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Objectives: The timing and magnitude of adolescent growth may be influenced by ethnicity and early life factors. We aimed to (a) characterize ethnic differences in the magnitude, timing, and intensity of adolescent growth in height, weight, and BMI; (b) assess the effect of early childhood growth on adolescent growth in black children., Methods: Data were from the Birth to Twenty Plus cohort (Bt20+) in Johannesburg, South Africa (n = 3273). Height, weight, and BMI were modeled with ethnic comparisons using the SuperImposition by Translation and Rotation for 2089 participants who had data from 7 to 23 years. Relative weight gain and relative linear growth between 0 and 24 months and 24 and 60 months were generated. Multiple regression analyses were used to assess associations between childhood and adolescent growth., Results: White children were 5 cm (SE: 0.7) taller than black children through adolescence. Black boys had a later timing of adolescent height (0.65 years ±0.12) than white boys, which in black girls was 0.24 years (0.11) earlier than in white girls. Black girls had faster BMI velocity than white girls. Among black children, birth weight and both relative weight gain 0 to 24 and relative linear growth between 3 and 24 months and 24 and 60 months were positively associated with the magnitude of adolescent growth and negatively associated with timing., Conclusion: Sex dimorphism in ethnic differences in timing of adolescent height growth may reflect some yet unexplained drivers for rapid weight gain and obesity in black females but not black males. Rapid weight gain in early life may contribute to faster adiposity accrual in adolescence., (© 2020 Wiley Periodicals LLC.)

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Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)

Purpose: To assess the association between dietary intake patterns from 1 to 4 years and BMI and body shape at age of 6 years., Methods: This longitudinal study was based on 3374 Brazilian children from the 2004 Pelotas Birth Cohort Study. We used previously described dietary patterns from 1 to 4 years as the main exposure. We defined body shape using scores for corpulence (a recently described body shape component measured by Photonic Scanner), and trunk and gynoid fat mass percentage from DXA. We run linear regression models to evaluate the associations between dietary patterns from 1 to 4 years and BMI and body shape at 6 years., Results: Several apparent associations between dietary patterns and BMI or body shape were explained by sociodemographic factors. High adherence to snacks (positive loadings to coffee, bread and cookies) at 4 years predicted lower BMI, but higher gynoid fat mass percentage at 6 years, while higher adherence to staple at 2 years (positive loadings to rice and beans) predicted higher trunk fat mass and lower gynoid fat mass. Finally, higher scores on milks at 1 year (positive loading to breast milk) predicted higher gynoid fat mass at 6 years., Conclusion: There were inconsistent associations between dietary patterns in infancy and early childhood and BMI and body shape at 6 years. In adjusted analyses, higher adherence to breast milk at 1 year and to snacks at 4 years appeared to be beneficial for body shape, associated with lower BMI, but higher peripheral fat.

Background: Presumed benefits of human milk (HM) in avoiding rapid infancy weight gain and later obesity could relate to its nutrient composition. However, data on breast milk composition and its relation with growth are sparse., Objective: We investigated whether short-chain fatty acids (SCFAs), known to be present in HM and linked to energy metabolism, are associated with infancy anthropometrics., Methods: In a prospective birth cohort, HM hindmilk samples were collected from 619 lactating mothers at 4-8 wk postnatally [median (IQR) age: 33.9 (31.3-36.5) y, body mass index (BMI) (kg/m2): 22.8 (20.9-25.2)]. Their offspring, born at 40.1 (39.1-41.0) wk gestation with weight 3.56 (3.22-3.87) kg and 51% male, were assessed with measurement of weight, length, and skinfold thickness at ages 3, 12, and 24 mo, and transformed to age- and sex-adjusted z scores. HM SCFAs were measured by 1H-nuclear magnetic resonance spectroscopy (NMR) and GC-MS. Multivariable linear regression models were conducted to analyze the relations between NMR HM SCFAs and infancy growth parameters with adjustment for potential confounders., Results: NMR peaks for HM butyrate, acetate, and formic acid, but not propionate, were detected. Butyrate peaks were 17.8% higher in HM from exclusively breastfeeding mothers than mixed-feeding mothers (P = 0.003). HM butyrate peak values were negatively associated with changes in infant weight (standardized B  = -0.10, P = 0.019) and BMI (B = -0.10, P = 0.018) between 3 and 12 mo, and negatively associated with BMI (B = -0.10, P = 0.018) and mean skinfold thickness (B = -0.10, P = 0.049) at age 12 mo. HM formic acid peak values showed a consistent negative association with infant BMI at all time points (B < = -0.10, P < = 0.014), whereas HM acetate was negatively associated with skinfold thickness at 3 mo (B = -0.10, P = 0.028) and 24 mo (B = -0.10, P = 0.036)., Conclusions: These results suggest that HM SCFAs play a beneficial role in weight gain and adiposity during infancy. Further knowledge of HM SCFA function may inform future strategies to support healthy growth., (Copyright © American Society for Nutrition 2019.)

