The findings are summarized in the published abstract of a study drawing on the China PEACE Million Persons Project between 2017 and 2023. Participants were considered at high cardiovascular risk if they had a history of cardiovascular disease, hypertension or dyslipidemia, or a 10-year CVD risk of at least 20%. Investigators used K-means clustering to identify BMI trajectories from baseline BMI and the annual rate of BMI change. Multivariable Cox models then assessed associations between those trajectories and the primary outcomes of all-cause and CVD hospitalization. During a median follow-up of 3.6 years, the study recorded 2,272 all-cause hospitalizations and 617 CVD hospitalizations.

Four trajectories were identified. The largest, comprising 50.9% of participants, was normal weight-stable. Rapid gainers accounted for 4.4% and had a normal baseline BMI with a median annual increase of 1.80 kg/m² per year. Obese-slow losers represented 39.5%, remaining obese with minimal weight reduction and a median annual change of −0.20 kg/m² per year. Obese-rapid losers made up 4.9%; this group had the highest baseline BMI and a median annual change of −2.20 kg/m² per year.

Compared with normal weight-stable participants, rapid gainers had an adjusted hazard ratio of 1.44 (95% confidence interval [CI] 1.10–1.88) for all-cause hospitalization, while obese-slow losers had an adjusted hazard ratio of 1.17 (95% CI 1.07–1.28). Obese-rapid losers also had higher all-cause hospitalization risk, with an adjusted hazard ratio of 1.39 (95% CI 1.09–1.78). For CVD hospitalization, the association was significant among rapid gainers, with an adjusted hazard ratio of 1.86 (95% CI 1.16–2.96), and obese-slow losers, with an adjusted hazard ratio of 1.26 (95% CI 1.06–1.50). The corresponding estimate for obese-rapid losers was 1.57 (95% CI 0.97–2.54), which the abstract described as borderline.

The results are observational associations and do not establish that BMI changes caused the hospitalization outcomes. The obese-rapid-loser group had higher socioeconomic status but also a greater burden of comorbidity, complicating interpretation of its elevated all-cause risk. The study’s scope was limited to adults at high CVD risk in Anhui, and the available source is the article abstract rather than a full assessment of the published paper. The authors concluded that rapid weight loss among people with obesity was not uniformly associated with favorable hospitalization outcomes and called for evaluation of the nature of weight loss, not only its magnitude.

Subject of Research: Associations between BMI change patterns and hospitalization risk among high-cardiovascular-risk adults in Anhui, China

Article Title: Body mass index change patterns and risk of hospitalization among populations at high cardiovascular risk: findings from the China PEACE Million Persons Project

Article References: Wang, Q., Wang, K., Liu, Z., Wu, G., Yuan, F., & Chen, K. (2026). Body mass index change patterns and risk of hospitalization among populations at high cardiovascular risk: findings from the China PEACE Million Persons Project. BMC Public Health. https://doi.org/10.1186/s12889-026-29855-z

Image Credits: AI Generated

DOI: 10.1186/s12889-026-29855-z

Keywords: body mass index, BMI trajectories, hospitalization risk, cardiovascular disease, high-risk adults, prospective cohort, weight change, China, Body, mass, index, change

The study’s scale is unprecedented for this age group. The team, led by researchers at the University of Cambridge and the University of Bergen, analysed age-standardised and sex-standardised BMI at eleven timepoints, from six weeks to eight years of age, in up to 62,276 children from the Norwegian Mother, Father and Child Cohort Study (MoBa). Across those timepoints they identified 369 genome-wide significant associations, which collapsed into 152 independent signals — a dramatic increase over the 25 loci found in the largest previous study of measured childhood BMI. Ninety-four percent of the 116 loci newly identified for BMI before age five had never been reported before, and none of the signals showed evidence of sex-specific effects.

A striking feature of the data is how much the genetic architecture of BMI changes with age. SNP-based heritability estimates rose after birth to a peak around the ‘adiposity peak’ at age one, then declined toward the ‘adiposity rebound’ around age five to six, mirroring the natural trajectory of body fat in early life. Genetic correlations told a similar story: the correlation between BMI in infancy and BMI in later childhood was only modest, at 0.39, and the correlation between childhood and adult BMI was lower still, at 0.19. In other words, the genetic variants that make a baby chubby are largely not the same ones that determine adult body size.

