Joint models reveal genetic architecture of pubertal stage transitions and their association with BMI in admixed Chilean population.

Early or late pubertal onset can lead to disease in adulthood, including cancer, obesity, type 2 diabetes, metabolic disorders, bone fractures, and psychopathologies. Thus, knowing the age at which puberty is attained is crucial as it can serve as a risk factor for future diseases. Pubertal development is divided into five stages of sexual maturation in boys and girls according to the standardized Tanner scale. We performed genome-wide association studies (GWAS) on the "Growth and Obesity Chilean Cohort Study" cohort composed of admixed children with mainly European and Native American ancestry. Using joint models that integrate time-to-event data with longitudinal trajectories of body mass index (BMI), we identified genetic variants associated with phenotypic transitions between pairs of Tanner stages. We identified $42$ novel significant associations, most of them in boys. The GWAS on Tanner $3\rightarrow 4$ transition in boys captured an association peak around the growth-related genes LARS2 and LIMD1 genes, the former of which causes ovarian dysfunction when mutated. The associated variants are expression and splicing Quantitative Trait Loci regulating gene expression and alternative splicing in multiple tissues. Further, higher individual Native American genetic ancestry proportions predicted a significantly earlier puberty onset in boys but not in girls. Finally, the joint models identified a longitudinal BMI parameter significantly associated with several Tanner stages' transitions, confirming the association of BMI with pubertal timing.

Exposure to obesogenic endocrine disrupting chemicals and obesity among youth of Latino or Hispanic origin in the United States and Latin America: A lifecourse perspective.

Following a 2019 workshop led by the Center for Global Health Studies at the Fogarty International Center on the topic of childhood obesity prevention and research synergies transpiring from cross-border collaborations, we convened a group of experts in the United States and Latin America to conduct a narrative review of the epidemiological literature on the role of obesogenic endocrine disrupting chemicals (EDCs) in the etiology of childhood obesity among Latino youth in the United States and Latin America. In addition to summarizing and synthesizing results from research on this topic published within the last decade, we place the findings within a lifecourse biobehavioral framework to aid in identification of unique exposure-outcome relationships driven by both biological and behavioral research, identify inconsistencies and deficiencies in current literature, and discuss the role of policy regulations, all with the goal of identifying viable avenues for prevention of early life obesity in Latino/Hispanic populations.

Antinociceptive activity of the Psidium brownianum Mart ex DC. leaf essential oil in mice.

Chronic pain management has several adverse effects and research looking for new and effective pain management drugs posing lower undesirable effects is necessary. Given the above, the pharmacological investigation of medicinal plants significantly contributes to the dissemination of plant-derived therapeutics. The aim of this study was to evaluate the antinociceptive activity of the Psidium brownianum Mart ex DC. leaf essential oil (PBEO) and the participation of the opioid pathway in this effect in mice. Swiss Mus musculus male mice were tested using acute nociception models (acetic acid induced abdominal contortions, formalin, capsaicin and hot plate tests). The possible myorelaxant action of the PBEO was tested using the rotarod test. The essential oil reduced animal nociception in chemical and heat models, with this action being devoid of a myorelaxant effect. Naloxone (2 mg/kg, intraperitoneally - i.p.) partially antagonized the PBEO activity, possibly acting via opioid receptors. The results obtained provide evidence that the traditional Psidium brownianum use may be effective for pain treatment.

Genetic Variation of Follicle-Stimulating Hormone Action Is Associated With Age at Testicular Growth in Boys.

Context: Although genetic factors play a pivotal role in male pubertal timing, genome-wide association studies have identified only a few loci. Genetic variation of follicle-stimulating hormone (FSH) action affects adult reproductive parameters and female pubertal timing. Objective: To investigate whether genetic variation affecting FSH action is associated with onset of puberty in boys. Design: Cross-sectional and longitudinal study of two cohorts of healthy boys. Setting: This was a population-based study. Patients or Other Participants: Danish (n = 1130) and Chilean (n = 424) boys were followed through puberty and genotyped for FSHB c.-211G>T, FSHR c.-29A>G, and FSHR c.2039G>A. Main Outcome Measures: Clinical pubertal staging including orchidometry, anthropometry, and serum gonadotropin levels. Results: Although the cohorts differed markedly (e.g., body composition and genotype frequencies), genetic variation affecting FSH production (FSHB c.-211G>T) was associated with age at pubertal onset, as assessed by testicular enlargement, in both cohorts. The effect appeared further modified by coexistence of genetic variation affecting FSH sensitivity (FSHR c.-29G>A): After correcting for body mass index (BMI), boys with a ligand-receptor variant combination resulting in weak FSH action (i.e., FSHB c.-211GT/TT and FSHR c.-29AA) entered puberty 0.64 years [95% confidence interval (CI), 0.12 to 1.17 years; Denmark] and 0.94 years (95% CI, 0.00 to 1.88 years; Chile) later than boys with the most effective FSH action. Effects explained 1.7% (Denmark) and 1.5% (Chile) of the variance. In addition, BMI z score was negatively associated with pubertal timing (ß = -0.35 years in both cohorts), explaining 17.2% (Denmark) and 7.2% (Chile) of the variance. Conclusion: In two ethnically distinct populations, we independently identified an association of two genetic loci with male pubertal timing.

Exposición a químicos disruptores endócrinos obesogénicos y obesidad en niños y jóvenes de origen latino o hispano en Estados Unidos y Latinoamérica: una perspectiva del curso de la vida.

En el 2019, en seguimiento a un taller dirigido por el Global Health Studies del Fogarty International Center sobre el tema de la prevención de la obesidad infantil y las sinergias de investigación que surgen a través de las colaboraciones transfronterizas, convocamos a un grupo de expertos de Estados Unidos y Latinoamérica para que realizaran una revisión narrativa de la literatura epidemiológica sobre el papel obesogénico de los químicos disruptores endócrinos (EDC, por sus siglas en inglés) en la etiología de la obesidad infantil entre la juventud latina de Estados Unidos y Latinoamérica. Además de resumir y sintetizar los resultados de las investigaciones sobre este tema publicados en la última década, contextualizamos los hallazgos dentro de un marco bioconductual de curso de vida para identificar relaciones exposición-desenlace impulsadas por resultados de investigación, identificar inconsistencias y deficiencias de la literatura actual, y discutir el papel de las regulaciones políticas, todo con el objetivo de identificar posibles vías para la prevención temprana de la obesidad en las poblaciones hispanas/latinas.