Genetic regulation of adult stature

Curr Opin Pediatr. 2009 Aug;21(4):515-22. doi: 10.1097/MOP.0b013e32832c6dce.

Abstract

Purpose of review: Both environmental (e.g., nutrition) and genetic factors contribute to adult height variation in the general population. However, heritability studies have shown that most of the variation in height is genetically controlled. Although height, a classic polygenic trait, has been studied for more than 100 years, the genetic factors that influence its variation remained, prior to 2007, unknown. The identification of genes that regulate human height would greatly enhance our understanding of human growth and height-associated human syndromes.

Recent findings: Genome-wide association studies have become a powerful tool to identify genes that are associated with complex human diseases and traits. Recent large meta-analyses of genome-wide association studies for height have yielded 47 loci robustly associated with height variation. The effect of each of these height single nucleotide polymorphisms is small, yet in aggregate they can correctly assign individuals to the lower or upper tail of the height distribution. Interestingly, some of these height loci include genes that have been previously implicated by Mendelian genetics in tall or short stature syndromes, confirming the hypothesis that genes that cause syndromes can also harbor common alleles with a weaker effect on stature. Finally, the recent findings highlight biological pathways (e.g., hedgehog signaling, microRNA, chromatin structure) involved in human growth.

Summary: This review summarizes the recent progress made using genome-wide association studies on the identification of common genetic variants that contribute to adult height variation in the general population.

Publication types

  • Review

MeSH terms

  • Adult
  • Animals
  • Body Height / genetics*
  • Gene Expression Regulation*
  • Growth Differentiation Factor 5 / genetics
  • HMGA2 Protein / genetics
  • Humans
  • Polymorphism, Single Nucleotide
  • Young Adult

Substances

  • GDF5 protein, human
  • Growth Differentiation Factor 5
  • HMGA2 Protein