Although hundreds of genome-wide association studies-implicated loci have been reported for adult obesity-related traits, less is known about the genetics specific for early-onset obesity and with only a few studies conducted in non-European populations to date. Searching for additional genetic variants associated with childhood obesity, we performed a trans-ancestral meta-analysis of 30 studies consisting of up to 13 005 cases (≥95th percentile of body mass index (BMI) achieved 2–18 years old) and 15 599 controls (consistently <50th percentile of BMI) of European, African, North/South American and East Asian ancestry. Suggestive loci were taken forward for replication in a sample of 1888 cases and 4689 controls from seven cohorts of European and North/South American ancestry. In addition to observing 18 previously implicated BMI or obesity loci, for both early and late onset, we uncovered one completely novel locus in this trans-ancestral analysis (nearest gene, METTL15). The variant was nominally associated with only the European subgroup analysis but had a consistent direction of effect in other ethnicities. We then utilized trans-ancestral Bayesian analysis to narrow down the location of the probable causal variant at each genome-wide significant signal. Of all the fine-mapped loci, we were able to narrow down the causative variant at four known loci to fewer than 10 single nucleotide polymorphisms (SNPs) (FAIM2, GNPDA2, MC4R and SEC16B loci). In conclusion, an ethnically diverse setting has enabled us to both identify an additional pediatric obesity locus and further fine-map existing loci.

Objective.To determine the optimal cutoff of the homeostasis model assessment-insulin resistance (HOMA-IR) for diagnosis of the metabolic syndrome (MetS) in adolescents and examine whether insulin resistance (IR), determined by this method, was related to genetic, biological, and environmental factors.Methods.In 667 adolescents (16.8 ± 0.3 y), BMI, waist circumference, glucose, insulin, adiponectin, diet, and physical activity were measured. Fat and fat-free mass were assessed by dual-energy X-ray absorptiometry. Family history of type 2 diabetes (FHDM) was reported. We determined the optimal cutoff of HOMA-IR to diagnose MetS (IDF criteria) using ROC analysis. IR was defined as HOMA-IR values above the cutoff. We tested the influence of genetic, biological, and environmental factors on IR using logistic regression analyses.Results.Of the participants, 16% were obese and 9.4 % met criteria for MetS. The optimal cutoff for MetS diagnosis was a HOMA-IR value of 2.6. Based on this value, 16.3% of participants had IR. Adolescents with IR had a significantly higher prevalence of obesity, abdominal obesity, fasting hyperglycemia, and MetS compared to those who were not IR. FHDM, sarcopenia, obesity, and low adiponectin significantly increased the risk of IR.Conclusions.In adolescents, HOMA-IR ≥ 2.6 was associated with greater cardiometabolic risk.

OBJECTIVE: To examine the relationship between gestational age and mental and psychomotor development scores in healthy infants born between 37 and 41 weeks.METHODS: The cohort included 1562 participants enrolled during infancy in an iron deficiency anemia preventive trial in Santiago, Chile. All participants were healthy, full-term (37–41 weeks) infants who weighed 3 kg or more at birth. Development at 12 months was assessed using the Bayley Scales of Infant Development. Using generalized linear modeling, we analyzed the association between gestational age and 1-year-old developmental status, taking into account potential confounders including birth weight percentile, gender, socioeconomic status, the home environment, iron status, and iron supplementation.RESULTS: For each additional week of gestation, the Mental Development Index increased by 0.8 points (95% confidence interval = 0.2–1.4), and the Psychomotor Development Index increased by 1.4 points (95% confidence interval = 0.6–2.1) controlling for birth weight percentile, gender, socioeconomic status, and home environment.CONCLUSIONS: In a large sample of healthy full-term infants, developmental scores obtained using the Bayley Scales of Infant Development at 12 months increased with gestational age (37–41 weeks). There is increasing evidence that birth at 39 to 41 weeks provides developmental advantages compared with birth at 37 to 38 weeks. Because cesarean deliveries and early-term inductions have increased to 40% of all births, consideration of ongoing brain development during the full-term period is an important medical and policy issue.

Objective: To analyse the prevalence of cardiovascular risk factors in healthy adolescents of low to middle socio-economic status and to study the influence of anthropometric, biological and lifestyle factors on the risk of metabolic syndrome (MetS).Design: Cross-sectional study. BMI, waist circumference, blood pressure, fat and lean mass (by dual-energy X-ray absorptiometry), TAG, HDL-cholesterol, glucose, insulin, homeostatic model assessment–insulin resistance index (HOMA-IR), food intake and physical activity were measured. Cardiovascular risk factors were defined using the International Diabetes Federation criteria and insulin resistance using HOMA-IR ≥2·6. Bivariate and multivariate regressions examined the associations between MetS and anthropometric, biological and lifestyle factors.Setting: Observational cohort study including Chilean adolescents, who were part of a follow-up study beginning in infancy.Subjects: Adolescents aged 16–17 years (n667).Results: In the sample, 16·2 % had obesity and 9·5 % had MetS. Low HDL-cholesterol (69·9 %), abdominal obesity (33·3 %) and fasting hyperglycaemia (8·7 %) were the most prevalent cardiovascular risk factors. In males, obesity (OR=3·7; 95 % CI 1·2, 10·8), insulin resistance (OR=3·0; 95 % CI 1·1, 8·2), physical inactivity (OR=2·9; 95 % CI 1·1, 7·7) and sarcopenia (OR=21·2; 95 % CI 4·2, 107·5) significantly increased the risk of MetS. In females, insulin resistance (OR=4·9; 95 % CI 1·9, 12·6) and sarcopenia (OR=3·6; 95 % CI 1·1, 11·9) were significantly associated with MetS.Conclusions: High prevalences of obesity, abdominal obesity, dyslipidaemia, fasting hyperglycaemia and MetS were found in healthy adolescents. In both sexes, sarcopenia and insulin resistance were important risk factors of MetS. Promotion of active lifestyles at the school level and regulation of the sale of energy-dense foods are needed.

This study examines the extent to which iron deficiency in infancy contributes to adverse neurocognitive and educational outcomes in young adulthood directly and indirectly, through its influence on poor verbal cognition and attention problems in childhood. Young adults (N = 1,000, M age = 21.3 years, 52% female; of mixed Spanish and indigenous descent) from working-class families in Santiago, Chile, completed instruments assessing memory, processing speed, mental flexibility, and educational attainment. Iron status was assessed at ages 6, 12, and 18 months, and verbal intelligence, inattention, and sluggish cognitive tempo (SCT) symptoms were assessed at age 10. Results indicated that young adults who had iron-deficiency in infancy had poor executive control at age 21. Severity of iron deficiency during infancy was associated with lower verbal IQ and more frequent inattention and SCT symptoms in childhood, and with lower educational attainment in young adulthood through its effect on inattention. No additional indirect effects were found. Interventions directed toward improving cognitive and attention deficits linked to early-life iron deficiency appear warranted and could alter the course to adult functioning. Further research on the impact of such interventions would be helpful.