To push discovery further, the researchers used a statistical technique called genomic structural equation modelling to fuse three childhood-related traits into a single ‘childhood adiposity’ factor: BMI at age eight in MoBa, recalled comparative body size at age ten from 444,345 UK Biobank participants, and a genome-wide study of age at menarche, a trait tightly linked to early-life adiposity. This yielded an effective sample size of 599,924 individuals and 526 additional independent signals. A polygenic score built from the combined 624 signals explained up to 9.2 percent of variation in childhood BMI at age nine in the independent Avon Longitudinal Study of Parents and Children — outperforming scores based on adult BMI for every timepoint below age five.

When the team clustered the 624 signals by how their effects unfolded across childhood, two clear trajectories emerged. A ‘Transient’ group of 115 variants influenced BMI only during infancy, peaking between six weeks and about twelve months, while a ‘Persistent’ group of 507 variants continued to act into later childhood. The distinction matters clinically: in a disease-wide analysis of UK Biobank data, transient signals did not raise the risk of any adult disease and appeared mildly protective against type 2 diabetes and hypertension, whereas persistent signals raised cardiometabolic risk in ways that vanished once adult BMI was accounted for. The message is that infant fat that later resolves carries no long-term penalty — and may even confer benefit.

Gene-mapping analyses linked 434 high-confidence genes to the signals, and among them were eleven components of the leptin–melanocortin pathway, the master neuroendocrine circuit of appetite regulation whose disruption causes severe early-onset obesity. Signals tied to BSX, GNAS, LEPR and PCSK1 showed childhood-specific effects, while incretin pathway genes — GLP1R and GIPR, the very receptors targeted by today’s blockbuster weight-loss drugs — also emerged with effects confined largely to childhood. Notably, none of the GLP1R signals was associated with BMI beyond early childhood, and one PCSK1 variant even showed opposite effects on BMI in infancy and adulthood. Because the authors found that rare variants in these same pathways act more strongly in children than in adults, they suggest that drugs targeting the leptin–melanocortin pathway, such as leptin and setmelanotide, may be more effective in children than in adults.

Single-nucleus RNA sequencing data from the human hypothalamus added a neurobiological dimension. Childhood adiposity signals were enriched in 260 of 452 mapped hypothalamic cell populations, all of them neuronal — and nineteen of these were enriched only for childhood, not adult, signals. Five of the child-specific populations sit in the arcuate nucleus, the hypothalamic hub of energy homeostasis, and another five in the mammillary bodies, a region better known for memory. These cell populations were marked by expression of leptin–melanocortin and incretin components such as LEPR, POMC, MC4R, GLP1R and GIPR, hinting at brain circuits that regulate body fat specifically during development.

Whole-genome sequencing of 479,615 UK Biobank participants then extended the search to rare variants. Burden tests implicated six genes — ADCY3, CALCR, MC4R, MRAP2, POMC and MYH13 — with rare protein-coding variants that showed stronger associations with recalled childhood adiposity than with adult BMI. Four of the six encode central components of the leptin–melanocortin pathway, and the associations for ADCY3 and MRAP2 provided the first population-scale evidence that single copies of damaging variants in these severe-obesity genes measurably shift childhood body size. A novel association at MYH13, a muscle gene, affected childhood adiposity but showed no link to adult BMI at all.

The Norwegian cohort’s parent–child trios also allowed the team to probe genomic imprinting — the parent-of-origin silencing of certain genes. Evidence of imprinting emerged at signals near known imprinted regions, including a maternal effect at KLF14 on infancy BMI that reverses direction in adulthood, a childhood-specific paternal effect at GNAS, and a novel paternal-only association near ZDBF2, a gene that in mice regulates neonatal feeding and growth. The authors argue that these findings extend the classic parental-conflict hypothesis of imprinting, which was developed for fetal growth and puberty timing, to the regulation of childhood adiposity itself.

