Exome sequencing and subsequent association studies identify five amino acid-altering variants influencing human height

Hum Genet. 2012 Mar;131(3):471-8. doi: 10.1007/s00439-011-1096-4. Epub 2011 Sep 29.


Height is a highly heritable trait that involves multiple genetic loci. To identify causal variants that influence stature, we sequenced whole exomes of four children with idiopathic short stature. Ninety-five nonsynonymous single-nucleotide polymorphisms (nsSNPs) were selected as potential candidate variants. We performed association analysis in 740 cohort individuals and identified 11 nsSNPs in 10 loci (DIS3L2, ZBTB38, FAM154A, PTCH1, TSSC4, KIF18A, GPR133, ACAN, FAM59A, and NINL) associated with adult height (P < 0.05), including five novel loci. Of these, two nsSNPs (TSSC4 and KIF18A loci) were significant at P < 0.05 in the replication study (n = 1,000) and five (ZBTB38, FAM154A, TSSC4, KIF18A, and FAM59A loci) were significant at P < 0.01 in the combined analysis (n = 1,740). Together, the five nsSNPs accounted for approximately 2.5% of the height variation. This study demonstrated the utility of next-generation sequencing in identifying genetic variants and loci associated with complex traits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Body Height / genetics*
  • Exome*
  • Female
  • Gene Expression Profiling
  • Genome, Human
  • Growth Disorders / genetics
  • Humans
  • Korea
  • Male
  • Polymorphism, Single Nucleotide*
  • Sequence Analysis, DNA