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.

Background: In populations of European ancestry, the genetic contribution to body mass index (BMI) increases with age during childhood but then declines during adulthood, possibly due to the cumulative effects of environmental factors. How the effects of genetic factors on BMI change with age in other populations is unknown., Subjects and Methods: In a rural Gambian population (N=2535), we used a combined allele risk score, comprising genotypes at 28 'Caucasian adult BMI-associated' single nucleotide polymorphisms (SNPs), as a marker of the genetic influence on body composition, and related this to internally-standardised z-scores for birthweight (zBW), weight-for-height (zWT-HT), weight-for-age (zWT), height-for-age (zHT), and zBMI cross-sectionally and longitudinally., Results: Cross-sectionally, the genetic score was positively associated with adult zWT (0.018±0.009 per allele, p=0.034, N=1426) and zWT-HT (0.025±0.009, p=0.006), but not with size at birth or childhood zWT-HT (0.008±0.005, p=0.11, N=2211). The effect of the genetic score on zWT-HT strengthened linearly with age from birth through to late adulthood (age interaction term: 0.0083 z-scores/allele/year; 95% CI 0.0048 to 0.0118, p=0.0000032)., Conclusions: Genetic variants for obesity in populations of European ancestry have direct relevance to bodyweight in nutritionally deprived African settings. In such settings, genetic obesity susceptibility appears to regulate change in weight status throughout the life course, which provides insight into its potential physiological role., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Background: Childhood growth affects long-term health and could contribute to health inequalities that persist throughout life., Methods: We compared growth data of 4-year-old to 6-year-old children born 1997-2002 in UK (n=15,168), Sweden (n=6749) and rural China (n=10,327). SD scores (SDS) were calculated against the WHO Growth Standard. Obesity and overweight were defined by the International Obesity Taskforce cut-offs, and stunting, underweight and thinness by height, weight or body mass index (BMI)<-2 SDS. Associations with maternal education were standardised by calculating the Slope Index of Inequality (SII)., Results: Mean SDS height, weight and BMI in the UK (-0.01, 0.42, 0.62, respectively) and Sweden (0.45, 0.59, 0.45) were higher than in China (-0.98, -0.82, -0.29). Higher maternal education was consistently associated with taller offspring height SDS (SII: UK 0.25; Sweden 0.17; China 1.06). Underweight and stunting were less common in the UK (prevalence: 0.6% and 2.2%, respectively) and Sweden (0.3% and 0.6%) than in China (9.5% and 16.4%), where these outcomes were inversely associated with maternal education (SII: -25.8% and -12.7%). Obesity prevalence in the UK, Sweden and China was 4.8%, 3.7% and 0.4%, respectively. Maternal education was inversely associated with offspring obesity in the UK (SII: -3.3%) and Sweden (-2.8%), but not in China (+0.3%)., Conclusions: Higher maternal education was associated with more favourable growth in young children: lower obesity and overweight in the UK and Sweden, and lower stunting and underweight in rural China. Public health strategies to optimise growth in early childhood need to acknowledge socioeconomic factors, but possibly with a different emphasis in different settings.

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.

