Gestational diabetes & diabetes in pregnancy
Mendelian randomization identifies age at menarche as an independent causal effect factor for gestational diabetes mellitus
Authors' conclusion
Genetic variants predisposing individuals to early AAM were independently associated with higher GDM risk. Further research is required to understand the mechanisms underlying this putative causative association. In addition, AAM may be helpful in clinical practice to identify women at risk for GDM; pregnant women who are young for menarche may need to take precautions before GDM develops.
Study context
- Population
- Individuals of European descent (GWAS); Gestational diabetes mellitus (GDM) summary-level data from UK BiobankGDM summary data
- Participants
- 123,579 individuals
- Comparison
- Genetically predicted age at menarche (AAM) vs GDM risk
- Outcome
- GDM risk (inverse-variance-weighted MR analysis)
Methodological detailsunivariable and multivariable Mendelian randomization (MR), inverse-variance-weighted primary analysis, MR-Egger, heterogeneity, pleiotropy and leave-one-out sensitivity analyses, MR-Steiger directionality test
- Univariable and multivariable MR
- Inverse-variance-weighted primary analysis
- MR-Egger, heterogeneity, pleiotropy and leave-one-out sensitivity analyses
- MR-Steiger directionality test
Main finding
As reported in the abstract
Genetically predicted early AAM causally associated with higher GDM risk: OR (95% CI), p
0.798
0.649–0.980p = .031
Further findings
AAM and GDM risk, multivariable MR adjusted for oestradiol, sex hormone-binding globulin (SHBG) and bioavailable testosterone (BioT)
- OR (95% CI), p
- 0.651 (0.481-0.881), p = .006
- Multivariable MR
SHBG and BioT (per 1-SD increase) and GDM risk, univariable MR
- SHBG: decrease in GDM risk, p = 3.71E-05
- 41.4%
- BioT: increase in GDM risk, p = .040
- 20.8%
SHBG, BioT and oestradiol and GDM risk, multivariable MR
- No direct causal effect of SHBG (adjusted for AAM, oestradiol, BioT), p
- P = 0.084
- No direct causal effect of BioT (adjusted for AAM, oestradiol, SHBG), p
- P = 0.533
- No direct causal association of oestradiol with GDM risk in univariable or multivariable MR
Original publication
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