Separating the genetics of childhood and adult obesity: a validation study of genetic scores for body mass index in adolescence and adulthood in the HUNT Study.

From a life-course perspective, genetic and environmental factors driving childhood obesity may have a lasting influence on health later in life. However, how obesity trajectories vary throughout the life-course remains unknown. Recently, Richardson et al. created powerful early life and adult gene scores for body mass index (BMI) in a comprehensive attempt to separate childhood and adult obesity. The childhood score was derived using questionnaire-based data administered to adults aged 40-69 regarding their relative body size at age 10, making it prone to recall and misclassification bias. We therefore attempted to validate the childhood and adult scores using measured BMI data in adolescence and adulthood among 66 963 individuals from the HUNT Study in Norway from 1963 to 2019. The predictive performance of the childhood score was better in adolescence and early adulthood, whereas the predictive performance of the adult score was better in adulthood. In the age group 12-15.9 years, the variance explained by the childhood polygenic risk score (PRS) was 6.7% versus 2.4% for the adult PRS. In the age group 24-29.9 years, the variance explained by the adult PRS was 3.9% versus 3.6% for the childhood PRS. Our findings support that genetic factors driving BMI differ at young age and in adulthood. Within the framework of multivariable Mendelian randomization, the validated childhood gene score can now be used to determine the consequence of childhood obesity on later disease.

Genetic associations with temporal shifts in obesity and severe obesity during the obesity epidemic in Norway: A longitudinal population-based cohort (the HUNT Study).

BACKGROUND: Obesity has tripled worldwide since 1975 as environments are becoming more obesogenic. Our study investigates how changes in population weight and obesity over time are associated with genetic predisposition in the context of an obesogenic environment over 6 decades and examines the robustness of the findings using sibling design. METHODS AND FINDINGS: A total of 67,110 individuals aged 13-80 years in the Nord-Trøndelag region of Norway participated with repeated standardized body mass index (BMI) measurements from 1966 to 2019 and were genotyped in a longitudinal population-based health study, the Trøndelag Health Study (the HUNT Study). Genotyping required survival to and participation in the HUNT Study in the 1990s or 2000s. Linear mixed models with observations nested within individuals were used to model the association between a genome-wide polygenic score (GPS) for BMI and BMI, while generalized estimating equations were used for obesity (BMI ≥ 30 kg/m2) and severe obesity (BMI ≥ 35 kg/m2). The increase in the average BMI and prevalence of obesity was steeper among the genetically predisposed. Among 35-year-old men, the prevalence of obesity for the least predisposed tenth increased from 0.9% (95% confidence interval [CI] 0.6% to 1.2%) to 6.5% (95% CI 5.0% to 8.0%), while the most predisposed tenth increased from 14.2% (95% CI 12.6% to 15.7%) to 39.6% (95% CI 36.1% to 43.0%). Equivalently for women of the same age, the prevalence of obesity for the least predisposed tenth increased from 1.1% (95% CI 0.7% to1.5%) to 7.6% (95% CI 6.0% to 9.2%), while the most predisposed tenth increased from 15.4% (95% CI 13.7% to 17.2%) to 42.0% (95% CI 38.7% to 45.4%). Thus, for 35-year-old men and women, respectively, the absolute change in the prevalence of obesity from 1966 to 2019 was 19.8 percentage points (95% CI 16.2 to 23.5, p < 0.0001) and 20.0 percentage points (95% CI 16.4 to 23.7, p < 0.0001) greater for the most predisposed tenth compared with the least predisposed tenth, defined using the GPS for BMI. The corresponding absolute changes in the prevalence of severe obesity for men and women, respectively, were 8.5 percentage points (95% CI 6.3 to 10.7, p < 0.0001) and 12.6 percentage points (95% CI 9.6 to 15.6, p < 0.0001) greater for the most predisposed tenth. The greater increase in BMI in genetically predisposed individuals over time was apparent after adjustment for family-level confounding using a sibling design. Key limitations include a slightly lower survival to date of genetic testing for the older cohorts and that we apply a contemporary genetic score to past time periods. Future research should validate our findings using a polygenic risk score constructed from historical data. CONCLUSIONS: In the context of increasingly obesogenic changes in our environment over 6 decades, our findings reveal a growing inequality in the risk for obesity and severe obesity across GPS tenths. Our results suggest that while obesity is a partially heritable trait, it is still modifiable by environmental factors. While it may be possible to identify those most susceptible to environmental change, who thus have the most to gain from preventive measures, efforts to reverse the obesogenic environment will benefit the whole population and help resolve the obesity epidemic.

