Genome-wide meta-analysis with 2,206,440 individuals identifies 322 novel risk loci for obesity
Authors' conclusion
We identified 345 genome-wide significant loci, including 322 novel loci for obesity. Based on 345 loci, we provided new biological insights to the etiology of obesity. Of clinical interest, we provided some potential targets and drug repurposing for obesity.
Study context
- Population
- European individuals; obesity cases and healthy controls
- Participants
- 98,421 vs 2,108,019
- Comparison
- Obesity cases vs healthy controls
- Obesity casesn = 98,421
- Healthy controlsn = 2,108,019reference
- Outcome
- Genome-wide significant obesity-associated loci
Methodological detailsEuropean
- European
Pooled result
As reported in the abstract
- Novel genome-wide significant obesity-associated loci identified
- 322
- Known loci replicated
- 23 of 32
- SNP-based heritability: common variants explain genetic risk for obesity
- 17.19 ± 0.59%
- MiXeR-predicted effective sample size explaining 90% of obesity-associated phenotypic variance
- 1.6 million
- Likely causal genes across 345 obesity-associated loci
- 2000
- Prioritized causal genes
- 410
Further pooled results
Tissue specificity enrichment
- Obesity-related causal genes mainly expressed in brain putamen basal ganglia, hippocampus, amygdala, substantia nigra and caudate basal ganglia
Genetic correlation and gene-set analyses
- Positive correlations with obesity: some brain diseases and mood (e.g., broad depression, neuroticism, mood swings), inflammatory and allergic diseases (e.g., asthma, spondyloarthritis, Hashimoto thyroiditis), CVD (e.g., hypertension, MI, coronary artery disease) and lung disease (e.g., interstitial lung disease, COPD, lung cancer)
Gene-drug interaction
- Obesity-associated genes overlapped with targets of current obesity medications; potential targets (e.g., GLP1R, SIGMAR1, MC4R) and drug repurposing (e.g., iloprost, flunarizine, edrophonium chloride)
Original publication
Genome-wide meta-analysis with 2,206,440 individuals identifies 322 novel risk loci for obesity. Int J Obes (Lond). Published 15 December 2025. doi:10.
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