Background: While there is clear evidence of sex-specific global and regional methylation patterns, these have yet to be examined within the context of central adiposity. We conducted a ...methylation-wide association study (MWAS) to identify cytosine-phosphate-guanine (CpG) sites that exhibit sex-specific associations with waistcircumference (WC), WC-to-hip ratio (WHR), and WC-to-height ratio (WHtR). Our study included African American (AA) adults in the Atherosclerosis Risk in Communities study (ARIC; 1,702 females; 982 males) with whole blood Illumina 450K genome-wide methylation typing data. Methods: We adjusted CpG beta values for batch effects and white blood cell proportions and used the resulting residuals in subsequent analyses. We performed sex-stratified MWAS analyses with waist traits using linear regression (or mixed model for family studies), adjusted for age, education, BMI, smoking, center, and 10 genetic principal components. Using sex-stratified results, we estimated sexinteraction methylation effects (INT) and main+interaction effects (JOINT), respectively. CpGs that reached suggestive significance (Pjoint or PINT < 1 x 10-6) were brought forward for generalization in an independent sample of European descent (EUD) adults (2,777 women; 2,299 men) from ARIC and Framingham Heart Study (FHS). Results: We identified a total of 43 non-overlapping CpGs (8 WC, 35 WHR, 20 WHtR) in our discovery analyses with evidence of sexinteraction. Of the 43 CpGs, 5 of them (cg06500161 near ABCG1, cg19693031 near TXNIP, cg00574958 near CPT1A, cg06192883 near MYO5C, cg23580000 near ADCY7) met Bonferroni-corrected significance in our generalization analyses for one or more waist traits (3 WC, 5 WHR, and 2 WHtR) in the JOINT model, including 2 CpGs (cg19693031 near TXNIP and cg06500161 in ABCG1) also significant for the INT model. Both of these CpG sites that displayed significant in INT had stronger effects in women compared to men (i.e., cg19693031 displayed ~4x effect in women (Beta = -0.23) compared to men (Beta = -0.06) for WHR) in our generalization. Conclusions: These findings underscore the importance of accounting for sex in MWAS, as differences in methylation of CpG sites in TXNIP and ABCG1 (these genes involved in glucose and lipid homeostasis) between sexes may help to explain sex differences in downstream diseases linked to obesity.
Background: Stimulation of energy expenditure (EE) is a common strategy in obesity treatment, and EE has several components, including that derived from spontaneous physical activity (SPA), which ...produces non-exercise activity thermogenesis (NEAT). The neuropeptide orexin A increases SPA and NEAT in several animal models. The New Zealand Obese (NZO) mouse is a polygenic animal model of obesity and diabetes, but orexin action in these mice has not been examined. Our aim was to evaluate the potential therapeutic effect of a novel orexin agonist (RTIOXA-47) for the treatment of obesity in NZO mice. We hypothesized that peripheral RTIOXA-47 administration increases SPA and attenuates obesity in NZO mice. Methods: To test this, male and female C57BL/6 WT and NZO mice (n = 24) were housed individually and randomly assigned to treatment with saline or RTIOXA47 (40 mg/kg), administered via intraperitoneal injection 5 days per week for five weeks. The current N = 3 per species, sex and treatment, but an additional cohort is in progress. Body weight (BW) and food intake (FI) were recorded weekly. Body composition (BC) and 24-hour SPA and EE were measured before and after treatment. To analyze the data, Generalized Estimated Equations (GEE) were performed followed by Bonferroni post hoc test. Significance was set at p<0.05. Results: A significant sex·strain·time·treatment interaction was observed for BW, FI, SPA, EE and fat mass (FM). Significant sex differences were seen in both NZO vs. WT across all variables. A benefit of RTIOXA-47 was seen in WT males and NZO females as both sets of treated mice had significantly lower BW and FM compared with their respective non-treated group at studys end (p <0.05). For FI, the same was observed, but only in WT females (treated < non-treated). Conclusions: These preliminary findings suggest that RTIOXA47 may help reduce BW and FM, but additional statistical power gained by inclusion of the next cohort of mice will help expand and solidify these results.
The primary aims of this literature audit were to, firstly, understand the extent of female representation in the participant populations of EIGD research; and secondly, within the studies conducted ...with females, to assess the quality of data pertaining to menstrual (and thus hormone) status of participants. Additionally, within the literature, female data (demographics and results) were typically combined with male data and reported together. ...not only is there an underrepresentation of females to begin with, but what data there is, is subsumed within the overall mean of the combined data making future analysis of sex-disaggregated data (e.g., meta-analyses) impossible. There is a need for a greater quantity of high quality data using rigorous methodology to ascertain and report menstrual status of female athletes, as well as sex-disaggregation of data, if we are to understand potential sex differences in EIGD.
Introduction
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by social and communication deficits and restricted and repetitive or stereotyped behaviours. The prevalence ...of ASD has been thought to be higher in men, which may reflect aspects of the own aetiology of the disorder. Still, it may also be associated with misdiagnosis or missed diagnosis of females with autism due to specific phenotypic traits.
