Lifelong impacts of puberty timing on human plasma metabolic profiles: A metabolome‐wide Mendelian randomization study
Authors' conclusion
In summary, our study provides compelling evidence that puberty timing has a causal influence on certain plasma metabolites, although this influence is largely mediated by adulthood adiposity.
Study context
- Population
- Genome-wide association studies (GWAS) summary data: puberty timing from ReproGen Consortium (329,345 women of European ancestry); 174 plasma metabolites from cross-platform GWAS of up to 86,507 participants (Fenland, EPIC-Norfolk, INTERVAL and three public studies)
- Comparison
- Genetically predicted puberty timing and 174 plasma metabolites
- Outcome
- Causal effect of puberty timing on 174 plasma metabolites
Methodological detailsmetabolome-wide, two-step Mendelian randomization (MR), multivariable MR (multivariable Mendelian randomization (MVMR)), replication in UK Biobank
- Metabolome-wide
- Two-step MR
- Multivariable MR (MVMR)
- Replication in UK Biobank
Main finding
As reported in the abstract
Plasma metabolites causally affected by puberty timing (two-sample MR)
Metabolites with moderate evidence of a causal relationship (7 acylcarnitines, 8 amino acids, 2 biogenic amines, 6 lysophosphatidylcholines)
23 of 174
Further findings
Causal effects after excluding SNPs associated with birth weight and childhood adiposity
- Metabolites with persisting causal effects (8 acylcarnitines, 4 amino acids, 2 biogenic amines, 2 lysophosphatidylcholines)
- 16
Mediation by adulthood adiposity (two-step MR)
- Relationship between puberty timing and plasma metabolites mediated by adulthood adiposity
Independent causal effect of puberty timing (MVMR)
- Metabolites with moderate evidence of an independent causal effect (5 acylcarnitines, 2 amino acids, 1 biogenic amine, 1 lysophosphatidylcholine, 1 phosphatidylcholine)
- 10
Replication (UK Biobank)
- Replication analysis suggested robustness of results
Original publication
Lifelong impacts of puberty timing on human plasma metabolic profiles: A metabolome‐wide Mendelian randomization study. Diabetes Obes Metab. Published 14 October 2024. doi:10.
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