Background: High birth weight is associated with adult body mass index (BMI). We hypothesized that birth weight and BMI may partly share a common genetic background., Objective: The objective was to examine the associations of 12 established BMI variants in or near the NEGR1, SEC16B, TMEM18, ETV5, GNPDA2, BDNF, MTCH2, BCDIN3D, SH2B1, FTO, MC4R, and KCTD15 genes and their additive score with birth weight., Design: A meta-analysis was conducted with the use of 1) the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk, Hertfordshire, Fenland, and European Youth Heart Study cohorts (n(max) = 14,060); 2) data extracted from the Early Growth Genetics Consortium meta-analysis of 6 genome-wide association studies for birth weight (n(max) = 10,623); and 3) all published data (n(max) = 14,837)., Results: Only the MTCH2 and FTO loci showed a nominally significant association with birth weight. The BMI-increasing allele of the MTCH2 variant (rs10838738) was associated with a lower birth weight (β ± SE: -13 ± 5 g/allele; P = 0.012; n = 23,680), and the BMI-increasing allele of the FTO variant (rs1121980) was associated with a higher birth weight (β ± SE: 11 ± 4 g/allele; P = 0.013; n = 28,219). These results were not significant after correction for multiple testing., Conclusions: Obesity-susceptibility loci have a small or no effect on weight at birth. Some evidence of an association was found for the MTCH2 and FTO loci, ie, lower and higher birth weight, respectively. These findings may provide new insights into the underlying mechanisms by which these loci confer an increased risk of obesity.

Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10⁻⁸), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

Objectives: The objective of this study was to explore the influence of maternal prenatal characteristics and behaviors and of weight and BMI gain during early childhood on the timing of various puberty outcomes in girls who were enrolled in the Avon Longitudinal Study of Parents and Children., Methods: Repeated self-assessments of pubertal development were obtained from approximately 4000 girls between the ages of 8 and 14. Data on prenatal characteristics and weight at birth and 2, 9, and 20 months of age were obtained from questionnaires, birth records, and clinic visits. Infants' weights were converted to weight-for-age and BMI SD scores (SDSs; z scores), and change values were obtained for the 0- to 20-month and other intervals within that age range. We used parametric survival models to estimate associations with age of entry into Tanner stages of breast and pubic hair and menarche., Results: Maternal initiation of menarche at age<12, smoking during pregnancy, and primiparity were associated with earlier puberty. A 1-unit increase in the weight SDS change values for the 0- to 20-month age interval was associated with earlier ages of entry into pubertal outcomes (0.19-0.31 years). Increases in the BMI SDS change values were also associated with earlier entry into pubertal outcomes (0.07-0.11 years)., Conclusions: Many of the maternal prenatal characteristics and weight and BMI gain during infancy seemed to have similar influences across different puberty outcomes. Either such early factors have comparable influences on each of the hormonal processes involved in puberty, or processes are linked and awakening of 1 aspect triggers the others.

Background: Several studies reported inverse associations between birth weight and central adiposity in adults. However, few studies investigated the contributions of different abdominal fat compartments., Objective: We examined associations between birth weight and adult visceral and subcutaneous abdominal fat in the population-based Fenland study., Design: A total of 1092 adults (437 men and 655 women) aged 30-55 y had available data on reported birth weight, standard anthropometric measures, and visceral and subcutaneous abdominal fat estimated by ultrasound. In a subgroup (n = 766), dual-energy X-ray absorptiometry assessment of total abdominal fat was performed. Linear regression models were used to analyze relations between birth weight and the various fat variables adjusted for sex, age, education, smoking, and body mass index (BMI)., Results: After adjustment for adult BMI, there was an inverse association between birth weight and total abdominal fat [B (partial regression coefficient expressed as SD/1-kg change in birth weight) = -0.09, P = 0.002] and visceral fat (B = -0.07, P = 0.01) but not between birth weight and subcutaneous abdominal fat (B = -0.01, P = 0.3). Tests for interaction showed that adult BMI modified the association between birth weight and visceral fat (P for interaction = 0.01). In stratified analysis, the association between birth weight and visceral fat was apparent only in individuals with the highest BMI tertile (B = -0.08, P = 0.04)., Conclusions: The inverse association between birth weight and adult abdominal fat appeared to be specific to visceral fat. However, associations with birth weight were apparent only after adjustment for adult BMI. Therefore, we suggest that rapid postnatal weight gain, rather than birth weight alone, leads to increased visceral fat.

