The regulation-of-autophagy pathway may influence Chinese stature variation: evidence from elder adults

J Hum Genet. 2010 Jul;55(7):441-7. doi: 10.1038/jhg.2010.44. Epub 2010 May 7.

Abstract

Recent success of genome-wide association studies (GWASs) on human height variation emphasized the effects of individual loci or genes. In this study, we used a developed pathway-based approach to further test biological pathways for potential association with stature, by examining approximately 370,000 single-nucleotide polymorphisms (SNPs) across the human genome in 618 unrelated elder Han Chinese. A total of 626 biological pathways annotated by any of the three major public pathway databases (KEGG, BioCarta and Ambion GeneAssist Pathway Atlas) were tested. The regulation-of-autophagy (ROA) (nominal P=0.012) pathway was marginally significantly associated with human stature after our family wise error rate multiple-testing correction. We also used 1000 random recruited US whites for further replication. Interestingly, the ROA pathway presented the strongest signals in whites for height variation (nominal P=0.002). The results correspond to biological roles of the ROA pathway in human long bone development and growth. Our findings also implied that multiple-genetic factors may work jointly as a functional unit (pathway), and the traditional GWASs could have missed important genetic information imbedded in those less significant markers.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Asian People / genetics*
  • Autophagy / genetics*
  • Body Height / genetics*
  • China
  • Chromosomes, Human, Pair 9 / genetics
  • Female
  • Genetic Variation*
  • Haplotypes / genetics
  • Humans
  • Male
  • Metabolic Networks and Pathways / genetics*
  • Physical Chromosome Mapping
  • Polymorphism, Single Nucleotide / genetics
  • Vereinigte Staaten
  • White People / genetics