The study has limitations the authors acknowledge: the cohorts were of northern European ancestry, BMI in infancy is an imperfect proxy for fat mass, and the hypothalamic cell atlas was built from adult autopsy tissue. Larger, more diverse studies with directly measured infant body composition will be needed. Even so, the conclusion is hard to escape. With 624 signals — comparable to the 941 found for adult BMI in more than 700,000 people — childhood adiposity genetics proved at least as informative as its adult counterpart, and far more revealing about core energy-balance biology. As the authors put it, childhood appears to be a more sensitive window for detecting variation in the key endocrine and neuropeptide pathways that regulate how our bodies store fat, a finding that could reshape both obesity drug development and early-life prevention strategies.

Subject of Research: Genome-wide association and sequencing analysis of common and rare genetic variants influencing adiposity across childhood

Article Title: Genome-wide mapping of common and rare variant effects on adiposity across childhood

Article References: Kentistou, K. A., Sundfjord, J., Karimi, R., Kaisinger, L. R., Hofmeister, R. J., Fragoso-Bargas, N., Lupu, A. E., Zhao, Y., Tadross, J. A., Steuernagel, L., Dowsett, G. K. C., Lockhart, S., Brüning, J. C., Liu, J., Cortes, A., Lo, Y., Davitte, J., Clement, L., Havdahl, A., … Johansson, S. (2026). Genome-wide mapping of common and rare variant effects on adiposity across childhood. Nature Genetics. https://doi.org/10.1038/s41588-026-02772-y

Image Credits: AI Generated

DOI: 10.1038/s41588-026-02772-y

Keywords: childhood obesity, genome-wide association study, adiposity, leptin-melanocortin pathway, incretin signaling, hypothalamus, rare variants, genomic imprinting, polygenic scores, MoBa cohort, UK Biobank, BMI trajectories

The research drew on one of the world’s most remarkable longitudinal resources, the Copenhagen School Health Records Register. For decades, school physicians in Copenhagen measured the height and weight of virtually every schoolchild in the city, creating a meticulously preserved archive of childhood body size. The investigators harnessed this register to follow 66,906 females and 71,479 males born between 1952 and 1996, all of whom had weight and height measurements recorded between the ages of 6 and 15 years. By linking these childhood records to Danish national registers of hospital diagnoses and causes of death, the team could track which individuals later developed coronary heart disease, defined as diagnoses occurring at age 25 or beyond.

A central methodological strength of the study lies in how it characterized childhood growth. Rather than relying on a single measurement at one age, the researchers used latent class trajectory modelling, a statistical technique that identifies groups of individuals who share similar patterns of change over time. Five sex-specific childhood BMI trajectories emerged from the data, ranging from trajectories that remained within the lower average range to those tracking toward overweight and obesity. This approach captures the dynamics of growth, recognizing that a child whose BMI climbs steadily through the school years may carry a different cardiovascular risk profile than a child whose BMI stays stable, even if their measurements at any single age look similar.

During the follow-up period, 1,642 females and 3,456 males were diagnosed with coronary heart disease. The team then asked a question that had never been answered at this scale: does a parental history of cardiovascular disease modify the relationship between childhood BMI trajectories and early-onset heart disease? Family history is a well-established risk factor in its own right, and previous studies have shown that offspring of parents with cardiovascular disease face higher risks themselves. It was plausible that inherited or shared familial factors might amplify the harm of excess childhood adiposity, or alternatively that a strong family history might dominate risk to the point of overshadowing childhood body size.

The answer was a clear and somewhat surprising negative. Parental cardiovascular disease did not modify the associations between childhood BMI trajectory and later coronary heart disease. In other words, the increased risk conveyed by an overweight or obese childhood trajectory operated independently of whether a child’s parents had experienced heart disease. This statistical independence carries an important clinical message: a child with no family history of cardiovascular disease who follows an obese BMI trajectory is not protected from the cardiovascular consequences of childhood obesity. Excess adiposity in childhood appears to be a risk factor in its own right, not merely a marker that matters only in genetically susceptible families.

The magnitude of the associations was substantial. In models adjusted for parental cardiovascular disease, and compared with children following the average BMI trajectory, females on the overweight trajectory had a 65 percent higher hazard of coronary heart disease at ages 25 to 44 years, with a hazard ratio of 1.65 and a 95 percent confidence interval of 1.21 to 2.26. Females on the obesity trajectory fared worse still, with a hazard ratio of 2.28, meaning their hazard of early-onset disease was more than doubled. The corresponding estimates for males were strikingly similar: 1.70 for the overweight trajectory and 2.23 for the obesity trajectory, both statistically significant. These are large effects for a risk factor measurable in childhood, decades before any symptoms appear.