Background: Large-scale genome-wide association studies have identified 12 genetic loci that are robustly associated with body mass index (BMI)., Objectives: We examined associations and compared effect sizes of these newly identified obesity susceptibility loci with various anthropometric traits and assessed their cumulative effects and predictive value for obesity risk., Design: We genotyped 12 single nucleotide polymorphisms (SNPs) from each locus in 20,431 individuals (age: 39-79 y) from the population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort. General linear model and logistic regression were used to examine associations, and the area under the receiver operating characteristic curve (AUC) was used to assess the predictive value of these variants for obesity risk., Results: Effect sizes of the risk alleles ranged between 0.058 and 0.329 for BMI (in kg/m(2)), between 0.094 and 0.866 kg for weight, and between 0.085 and 0.819 cm for waist circumference, with rs1121980 (FTO locus) showing the largest effect. Risk alleles of rs7132908 (FAIM2 locus) and rs17782313 (MC4R locus) were also associated with taller height. On average, each additional risk allele was associated with increases of 0.149 in BMI (P = 1.54 x 10(-22)), 0.444 kg in body weight (P = 9.88 x 10(-22)), and 0.357 cm in waist circumference (P = 1.10 x 10(-18)) and 10.8% (P = 9.83 x 10(-16)) and 5.5% (P = 3.38 x 10(-10)) increased risks of obesity and overweight, respectively. All SNPs combined explained 0.9% of BMI variation, with an AUC of 0.574 (95% CI: 0.559, 0.590) for prediction of obesity., Conclusions: Common variants for BMI have small effects on obesity measures and show different association patterns with anthropometric traits, with the largest effect shown for the FTO locus. These variants have cumulative effects, yet their predictive value for obesity risk is limited.

Background/aims: The common polymorphism rs17782313 lying 188 kb downstream of the MC4R gene has recently been found to be unequivocally associated with body mass index (BMI) and obesity risk in adults and children. Our objective was to test the association between rs17782313 and neonatal weight gain in a contemporary population., Methods: This was a cross-sectional, hospital-based study using 278 healthy Caucasian newborns [142 girls; gestational age (mean +/- SD) 39.3 +/- 1.4 weeks, birth weight 3.1 +/- 0.6 kg]. Body composition was assessed by dual-energy X-ray absorptiometry (DXA) at approximately 13 days (range 9-20) and rs17782313 was genotyped by restriction fragment length polymorphism analysis., Results: rs17782313 was not associated with weight, length or ponderal index at birth. However, it was associated with changes in BMI (p = 0.0004) over the first 2 weeks of life and with body weight (p = 0.02) and BMI (p = 0.007) at age 2 weeks. Despite this, DXA measures of fat and lean mass failed to show any simple associations., Conclusion: Similar to other genetic variants associated with childhood and adult obesity, the association between rs17782313 genotype and body weight develops rapidly during the first 2 weeks of life, once caloric intake is regulated by the infant's appetite., (Copyright (c) 2010 S. Karger AG, Basel.)

Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.

Objective: We investigated the effects of normal variations in maternal glycemia on birth size and other birth outcomes., Research Design and Methods: Women in two unselected birth cohorts, one retrospective (n = 3,158) and one prospective (n = 668), underwent an oral glucose challenge at 28 weeks of gestation. In the retrospective study, glycemia was linked to routine birth records. In the prospective study, offspring adiposity was assessed by skinfold thickness from birth to age 24 months., Results: In the retrospective study, within the nondiabetic range (2.1-7.8 mmol/l), each 1 mmol/l rise in the mother's 60-min glucose level was associated with a (mean +/- SEM) 2.1 +/- 0.8% (P = 0.006) rise in absolute risk of assisted vaginal delivery, a 3.4 +/- 0.8% (P < 0.0001) rise in emergency cesarean delivery, a 3.1 +/- 0.7% (P < 0.0001) rise in elective cesarean delivery, and a 46 +/- 8 g (P < 0.0001) increase in offspring birth weight. In the prospective study, fetal macrosomia (birth weight >90th centile) was independently related to the mother's fasting glucose (odds ratio 2.61 per +1 mmol/l [95% CI 1.15-5.93]) and prepregnancy BMI (1.10 per +1 kg/m(2) [1.04-1.18]). The mother's higher fasting glycemia (P = 0.004), lower insulin sensitivity (P = 0.01), and lower insulin secretion (P = 0.02) were independently related to greater offspring adiposity at birth. During postnatal follow-up, the correlation between the mother's glycemia and offspring adiposity disappeared by 3 months, whereas prepregnancy BMI was associated with offspring adiposity that was only apparent at 12 and 24 months (both P < 0.05)., Conclusions: Prepregnancy BMI, pregnancy glycemia, insulin sensitivity, and insulin secretion all contribute to offspring adiposity and macrosomia and may be separate targets for intervention to optimize birth outcomes and later offspring health.