Objectives
To explore the differences between sex/gender in autism’s clinical presentation.
Methods
Non-systematic literature review using the most relevant papers found on PubMed and Google Scholar using the following keywords: “autism spectrum disorder”, “gender differences”, and “autistic women”.
Results
Autistic women seem to have a “camouflage” phenomenon, characterized by a high level of functioning, less unusual play or restricted interests, better socio-emotional reciprocity and coping behaviours. Therefore, women with ASD commonly have an anteriority of multiple diagnoses, which delays their access to the support and care they need.
Conclusions
Professionals must be aware of the sex/gender clinical differences to prevent the misdiagnosis or missed diagnosis of females with autism. Moreover, the current clinical criteria used to diagnose ASD may underserve the female population and deserve to be reviewed.
Disclosure of Interest
None Declared
Abstract
Introduction
Studies have shown that sleep affects working memory (WM) improvement, but specific electrophysiological features are unclear (Sattari et al., 2019; MacDonald et al., 2018). In ...addition, sex differences have been found in both sleep and working memory (Mong, 2016; Harness, 2008). The goal of this study is to identify sex differences in EEG correlates of working memory over a night of sleep.
Methods
Sixty-three healthy (33 females), college-aged adults without sleep disorder were enrolled. A 32-channel electroencephalogram (EEG) cap was used to record brain activity during sleep. Operation span (OS) task was used to evaluate WM performance. Participants reported to the laboratory in the evening, performed OS before sleep (test1) and after sleep (test2). Trials were divided into easy and hard trials based on the number of letters subjects had to recall. A repeated-measure analysis of variance was conducted to examine the effects of time and trial difficulty. Paired-sample t-tests between test 1 and test 2 were conducted for males and females. Pearson’s correlations were examined between WM performance at test 1 and the difference score between test 1 and test 2 and EEG frequency bands. The Benjamini–Hochberg method was used to control for multiple comparisons.
Results
There was an increase in performance across the night in WM hard trials across all subjects (F(1,62)=4.86, p=0.03), no effect for easy trials (p>0.05). Females, but not males, showed a significant decrease in easy trials (t62= 2.40, p=0.02), while both males and females showed improvement in hard trials across the night. Females showed a positive correlation between test 1 hard trials and slow sigma, delta, slow oscillation in stage 3, this correlation is not seen in males. No correlations between overnight improvement and EEG bands were found.
Conclusion
Consistent with previous studies, participants showed better memory performance over a night of sleep, and the WM performance was associated with slow wave activity in females. Slow sigma also plays a role in the WM performance for females, indicating a possible role of sleep spindles. These associations were not shown in males, suggesting sex hormones mediate sleep’s impact on WM performance.
Support (if any):
Abstract
Introduction
The current study investigated whether insufficient sleep (<7 hrs.) explains differences in 10-year CVD risk, using Framingham risk (FRS) and Reynolds risk (RRS) scores, between ...blacks and whites and characterized risk and protective CVD risk profiles.
Methods
Using the Sleep Heart Health Study (SHHS) (N=6,441) data, we investigated the independent role of insufficient sleep in explaining differences in 10-years CVD between blacks and whites via a proportional odds model of four 10-year CVD risk groups: low (<5%), low-medium (5% to <10%), medium-high (10% to <20%) and high (≥20%), adjusting for age, sex, and apnea-hypopnea index (AHI). We performed two levels of cluster analyses; via hierarchical cluster algorithm with entire sample (Level 1), and latent profiles in the low (protective profiles) and high (risk profiles) CVD risk groups (Level 2) to determine overall CVD risk, and risk and protective CVD profiles.
Results
Blacks had a higher prevalence of smoking behavior, diabetes, mean systolic blood pressure, body mass index, total cholesterol compared to whites. Conversely, whites had a higher mean HDL cholesterol, sleep hours, and sleep efficiency compared to blacks. Men had higher 10-year CVD risk than women. AHI and race/ethnicity-sleep interaction were positively associated, while sleep was negatively associated with FRS and RRS. Across all CVD risk groups, whites who slept less than 5.5 hrs. had a higher CVD risk and those who slept more than 6.5 hrs. had a lower CVD risk compared to blacks. In Level 1 cluster analyses, we found two clusters: Cluster 1 (n= 3233): 6.17 sleep hours, apnea-index 11.84, age 59, SBP 125.43, total cholesterol 209, HDL 51.39, BMI 29.03, and slightly more than 50% female; and Cluster 2 (n=1657): 5.61 sleep hours, apnea-index 13.41, age 74, SBP 131, total cholesterol 204, HDL 50.30, BMI 26.45, and slightly less than 50% female. In Level 2 cluster analyses, we found two profiles within the low and high CVD risk groups.
Conclusion
These findings suggest that blacks may not receive full protection from long-term CVD risk with longer sleep duration, as their white counterparts.
Support
K01HL135452, R01MD007716, R01HL142066, K07AG052685
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