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Plasma proteome variation and its genetic determinants in children and adolescents

Lili Niu1,2,3, Sara Elizabeth Stinson4, Louise Aas Holm4,5

  • 1Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark.

Nature Genetics
|February 19, 2025
PubMed

Insights

Genetic factors, age, sex, and BMI significantly impact plasma protein levels in children and adolescents. These genetic influences on plasma proteome variation persist into adulthood, aiding in understanding cardiometabolic traits.

Area of Science:

  • Genetics
  • Proteomics
  • Pediatrics

Background:

  • Understanding plasma proteome variation in pediatric development is crucial.
  • Factors influencing protein levels during childhood and adolescence are not fully understood.

Purpose of the Study:

  • To investigate the influence of genetic variants, age, sex, and body mass index on plasma proteome variation in children and adolescents.
  • To identify causal genes for cardiometabolic traits using plasma protein quantitative trait loci (pQTLs).

Main Methods:

  • Quantitative mass spectrometry-based proteomics on plasma from 2,147 children and adolescents.
  • Analysis of protein level associations with genetic variants, age, sex, and BMI.
  • Mendelian randomization and colocalization analyses to identify causal genes.

Main Results:

  • Identified 1,216 proteins, with 70% associated with age, sex, BMI, or genetic factors.
  • Protein quantitative trait loci (pQTLs) regulated one-third of identified proteins.
  • Replication in additional pediatric and adult cohorts confirmed genetic effects on plasma protein levels from childhood to adulthood.
  • Identified 41 causal genes for 33 cardiometabolic traits.

Conclusions:

  • Genetic effects significantly shape plasma proteome variation throughout development, from childhood to adulthood.
  • Plasma protein QTLs are valuable for identifying drug targets and understanding cardiometabolic diseases.

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