The age-stratified analysis revealed a pattern with real biological and public health significance. The elevated hazards were concentrated in the youngest age bands. Among both sexes, associations were strongest and clearest at ages 25 to 44 years. Among males, the associations remained evident at ages 45 to 54 years, but by age 55 and beyond, no associations between childhood BMI trajectory and coronary heart disease were found in either sex. This fading of the signal at older ages likely reflects the interplay of competing risks and the accumulation of other exposures across the life course. As people age, smoking, hypertension, diabetes, and adult weight change increasingly shape coronary risk, and the predictive power of childhood body size diminishes relative to these later-life factors. The finding underscores that childhood adiposity is a particularly potent driver of the early-onset form of the disease, precisely the form that is rising and that strikes people in the prime of working and family life.

The study’s conclusions land at a moment of global alarm over early-onset cardiovascular disease. Worldwide analyses have documented that cardiovascular disease remains the leading cause of death, and that rates of heart disease in younger adults have been climbing in many countries. At the same time, childhood obesity has surged: pooled analyses covering 222 million children and adolescents show that obesity has risen sharply since 1990, and in the United States the prevalence of obesity among children aged 2 to 19 has continued to increase through 2023. The Danish findings suggest these two trends are connected. If excess childhood adiposity more than doubles the hazard of coronary heart disease before middle age, then the current generation of children growing up with obesity may face a future wave of heart attacks and other coronary events occurring decades earlier than in their parents’ generation.

Mechanistically, the evidence that childhood obesity leaves lasting cardiovascular fingerprints is not new. Autopsy studies from the Bogalusa Heart Study, conducted decades ago, revealed fatty streaks and early atherosclerotic plaques in the coronary arteries of children and young adults, demonstrating that atherosclerosis begins in childhood. Subsequent cohort studies have linked childhood and adolescent BMI to cardiovascular mortality in midlife, to atrial fibrillation, to ischemic stroke, and to type 2 diabetes and obesity-related cancers. What the new study adds is the demonstration that this childhood risk is not contingent on family history. Children with obese BMI trajectories carry their risk with them regardless of the cardiovascular health of their parents, which strengthens the argument that childhood body size is an independent, modifiable determinant of lifelong cardiovascular health.

The public health implications are difficult to overstate. Clinical risk assessment has traditionally focused on middle-aged and older adults, and family history is often used to decide which younger patients deserve closer scrutiny. These results suggest that childhood BMI deserves a place in that conversation, and that prevention efforts aimed at childhood obesity are, in effect, coronary prevention campaigns with a lead time of several decades. Because the associations were independent of parental cardiovascular disease, interventions need not be targeted only at children with a family history; the entire population of children on elevated BMI trajectories stands to benefit. The authors emphasize that their findings highlight excess childhood adiposity as an important contributor to the early origins of coronary heart disease and reinforce the urgency of addressing the growing burden of childhood obesity. With early-onset cardiovascular disease on the rise worldwide, the trajectory a child’s BMI follows between the ages of 6 and 15 may quietly help determine whether that child, as an adult, becomes one of the growing number of people struck by heart disease in the prime of life.

Subject of Research: Childhood BMI trajectories and early-onset coronary heart disease risk

Article Title: Are associations of childhood body mass index trajectories with early-onset coronary heart disease modified by parental history of cardiovascular disease?

Article References: Aarestrup, J., Andersen, E. W., Twig, G., Jacobsen, R. K., Johnson, W., Bjerregaard, L. G., & Baker, J. L. (2026). Are associations of childhood body mass index trajectories with early-onset coronary heart disease modified by parental history of cardiovascular disease?. International Journal of Obesity. https://doi.org/10.1038/s41366-026-02239-4

Image Credits: AI Generated

DOI: 10.1038/s41366-026-02239-4

Keywords: childhood obesity, body mass index, coronary heart disease, early-onset cardiovascular disease, parental history, Copenhagen School Health Records Register, BMI trajectories, epidemiology, cohort study, risk factors, cardiovascular prevention, Denmark