Context: The IGF2 gene (IGF2) plays a key role in growth and is a candidate for association with obesity. Previous studies have reported that polymorphisms in IGF2 are associated with body weight and body mass index (BMI), but the results have been inconsistent., Objectives: The aim of this study was primarily to confirm the association with BMI and, secondarily, to study the associations with other indices of body size., Methods: In a sample of 2797 women and 2203 men aged 39-79 participating in the Norfolk arm of the European Prospective Investigation of Cancer, we genotyped three single nucleotide polymorphisms (SNPs) in the IGF2 gene that were previously associated with BMI [6815 A/T, 1156 T/C (G/A), and 820 G/A (ApaI)]., Results: No significant associations were observed between these SNPs and BMI. However, all three SNPs were significantly associated with height (P = 0.03 to 0.001). In a backward elimination regression analysis, two SNPs, 1156 T/C (G/A) and 820 G/A, remained independently associated with height (P = 0.003 and P = 0.038, respectively). Haplotype analysis of these two SNPs showed that carriers of the GA haplotype were shorter than carriers of each of the other three haplotypes (P < 0.001 for all comparisons)., Conclusions: We did not confirm the previously reported associations between IGF2 polymorphisms and BMI. However, our results suggest that common variation in the IGF2 gene may be associated with adult height. IGF2 could be considered as a candidate gene for future research on mechanisms for the association between height and chronic diseases, such as cancer, diabetes, and coronary heart disease.

Context: Polymorphism at the insulin gene (INS) variable number of tandem repeat (VNTR) shows variable associations with childhood body mass index (BMI) in different populations., Objective: The objective of this study was to observe INS VNTR associations with body composition and insulin secretion in children., Design: The study was designed as a prospective birth cohort study., Participants: A total of 947 children genotyped for the INS VNTR participated., Main Outcome Measures: Main outcome measures were whole body dual x-ray emission absorptiometry at 9 yr to estimate height-corrected fat mass index (FMI), truncal FMI, and fat-free mass, and insulin secretion after oral glucose at 8 yr., Results: Homozygous III/III children had higher BMI (P = 0.020), FMI (P = 0.015), and truncal FMI (P = 0.022) at 9 yr than class I bearers, but no difference in fat-free mass (P = 0.23). Gain in weight sd score between birth and 3 yr was associated positively with BMI, FMI, and truncal FMI in class I bearers, but not in III/III children (p-interaction with genotype = 0.009-0.066). INS VNTR genotype was not associated overall with insulin secretion at 8 yr (P = 0.64), but class I bearers showed a stronger positive correlation between insulin secretion and BMI at 8 yr (regression coefficient +/- se, 0.26 +/- 0.05; P < 0.0001) than III/III children (-0.10 +/- 0.07; P = 0.48) (p-interaction = 0.003)., Conclusion: We clarified that the overall association between INS VNTR class III/III genotype and larger BMI in this population relates to fat mass, but not fat-free mass. In contrast, among the subgroup of children who showed rapid infancy weight gain, class I bearers tended to have larger BMI and fat mass than III/III children. This genetic interaction could relate to insulin secretion, which, in class I bearers, increased more rapidly with overweight and obesity.

Objective: Rapid infant weight gain has been shown to predict later obesity risk; however, it is unclear which factors influence infant diet and weight gain. The objective of this study was to determine whether different feeding patterns and energy intakes that are provided to infants affect body weight and BMI later in childhood., Methods: This representative birth cohort study was conducted in the United Kingdom. Energy intake at age 4 months was estimated from 1-day unweighed dietary records in 881 infants and related to their childhood weight gain and BMI., Results: Among formula- or mixed-fed infants (N = 582), energy intake was higher in first-born infants (mean +/- SE: 2730 +/- 29.4 kJ/day; n = 263) than in subsequent-born infants (2620.8 +/- 25.2 kJ/day; n = 296). Energy intake at 4 months was also higher in infants who were given solid foods earlier (1-2 months: 2805.6 +/- 50.4 kJ/day, n = 89; 2-3 months: 2658.6 +/- 25.2 kJ/day, n = 339; 4+ months: 2587.2 +/- 46.2 kJ/day, n = 111). Higher energy intake at 4 months predicted greater weight gain between birth to age 1, 2, or 3 years and larger body weight and BMI at ages 1 to 5 years. No significant associations were seen in breastfed infants (N = 299)., Conclusions: Among formula- or mixed-fed infants, dietary energy intake at age 4 months predicted postnatal weight gain and childhood obesity risk. Both prenatal and postnatal factors may influence infant energy intake and postnatal weight gain.