| 1. |
- Cruz, Raquel, et al.
(author)
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Novel genes and sex differences in COVID-19 severity
- 2022
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In: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
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Journal article (peer-reviewed)abstract
- Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
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| 2. |
- Ortega, Francisco B., et al.
(author)
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Effects of an Exercise Program on Brain Health Outcomes for Children With Overweight or Obesity The ActiveBrains Randomized Clinical Trial
- 2022
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In: JAMA Network Open. - : American Medical Association. - 2574-3805. ; 5:8
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Journal article (peer-reviewed)abstract
- IMPORTANCE Pediatric overweight and obesity are highly prevalent across the world, with implications for poorer cognitive and brain health. Exercise might potentially attenuate these adverse consequences. OBJECTIVES To investigate the effects of an exercise program on brain health indicators, including intelligence, executive function, academic performance, and brain outcomes, among children with overweight or obesity and to explore potential mediators and moderators of the main effects of exercise. DESIGN, SETTING, AND PARTICIPANTS All preexercise and postexercise data for this 20-week randomized clinical trial of 109 children aged 8 to 11 years with overweight or obesity were collected from November 21, 2014, to June 30, 2016, with neuroimaging data processing and analyses conducted between June 1, 2017, and December 20, 2021. All 109 children were included in the intention-to-treat analyses; 90 children (82.6%) completed the postexercise evaluation and attended 70% or more of the recommended exercise sessions and were included in per-protocol analyses. INTERVENTIONS All participants received lifestyle recommendations. The control group continued their usual routines, whereas the exercise group attended a minimum of 3 supervised 90-minute sessions per week in an out-of-school setting. MAIN OUTCOMES AND MEASURES Intelligence, executive function (cognitive flexibility, inhibition, and working memory), and academic performance were assessed with standardized tests, and hippocampal volume was measured with magnetic resonance imaging. RESULTS The 109 participants included 45 girls (41.3%); participants had a mean (SD) body mass index of 26.8 (3.6) and a mean (SD) age of 10.0 (1.1) years at baseline. In per-protocol analyses, the exercise intervention improved crystallized intelligence, with the exercise group improving from before exercise to after exercise (mean z score, 0.62 [95% CI, 0.44-0.80]) compared with the control group (mean z score, -0.10 [95% CI, -0.28 to 0.09]; difference between groups, 0.72 SDs [95% CI, 0.46-0.97]; P < .001). Total intelligence also improved significantly more in the exercise group (mean z score, 0.69 [95% CI, 0.48-0.89]) than in the control group (mean z score, 0.07 [95% CI, -0.14 to 0.28]; difference between groups, 0.62 SDs [95% CI, 0.31-0.91]; P < .001). Exercise also positively affected a composite score of cognitive flexibility (mean z score: exercise group, 0.25 [95% CI, 0.05-0.44]; control group, -0.17 [95% CI, -0.39 to 0.04]; difference between groups, 0.42 SDs [95% CI, 0.13-0.71]; P = .005). These main effects were consistent in intention-to-treat analyses and after multiple-testing correction. There was a positive, small-magnitude effect of exercise on total academic performance (mean z score: exercise group, 0.31 [95% CI, 0.18-0.44]; control group, 0.10 [95% CI, -0.04 to 0.24]; difference between groups, 0.21 SDs [95% CI, 0.01-0.40]; P = .03), which was partially mediated by cognitive flexibility. Inhibition, working memory, hippocampal volume, and other brain magnetic resonance imaging outcomes studied were not affected by the exercise program. The intervention increased cardiorespiratory fitness performance as indicated by longer treadmill time to exhaustion (mean z score: exercise group, 0.54 [95% CI, 0.27-0.82]; control group, 0.13 [95% CI, -0.16 to 0.41]; difference between groups, 0.42 SDs [95% CI, 0.01-0.82]; P = .04), and these changes in fitness mediated some of the effects (small percentage of mediation [approximately 10%-20%]). The effects of exercise were overall consistent across the moderators tested, except for larger improvements in intelligence among boys compared with girls. CONCLUSIONS AND RELEVANCE In this randomized clinical trial, exercise positively affected intelligence and cognitive flexibility during development among children with overweight or obesity. However, the structural and functional brain changes responsible for these improvements were not identified.