Supplementary drug treatment to reduce weight in adolescents with severe obesity. / Medikamentell tilleggsbehandling for vektreduksjon hos ungdom med alvorlig fedme.

In 2021, the Norwegian Medicines Agency approved the use of daily injection of liraglutide 3.0 mg (Saxenda) as a supplement to lifestyle treatment for weight control in children ≥ 12 years of age with obesity (isoBMI ≥ 30). We share the treatment experiences of six multidisciplinary obesity clinics in the specialist health service.

Perceptions of height and weight screening and associations with body image: a cross-sectional study in early primary school children.

BACKGROUND: Despite parental concern, few studies have investigated children's experiences with school-based screening of growth deviations. This study aimed to explore perceptions of height and weight screening and associations with body size dissatisfaction (BSD) among third-grade children aged 8-9 years in central Norway. METHODS: In a cross-sectional study between November 2021 and April 2022, perceptions of height and weight screening and BSD were assessed individually among 209 children (49% girls) through researcher-assisted interviews. RESULTS: Most children indicated satisfaction with the screening by selecting a happy emoji, whereas only 1% indicated dissatisfaction, by selecting an unhappy emoji. However, 23%-30% selected a neutral emoji, indicating either neutrality or a response between satisfaction and dissatisfaction. No difference in the perception of height and weight screening was found between genders or body mass index (BMI). Children with parents from non-Western countries had a higher risk of being less satisfied with the height screening (OR=3.0, 95% CI 1.2 to 7.3) than those from Western origin, and children attending schools with lower socioeconomic status (SES) had increased risk of being less satisfied with both height (OR=5.5, 95% CI 2.2 to 13.5) and weight screening (OR=4.0, 95% CI 1.7 to 9.3), compared with children from schools with medium-high SES. Twenty-three percent reported BSD, in which 14% and 9% desired a thinner or larger body, respectively, independent of gender and BMI. No association was found between BSD and the perception of weighing (OR=1.1, 95% CI 0.6 to 2.4), however, BSD was associated with being more satisfied with height screening (OR=0.3, 95% CI 0.1 to 0.8). CONCLUSION: In the present sample, most children indicated satisfaction with school-based height and weight screening, with no differences between gender or BMI category. However, more children of non-Western origin and from areas with low SES reported less satisfaction with the screening, independent of BSD.

Allergy-related diseases and early gut fungal and bacterial microbiota abundances in children.

BACKGROUND: The early gut microbiota has been proposed as an important link between environmental exposures and development of allergy-related diseases. Beyond the widely investigated associations between the gut bacterial microbiota, we investigated the involvement of early gut mycobiota and gut permeability in the pathogenesis of asthma, allergic rhinoconjunctivitis (AR) and eczema. METHODS: In the Probiotics in the Prevention of Allergy among Children in Trondheim trial with maternal probiotic supplementation, we collected faecal samples at four timepoints between 0 and 2 years from a cohort of 278 children. Clinical information on allergy-related diseases was collected in a paediatric examination at 2 years and questionnaires at 6 weeks and 1, 2 and 6 years. By quantitative PCR and 16S/ITS1 MiSeq rRNA gene sequencing, we analysed the gut bacterial and fungal microbiota abundance and bacterial diversity and explored associations with allergy-related diseases. We also measured gut permeability markers (lipopolysaccharide-binding protein [LBP] and fatty acid-binding protein 2 [FABP2]). RESULTS: Children with higher fungal abundance at 2 years were more likely to develop asthma and AR by 6 years, odds ratios 1.70 (95% CI: 1.06-2.75) and 1.41 (1.03-1.93), respectively. We explored causal connections, and children with eczema at 1-2 years appeared to have more mature bacterial microbiota, as well as being depleted of Enterococcus genus. Although LBP and FABP2 did not correlate with eczema, increased bacterial abundance was associated with increased serum FABP2. CONCLUSIONS: We observed positive associations between gut fungal abundance and allergy-related disease, but increased gut permeability does not appear to be involved in the underlying mechanisms for this association. Our findings should be confirmed in future microbiota studies.

Early Gut Fungal and Bacterial Microbiota and Childhood Growth.

