The genetics of low and high birthweight and their relationship with cardiometabolic disease
Authors' conclusion
Our results underscore the importance of genetic factors in the genesis of the phenotypic correlation between birthweight and cardiometabolic traits and diseases.
Study context
- Population
- UK Biobank participants with birthweight data
- Participants
- 20,947 / 12,715 / 207,506
- Comparison
- Low (<2.5 kg) and high (>4.5 kg) birthweight vs controls; full-range, truncated and winsorised continuous genome-wide association studies (GWAS) of birthweight
- Low birthweightn = 20,947
- High birthweightn = 12,715
- Controlsn = 207,506reference
- Outcome
- Genetic correlation (rG) with birthweight within the normal range
Methodological detailscase-control GWAS, continuous GWAS (full-range, truncated, winsorised), bivariate linkage disequilibrium (LD) score regression, REGENIE software
- Case-control GWAS
- Continuous GWAS (full-range, truncated, winsorised)
- Bivariate LD score regression
- REGENIE software
Main finding
As reported in the abstract
High birthweight: mostly similar genetic aetiology to normal-range birthweight, rG
0.91 (0.83, 0.99) (95% CI)
Low birthweight: more evidence for a separate set of genes, rG
−0.74 (0.66, 0.82) (95% CI)
Observational data: associations, not effects.
Further findings
Independent genome-wide significant associations (p<5×10-8): winsorised vs truncated GWAS
- Truncated GWAS
- 120 variants at 94 loci
- Winsorised GWAS (best locus detection)
- 270 variants at 178 loci
- Not identified in previous birthweight GWAS
- 27 variants at 25 loci
Novel low-frequency missense variant in ABCC8 (gene involved in congenital hyperinsulinism, neonatal DM and MODY)
- Estimated increase in birthweight amongst carriers
- 170 g
Original publication
The genetics of low and high birthweight and their relationship with cardiometabolic disease. Diabetologia. Published 10 April 2025. doi:10.
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