GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI

Sci Adv. 2019 Sep 4;5(9):eaaw3095. doi: 10.1126/sciadv.aaw3095. eCollection 2019 Sep.

Abstract

Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adult
  • Body Mass Index*
  • Child
  • Female
  • Genetic Association Studies*
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Genomics
  • Growth Charts
  • Humans
  • Infant
  • Intracellular Signaling Peptides and Proteins
  • Longitudinal Studies
  • Male
  • Pharmacogenomic Variants
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci*
  • Quantitative Trait, Heritable*
  • Receptors, Leptin / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • Intracellular Signaling Peptides and Proteins
  • LEPR protein, human
  • LEPROT protein, human
  • Receptors, Leptin