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| 3. |
- Torres-Lopez, Lucia V, et al.
(author)
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Associations of Sleep-Related Outcomes with Behavioral and Emotional Functioning in Children with Overweight/Obesity
- 2022
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In: The Journal of Pediatrics. - : Elsevier. - 0022-3476 .- 1097-6833. ; 246, s. 170-178.e2
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Journal article (peer-reviewed)abstract
- Objective To evaluate the associations of parent-reported sleep-disordered breathing (SDB) and device-assessed sleep behaviors with behavioral and emotional functioning in pediatric patients with overweight/obesity. Study design A total of 109 children with overweight/obesity (mean age, 10.0 +/- 1.1 years) were included in this cross-sectional study. We used the Spanish version of the Pediatric Sleep Questionnaire (PSQ) to assess SDB and its subscales (ie, snoring, daytime sleepiness, and inattention/hyperactivity). Device-assessed sleep behaviors (ie, wake time, sleep onset time, total time in bed, total sleep time, and waking after sleep onset) were estimated using wrist-worn accelerometers. We used the Behavior Assessment System for Children, second edition to assess behavioral and emotional functioning (ie, clinical scale: aggressiveness, hyperactivity, behavior problems, attention problems, atypicality, depression, anxiety, retreat, and somatization; adaptive scale: adaptability, social skills, and leadership). Results SDB was positively associated with all clinical scale variables (all beta > 0.197, P <=.041) and with lower adaptability and leadership (all beta < -0.226, P < .021). Specifically, the PSQ subscale relating to daytime sleepiness was associated with higher attention problems, depression, anxiety, and retreat (all beta > 0.196, P .045) and lower adaptability (beta = -0.246, P = .011). The inattention/hyperactivity subscale was significantly associated with the entire clinical and adaptive scales (all beta > vertical bar 0.192 vertical bar, P <= .046) except for somatization. The snoring subscale and device-assessed sleep behaviors were not related to any behavioral or emotional functioning variables. Conclusions Our study suggests that SDB symptoms, but not device-assessed sleep behaviors, are associated with behavioral and emotional functioning in children with overweight/obesity. Specifically, daytime sleepiness, a potential SDB symptom, was related to higher attention problems, depression, anxiety, and retreat and lower adaptability.
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| 4. |
- Torres-Lopez, Lucia V, et al.
(author)
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Does sleep-disordered breathing add to impairments in academic performance and brain structure usually observed in children with overweight/obesity?
- 2022
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In: European Journal of Pediatrics. - : Springer. - 0340-6199 .- 1432-1076. ; 181, s. 2055-2065
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Journal article (peer-reviewed)abstract
- Approximately 4-11% of children suffer from sleep-disordered breathing (SDB), and children with obesity are at increased risk. Both obesity and SDB have been separately associated with poorer brain health, yet whether SDB severity affects brain health in children with obesity remains unanswered. This study aimed to examine associations of SDB severity with academic performance and brain structure (i.e., total brain and gray and white matter volumes and gray matter volume in the hippocampus) in children with overweight/obesity. One hundred nine children aged 8-12 years with overweight/obesity were included. SDB severity and its subscales (i.e., snoring, daytime sleepiness, and inattention/hyperactivity) were evaluated via the Pediatric Sleep Questionnaire (PSQ), and academic performance was evaluated with the Woodcock-Munoz standardized test and school grades. Brain structure was assessed by magnetic resonance imaging. SDB severity was not associated with academic performance measured by the standardized test (all vertical bar beta vertical bar> 0.160, P > 0.076), yet it was associated with the school grade point average (beta = -0.226, P = 0.007) and natural and social science grades (beta = -0.269, P = 0.024). Intention/hyperactivity seemed to drive these associations. No associations were found between SDB severity and the remaining school grades (all beta < -0.188, P > 0.065) or brain volumes (all P > 0.05). Conclusion: Our study shows that SDB severity was associated with lower school grades, yet it was not associated with the standardized measurement of academic performance or with brain volumes in children with overweight/obesity. SDB severity may add to academic problems in children beyond the effects contributed by overweight/obesity status alone.
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