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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.

ABSTRACT: 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.

SUBMITTER: Brandkvist M

PROVIDER: S-EPMC7906755 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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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.

Brandkvist Maria M Bjørngaard Johan Håkon JH Ødegård Rønnaug Astri RA Åsvold Bjørn Olav BO Smith George Davey GD Brumpton Ben B Hveem Kristian K Richardson Tom G TG Vie Gunnhild Åberge GÅ

Human molecular genetics 20210201 24

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 re ...[more]

PMID: 33276378

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Project description:BackgroundChildhood socioeconomic position (SEP) has previously been associated with increased risk of overweight among children and adolescents. However, it remains uncertain whether the timing of exposure is important in relation to developing overweight in early adulthood. We aimed to examine how SEP during early (0-8 years) and late childhood (9-14 years) relates to overweight at age 15, 18 and 21.MethodsLongitudinal study in Western Denmark of 2879 young people (aged 15 in 2004). Exposure variables from registers were yearly household income, parental highest educational level and parental labour market participation (LMP), supplemented with questionnaire information about "family functioning" (age 15). Outcome variables were overweight and obesity, measured at three-time points.We analyzed the adjusted associations between childhood SEP and overweight and obesity using multinomial logistic regression, stratified on gender.ResultsEarly childhood: Parental lower educational level increased girls' risk of overweight and obesity at age 18 and 21 between RR = 1.8 (95% CI 1.0;3.4) and RR = 5.2 (95% CI 1.4;19.3). Girls reporting poor "family functioning" had up to twice the risk of overweight and obesity at age 21. Boys, whose fathers had a lower level of education had up to 2.4 times the risk of obesity at age 21. Parental low LMP increased boys' risk of obesity at age 18 and 21 between RR = 2.2 (95% CI 1.3;3.8) and RR = 2.8 (95% CI 1.3;6.1). Late childhood: Parental lower level of education tripled the risk of overweight and obesity among girls at age 18 and among both genders at age 21.ConclusionThis study confirmed to some extent that economic, social and psychological insecurity and inequality as measured by lower parental educational level, lower household income, low labour market participation and poor family function during childhood was associated with an increased risk of overweight and especially obesity in adolescence and early adulthood in both genders. Despite some imprecise measures, the direction of the associations pointed to several associations, which all were in the hypothesized direction. Timing of lower household income and parental low LMP in childhood seemed to be gender-specific in some way, but this warrants more studies.

Project description:BackgroundReports on body mass index (BMI) trajectories from childhood into late adolescence, their determinants, and subsequent cardiometabolic risk markers, particularly among European populations have been few. Moreover, sex-specific investigation is necessary considering the sex difference in BMI, and the sex-specific association between BMI and some cardiometabolic risk markers.MethodsUsing a sample from the DOrtmund Nutritional and Anthropometric Longitudinally Designed study, we explored sex-specific trajectories of the BMI standard deviation score (SDS) from 4 to 18 years of age in 354 males and 335 females by latent (class) growth models. The determinants of trajectory were assessed by logistic regression. We identified cardiometabolic risk markers that were highly associated with BMI SDS trajectory by random forest regression, and finally we used generalized linear models to investigate differences in the identified cardiometabolic risk markers between pairs of trajectories.ResultsWe observed four: 'low-normal weight', 'mid-normal weight', 'high-normal weight', and 'overweight', and three: ''low-normal weight', 'mid-normal weight', and 'high-normal weight' trajectories in males and females, respectively. Higher maternal prepregnancy BMI was associated with the 'overweight' trajectory, and with 'high-normal weight' trajectory in both sexes. In addition, employed mothers and first-born status were associated with 'high-normal weight' trajectory in females. BMI SDS trajectory was associated with high-density lipoprotein-cholesterol and interleukin-18 (IL-18) in males, and diastolic blood pressure and interleukin-6 (IL-6) in females. However, only males following the 'overweight' trajectory had significantly higher IL-18 when compared to their 'low-normal weight' counterpart.ConclusionsWe identified sex-specific distinct trajectories of BMI SDS from childhood into late adolescence, higher maternal prepregnancy BMI as a common determinant of the 'high-normal weight' and 'overweight' trajectories, and 'overweight' trajectory being associated with elevated IL-18 in late adolescence-young adulthood. This study emphasizes the role of maternal prepregnancy BMI in overweight, and highlights IL-18 as a cardiometabolic signature of overweight across life.

Project description:Importance:Cesarean birth has been associated with higher risk of obesity in offspring, but previous studies have focused primarily on childhood obesity and have been hampered by limited control for confounders. Objective:To investigate the association between cesarean birth and risk of obesity in offspring. Design, Setting, and Participants:A prospective cohort study was conducted from September 1, 1996, to December 31, 2012, among participants of the Growing Up Today Study, including 22?068 offspring born to 15?271 women, followed up via questionnaire from ages 9 to 14 through ages 20 to 28 years. Data analysis was conducted from October 10, 2015, to June 14, 2016. Exposure:Birth by cesarean delivery. Main Outcomes and Measures:Risk of obesity based on International Obesity Task Force or World Health Organization body mass index cutoffs, depending on age. Secondary outcomes included risks of obesity associated with changes in mode of delivery and differences in risk between siblings whose modes of birth were discordant. Results:Of the 22?068 offspring (20?950 white; 9359 male and 12?709 female), 4921 individuals (22.3%) were born by cesarean delivery. The cumulative risk of obesity through the end of follow-up was 13% among all participants. The adjusted risk ratio for obesity among offspring delivered via cesarean birth vs those delivered via vaginal birth was 1.15 (95% CI, 1.06-1.26; P?=?.002). This association was stronger among women without known indications for cesarean delivery (adjusted risk ratio, 1.30; 95% CI, 1.09-1.54; P?=?.004). Offspring delivered via vaginal birth among women who had undergone a previous cesarean delivery had a 31% (95% CI, 17%-47%) lower risk of obesity compared with those born to women with repeated cesarean deliveries. In within-family analysis, individuals born by cesarean delivery had 64% (8%-148%) higher odds of obesity than did their siblings born via vaginal delivery. Conclusions and Relevance:Cesarean birth was associated with offspring obesity after accounting for major confounding factors. Although additional research is needed to clarify the mechanisms underlying this association, clinicians and patients should weigh this risk when considering cesarean delivery in the absence of a clear indication.

Dataset Information

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.

Publications

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.

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