E peak was not heritable (h(2) = 0.11). We partitioned the total phenotypic correlation when it reached significance, into a genetic and an environmental component. The genetic correlations were 0.61 between the E and Ea peaks and 0.90 between the A and Aa peaks.ConclusionOur study demonstrated moderate heritability for LV mass as well as the mitral annular Ea and Aa peaks. We also found significant genetic correlations between the E and Ea peaks and between the A and Aa peaks. Our current findings support the ongoing research to map and detect genetic variants that contribute to the variation in LV mass and other LV structural and functional phenotypes.
| S-EPMC3106286 | biostudies-literature
Project description:Variability in hepatic CYP3A4 cannot be explained by common CYP3A4 coding variants. We previously identified polymorphisms in pregnane X receptor (PXR) and ATP-binding cassette subfamily B member 1 (ABCB1) associated with CYP3A4 mRNA levels in small cohorts of human livers. However, the relative contributions of these genetic variations or of polymorphisms in other CYP3A4 regulators to variable CYP3A4 expression were not known. We phenotyped livers from white donors (n = 128) by quantitative real-time polymerase chain reaction for expression of CYP3A4, CYP3A5, and CYP3A7 and nine transcriptional regulators, coactivators, and corepressors. We resequenced hepatic nuclear factor-3-beta (HNF3beta, FoxA2), HNF4alpha, HNF3gamma (FoxA3), nuclear receptor corepressor 2 (NCoR2), and regions of the CYP3A4 promoter and genotyped informative single-nucleotide polymorphisms in PXR and ABCB1 in the same livers. CYP3A4 mRNA was positively correlated with PXR and FoxA2 and negatively correlated with NCoR2 mRNA. A common silent polymorphism and a polymorphic trinucleotide (CCT) repeat in FoxA2 were associated with CYP3A4 expression. The transcriptional activity of the FoxA2 polymorphic CCT repeat alleles (wild-type, n = 14 and variant, n = 13, 15, and 19) when assayed by luciferase reporter transactivation assays was greatest for the wild-type repeat, with deviations from this number having decreased transcriptional activity. This corresponded with higher expression of FoxA2 mRNA and its targets PXR and CYP3A4 in human livers with (CCT) n = 14 genotypes. Multiple linear regression analysis was used to quantify the contributions of selected genetic polymorphisms to variable CYP3A4 expression. This approach identified sex and polymorphisms in FoxA2, HNF4alpha, FoxA3, PXR, ABCB1, and the CYP3A4 promoter that together explained as much as 24.6% of the variation in hepatic CYP3A4 expression.
| S-EPMC2835441 | biostudies-literature
Project description:The key problem in human infectious diseases was posed at the turn of the 20th century: their pathogenesis. For almost any given virus, bacterium, fungus, or parasite, life-threatening clinical disease develops in only a small minority of infected individuals. Solving this infection enigma is important clinically, for diagnosis, prognosis, prevention, and treatment. Some microbes will inevitably remain refractory to, or escape vaccination, or chemotherapy, or both. The solution also is important biologically, because the emergence and evolution of eukaryotes alongside more rapidly evolving prokaryotes, archaea, and viruses posed immunological challenges of an ecological and evolutionary nature. We need to study these challenges in natural, as opposed to experimental, conditions, and also at the molecular and cellular levels. According to the human genetic theory of infectious diseases, inborn variants underlie life-threatening infectious diseases. Here I review the history of the field of human genetics of infectious diseases from the turn of the 19th century to the second half of the 20th century. This paper thus sets the scene, providing the background information required to understand and appreciate the more recently described monogenic forms of resistance or predisposition to specific infections discussed in a second paper in this issue.
| S-EPMC4697415 | biostudies-other
Project description:Genome-wide association studies have demonstrated significant links between human brain structure and common DNA variants. Similar studies with rodents have been challenging because of smaller brain volumes. Using high field MRI (9.4 T) and compressed sensing, we have achieved microscopic resolution and sufficiently high throughput for rodent population studies. We generated whole brain structural MRI and diffusion connectomes for four diverse isogenic lines of mice (C57BL/6J, DBA/2J, CAST/EiJ, and BTBR) at spatial resolution 20,000 times higher than human connectomes. We measured narrow sense heritability (h2) I.e. the fraction of variance explained by strains in a simple ANOVA model for volumes and scalar diffusion metrics, and estimates of residual technical error for 166 regions in each hemisphere and connectivity between the regions. Volumes of discrete brain regions had the highest mean heritability (0.71 ± 0.23 SD, n = 332), followed by fractional anisotropy (0.54 ± 0.26), radial diffusivity (0.34 ± 0.022), and axial diffusivity (0.28 ± 0.19). Connection profiles were statistically different in 280 of 322 nodes across all four strains. Nearly 150 of the connection profiles were statistically different between the C57BL/6J, DBA/2J, and CAST/EiJ lines. Microscopic whole brain MRI/DTI has allowed us to identify significant heritable phenotypes in brain volume, scalar DTI metrics, and quantitative connectomes.
| S-EPMC8442986 | biostudies-literature
Project description:The McGurk illusion is experienced to various degrees among the general population. Previous studies have implicated the left superior temporal sulcus (STS) and auditory cortex (AC) as regions associated with this interindividual variability. We sought to further investigate the neurophysiology underlying this variability using a variant of the McGurk illusion design. Electroencephalography (EEG) was recorded while human subjects were presented with videos of a speaker uttering the consonant-vowels (CVs) /ba/ and /fa/, which were mixed and matched with audio of /ba/ and /fa/ to produce congruent and incongruent conditions. Subjects were also presented with unimodal stimuli of silent videos and audios of the CVs. They responded to whether they heard (or saw in the silent condition) /ba/ or /fa/. An illusion during the incongruent conditions was deemed successful when individuals heard the syllable conveyed by mouth movements. We hypothesized that individuals who experience the illusion more strongly should exhibit more robust desynchronization of alpha (7-12?Hz) at fronto-central and temporal sites, emphasizing more engagement of neural generators at the AC and STS. We found, however, that compared to weaker illusion perceivers, stronger illusion perceivers exhibited greater alpha synchronization at fronto-central and posterior temporal sites, which is consistent with inhibition of auditory representations. These findings suggest that stronger McGurk illusion perceivers possess more robust cross-modal sensory gating mechanisms whereby phonetic representations not conveyed by the visual system are inhibited, and in turn reinforcing perception of the visually targeted phonemes.
| S-EPMC6716985 | biostudies-literature