Introduction: Childhood growth is a sensitive marker of health. Animal studies show increased height and weight velocity in the presence of fungal as well as antibiotic supplement in feed. Human studies on early gut microbiota and anthropometrics have mainly focused on bacteria only and overweight, with diverging results. We thus aimed to investigate the associations between childhood growth [height and body mass index (BMI)] and early fungal and bacterial gut microbiota. Methods: In a population-based cohort, a subset of 278 pregnant mothers was randomized to drink milk with or without probiotic bacteria during and after pregnancy. We obtained fecal samples in offspring at four time points between 0 and 2 years and anthropometric measurements 0 and 9 years. By quantitative PCR and 16S/ITS rRNA gene sequencing, children's gut microbiota abundance and diversity were analyzed against height standard deviation score (SDS) and BMI-SDS and presented as effect estimate (ß) of linear mixed models. Results: From 278 included children (149 girls), 1,015 fecal samples were collected. Maternal probiotic administration did not affect childhood growth, and the groups were pooled. Fungal abundance at 2 years was positively associated with height-SDS at 2-9 years (ß = 0.11 height-SDS; 95% CI, 0.00, 0.22) but not with BMI-SDS. Also, higher fungal abundance at 1 year was associated with a lower BMI-SDS at 0-1 year (ß = -0.09 BMI-SDS; 95% CI, -0.18, -0.00), and both bacterial abundance and bacterial alpha diversity at 1 year were associated with lower BMI-SDS at 0-1 year (ß = -0.13 BMI-SDS; 95% CI, -0.22, -0.04; and ß = -0.19 BMI-SDS; 95% CI, -0.39, -0.00, respectively). Conclusions: In this prospective cohort following 0-9-year-old children, we observed that higher gut fungal abundances at 2 years were associated with taller children between 2 and 9 years. Also, higher gut fungal and bacterial abundances and higher gut bacterial diversity at 1 year were associated with lower BMI in the first year of life. The results may indicate interactions between early gut fungal microbiota and the human growth-regulating physiology, previously not reported. Clinical Trial Registration: Clinicaltrials.gov, NCT00159523.

Quantifying the impact of genes on body mass index during the obesity epidemic: longitudinal findings from the HUNT Study.

OBJECTIVES: To study the trajectories of body mass index (BMI) in Norway over five decades and to assess the differential influence of the obesogenic environment on BMI according to genetic predisposition. DESIGN: Longitudinal study. SETTING: General population of Nord-Trøndelag County, Norway. PARTICIPANTS: 118 959 people aged 13-80 years who participated in a longitudinal population based health study (Nord-Trøndelag Health Study, HUNT), of whom 67 305 were included in analyses of association between genetic predisposition and BMI. MAIN OUTCOME MEASURE: BMI. RESULTS: Obesity increased in Norway starting between the mid-1980s and mid-1990s and, compared with older birth cohorts, those born after 1970 had a substantially higher BMI already in young adulthood. BMI differed substantially between the highest and lowest fifths of genetic susceptibility for all ages at each decade, and the difference increased gradually from the 1960s to the 2000s. For 35 year old men, the most genetically predisposed had 1.20 kg/m2 (95% confidence interval 1.03 to 1.37 kg/m2) higher BMI than those who were least genetically predisposed in the 1960s compared with 2.09 kg/m2 (1.90 to 2.27 kg/m2) in the 2000s. For women of the same age, the corresponding differences in BMI were 1.77 kg/m2 (1.56 to 1.97 kg/m2) and 2.58 kg/m2 (2.36 to 2.80 kg/m2). CONCLUSIONS: This study provides evidence that genetically predisposed people are at greater risk for higher BMI and that genetic predisposition interacts with the obesogenic environment resulting in higher BMI, as observed between the mid-1980s and mid-2000s. Regardless, BMI has increased for both genetically predisposed and non-predisposed people, implying that the environment remains the main contributor.

Health-related quality of life after camp-based family obesity treatment: an RCT.

OBJECTIVE: To compare the effects of a 2-year camp-based immersion family treatment for obesity with an outpatient family-based treatment for obesity on health-related quality of life (HRQoL) in two generations. DESIGN: Randomised controlled trial. SETTING: Rehabilitation clinic, tertiary care hospital and primary care. PATIENTS: Families with at least one child (7-12 years) and one parent, both with obesity. INTERVENTIONS: Summer camp for 2 weeks, with four repetition weekends, or lifestyle school, including four outpatient days over 4 weeks. Behavioural techniques to promote a healthier lifestyle. MAIN OUTCOME MEASURES: Children's and parents' HRQoL were assessed using generic and obesity-specific measures. Outcomes were analysed using linear mixed models according to intention to treat, and multiple imputations were used for missing data. RESULTS: Ninety children (50% girls) with a mean (SD) age of 9.7 (1.2) years and body mass index 28.7 (3.9) kg/m2 were included in the analyses. Summer camp children had an estimated mean (95% CI) of 5.3 (0.4 to 10.1) points greater improvement in adiposity-specific HRQoL score at 2 years compared with the lifestyle school children, and this improvement was even larger in the parent proxy-report, where mean difference was 7.3 (95% CI 2.3 to 12.2). Corresponding effect sizes were 0.33 and 0.44. Generic HRQoL questionnaires revealed no significant differences between treatment groups in either children or parents from baseline to 2 years. CONCLUSIONS: A 2-year family camp-based immersion obesity treatment programme had significantly larger effects on obesity-specific HRQoL in children's self-report and parent proxy-reports in children with obesity compared with an outpatient family-based treatment programme. TRIAL REGISTRATION NUMBER: NCT01110096.

