A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10⁻⁸) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10⁻¹⁰) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.

Background—: The American Heart Association (AHA) defined a new concept, cardiovascular health, and determined metrics needed to monitor it over time as part of its 2020 Impact Goal definition. Ideal cardiovascular health is defined by the presence of both ideal health behaviors and ideal health factors. The applicability of this concept to a cohort of children and its relationship with cardiometabolic outcomes in adulthood has not been reported. Methods and Results—: The sample comprised 856 participants aged 12 to 18 years (mean age 15.0 years) from the Cardiovascular Risk in Young Finns Study cohort. Participants were followed up for 21 years since baseline (1986) and had data available concerning health factors and behaviors in childhood and cardiometabolic outcomes in adulthood (2007). The number of ideal cardiovascular health metrics present in childhood was associated with reduced risk of hypertension (odds ratio [95% confidence interval] 0.66 [0.52–0.85], P <0.001), metabolic syndrome (0.66 [0.52–0.77], P <0.001), high low-density lipoprotein cholesterol (0.66 [0.52–0.85], P =0.001), and high-risk carotid artery intima-media thickness (0.75 [0.60–0.94], P =0.01) in adulthood. All analyses were age and sex adjusted, and the results were not altered after additional adjustment with socioeconomic status. Conclusions—: The number of ideal cardiovascular health metrics present in childhood predicts subsequent cardiometabolic health in adulthood. Our findings suggest that pursuit of ideal cardiovascular health in childhood is important to prevent cardiometabolic outcomes in adulthood.

Recent studies suggest that exercise alters the gut microbiome. We determined whether six-weeks endurance exercise, without changing diet, affected the gut metagenome and systemic metabolites of overweight women. Previously sedentary overweight women (n = 19) underwent a six-weeks endurance exercise intervention, but two were excluded due to antibiotic therapy. The gut microbiota composition and functions were analyzed by 16S rRNA gene amplicon sequencing and metagenomics. Body composition was analyzed with DXA X-ray densitometer and serum metabolomics with NMR metabolomics. Total energy and energy-yielding nutrient intakes were analyzed from food records using Micro-Nutrica software. Serum clinical variables were determined with KONELAB instrument. Soluble Vascular Adhesion Protein 1 (VAP-1) was measured with ELISA and its' enzymatic activity as produced hydrogen peroxide. The exercise intervention was effective, as maximal power and maximum rate of oxygen consumption increased while android fat mass decreased. No changes in diet were observed. Metagenomic analysis revealed taxonomic shifts including an increase in Akkermansia and a decrease in Proteobacteria. These changes were independent of age, weight, fat % as well as energy and fiber intake. Training slightly increased Jaccard distance of genus level β-diversity. Training did not alter the enriched metagenomic pathways, which, according to Bray Curtis dissimilarity analysis, may have been due to that only half of the subjects' microbiomes responded considerably to exercise. Nevertheless, tranining decreased the abundance of several genes including those related to fructose and amino acid metabolism. These metagenomic changes, however, were not translated into major systemic metabolic changes as only two metabolites, phospholipids and cholesterol in large VLDL particles, decreased after exercise. Training also decreased the amine oxidase activity of pro-inflammatory VAP-1, whereas no changes in CRP were detected. All clinical blood variables were within normal range, yet exercise slightly increased glucose and decreased LDL and HDL. In conclusion, exercise training modified the gut microbiome without greatly affecting systemic metabolites or body composition. Based on our data and existing literature, we propose that especially Akkermansia and Proteobacteria are exercise-responsive taxa. Our results warrant the need for further studies in larger cohorts to determine whether exercise types other than endurance exercise also modify the gut metagenome.

Background—: In the Special Turku Coronary Risk Factor Intervention Project for Children (STRIP) study, repeated dietary counseling introduced in infancy and maintained until 20 years of age has led to lower intakes of saturated fat and serum low-density lipoprotein cholesterol. In this study, we examined prospectively the intervention effects on the ideal cardiovascular health concept recently described by the American Heart Association. Additionally, we investigated the association between the concept and vascular intima-media thickness and elasticity in adolescence. Methods and Results—: In adolescents participating in the longitudinal, randomized, atherosclerosis-prevention STRIP study, complete data on ideal cardiovascular health metrics were available at 15 (n=394), 17 (n=376), and 19 (n=298) years of age. Aortic intima-media thickness and elasticity were measured with ultrasonography at the same ages. None of the adolescents had all 7 ideal cardiovascular health metrics. At least 5 ideal metrics was found in 60.2%, 45.5%, and 34.2% of the adolescents at 15, 17, and 19 years of age, respectively. Adolescents in the control group had an increased risk of low ideal cardiovascular health (≤3 metrics) compared with the intervention adolescents (risk ratio=1.35; 95% confidence interval=1.04–1.77). The number of ideal cardiovascular health metrics was inversely associated with aortic intima-media thickness ( P 85th percentile) was nearly 2-fold in adolescents with a low number of metrics (≤3) compared with those with a higher score (risk ratio=1.78; 95% confidence interval=1.31–2.43). Conclusions—: Ideal cardiovascular health as determined by the AHA can be promoted in adolescents. The ideal cardiovascular health concept is beneficially associated with vascular health already in adolescence, supporting the relevance of targeting these metrics as part of primordial prevention. Clinical Trial Registration—: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00223600