ArticleProceedings of the National Academy of Sciences of the United States of America2015
Cohort of birth modifies the association between FTO genotype and BMI.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 2 of them syntheses that pooled it.
What it found
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Who cites it
42 citing papers in PubMed, 2 syntheses or guidelines pooled it, 113 citations in OpenAlex.
- Meta-regression of genome-wide association studies to estimate age-varying genetic effects.European journal of epidemiology · 2024Pooled it
- Deceased donor multidrug resistance protein 1 and caveolin 1 gene variants may influence allograft survival in kidney transplantation.Kidney international · 2015Pooled it
- Design and model choices shape inference of age-varying genetic effects on complex traits.Nature aging · 2026Article
- Genetic risk for high body mass index before and amidst the obesity epidemic: Cross-cohort analysis of four british birth cohort studies.PLoS genetics · 2026Article
- Epigenetics of Childhood Obesity.Hormone research in paediatrics · 2026Review
- Association of fetal FTO gene variants with maternal postload glucose levels in pregnancy.International journal of obesity (2005) · 2025Article
- Toward Responsible and Sustainable Data Sharing in Large-scale Cohort-based Genomic Research.Genomics, proteomics & bioinformatics · 2025Article
- Microevolutionary hypothesis of the obesity epidemic.PloS one · 2024Article
- Overweight grandsons and grandfathers' starvation exposure.Journal of health economics · 2023Article
- Exercise and Experiments of Nature.Comprehensive Physiology · 2023Article
- Genetic Effect on Body Mass Index and Cardiovascular Disease Across Generations.Circulation. Genomic and precision medicine · 2023Article
- Multi-omic analyses identify mucosa bacteria and fecal metabolites associated with weight loss after fecal microbiota transplantation.Innovation (Cambridge (Mass.)) · 2022Article
- Modeling Interaction and Dispersion Effects in the Analysis of Gene-by-Environment Interaction.Behavior genetics · 2022Article
- Interactions between Polygenic Scores and Environments: Methodological and Conceptual Challenges.Sociological science · 2020Article
- Development and change in attachment: A multiwave assessment of attachment and its correlates across childhood and adolescence.Journal of personality and social psychology · 2020Article
- Mendelian Randomization analysis of the causal effect of adiposity on hospital costs.Journal of health economics · 2020Article
- Association of a genetic risk score with BMI along the life-cycle: Evidence from several US cohorts.PloS one · 2020Article
- The "All of Us" Research Program.The New England journal of medicine · 2019Article
- Quantifying the impact of genes on body mass index during the obesity epidemic: longitudinal findings from the HUNT Study.BMJ (Clinical research ed.) · 2019Article
- Genetic determinants of BMI from early childhood to adolescence: the Santiago Longitudinal Study.Pediatric obesity · 2019Article
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
Abstract
A substantial body of research has explored the relative roles of genetic and environmental factors on phenotype expression in humans. Recent research has also sought to identify gene-environment (or g-by-e) interactions, with mixed success. One potential reason for these mixed results may relate to the fact that genetic effects might be modified by changes in the environment over time. For example, the noted rise of obesity in the United States in the latter part of the 20th century might reflect an interaction between genetic variation and changing environmental conditions that together affect the penetrance of genetic influences. To evaluate this hypothesis, we use longitudinal data from the Framingham Heart Study collected over 30 y from a geographically relatively localized sample to test whether the well-documented association between the rs993609 variant of the FTO (fat mass and obesity associated) gene and body mass index (BMI) varies across birth cohorts, time period, and the lifecycle. Such cohort and period effects integrate many potential environmental factors, and this gene-by-environment analysis examines interactions with both time-varying contemporaneous and historical environmental influences. Using constrained linear age-period-cohort models that include family controls, we find that there is a robust relationship between birth cohort and the genotype-phenotype correlation between the FTO risk allele and BMI, with an observed inflection point for those born after 1942. These results suggest genetic influences on complex traits like obesity can vary over time, presumably because of global environmental changes that modify allelic penetrance.
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