Early gut mycobiota and mother-offspring transfer.

BACKGROUND: The fungi in the gastrointestinal tract, the gut mycobiota, are now recognised as a significant part of the gut microbiota, and they may be important to human health. In contrast to the adult gut mycobiota, the establishment of the early gut mycobiota has never been described, and there is little knowledge about the fungal transfer from mother to offspring. METHODS: In a prospective cohort, we followed 298 pairs of healthy mothers and offspring from 36 weeks of gestation until 2 years of age (1516 samples) and explored the gut mycobiota in maternal and offspring samples. Half of the pregnant mothers were randomised into drinking probiotic milk during and after pregnancy. The probiotic bacteria included Lactobacillus rhamnosus GG (LGG), Bifidobacterium animalis subsp. lactis Bb-12 and Lactobacillus acidophilus La-5. We quantified the fungal abundance of all the samples using qPCR of the fungal internal transcribed spacer (ITS)1 segment, and we sequenced the 18S rRNA gene ITS1 region of 90 high-quantity samples using the MiSeq platform (Illumina). RESULTS: The gut mycobiota was detected in most of the mothers and the majority of the offspring. The offspring showed increased odds of having detectable faecal fungal DNA if the mother had detectable fungal DNA as well (OR = 1.54, p = 0.04). The fungal alpha diversity in the offspring gut increased from its lowest at 10 days after birth, which was the earliest sampling point. The fungal diversity and fungal species showed a succession towards the maternal mycobiota as the child aged, with Debaryomyces hansenii being the most abundant species during breast-feeding and Saccharomyces cerevisiae as the most abundant after weaning. Probiotic consumption increased the gut mycobiota abundance in pregnant mothers (p = 0.01). CONCLUSION: This study provides the first insight into the early fungal establishment and the succession of fungal species in the gut mycobiota. The results support the idea that the fungal host phenotype is transferred from mother to offspring. TRIAL REGISTRATION: Clinicaltrials.gov NCT00159523.

Camp-based family treatment of childhood obesity: randomised controlled trial.

OBJECTIVE: To compare the effectiveness of a 2-year camp-based family treatment programme and an outpatient programme on obesity in two generations. DESIGN: Pragmatic randomised controlled trial. SETTING: Rehabilitation clinic, tertiary care hospital and primary care. PATIENTS: Families with at least one child (7-12 years) and one parent with obesity. INTERVENTIONS: Summer camp for 2 weeks and 4 repetition weekends or lifestyle school including 4 days family education. Behavioural techniques motivating participants to healthier lifestyle. MAIN OUTCOME MEASURES: Children: 2-year changes in body mass index (BMI) SD score (SDS). Parents: 2-year change in BMI. Main analyses: linear mixed models. RESULTS: Ninety children (50% girls) were included. Baseline mean (SD) age was 9.7 (1.2) years, BMI 28.7 (3.9) kg/m2 and BMI SDS 3.46 (0.75). The summer-camp children had a lower adjusted estimated mean (95% CI) increase in BMI (-0.8 (-3.5 to -0.2) kg/m2), but the BMI SDS reductions did not differ significantly (-0.11 (-0.49 to 0.05)). The 2-year baseline adjusted BMI and BMI SDS did not differ significantly between summer-camp and lifestyle-school completers, BMI 29.8 (29.1 to 30.6) vs 30.7 (29.8 to 31.6) kg/m2 and BMI SDS 2.96 (2.85 to 3.08) vs 3.11 (2.97 to 3.24), respectively. The summer-camp parents had a small reduction in BMI (-0.9 (-1.8 to -0.03) vs -0.8 (-2.1 to 0.4) in the lifestyle-school group), but the within-group changes did not differ significantly (0.3 (-1.7 to 2.2)). CONCLUSIONS: A 2-year family camp-based obesity treatment programme had no significant effect on BMI SDS in children with severe obesity compared with an outpatient family-based treatment programme. TRIAL REGISTRATION NUMBER: NCT01110096.