The regulation-of-autophagy pathway may influence Chinese stature variation: evidence from elder adults.
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.
Pan
Feng
F
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Liu
Xiao-Gang
XG
Guo
Yan-Fang
YF
Chen
Yuan
Y
Dong
Shan-Shan
SS
Qiu
Chuan
C
Zhang
Zhi-Xin
ZX
Zhou
Qi
Q
Yang
Tie-Lin
TL
Guo
Yan
Y
Zhu
Xue-Zhen
XZ
Deng
Hong-Wen
HW
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001343:Autophagy / Q000235:genetics*; D001827:Body Height / Q000235:genetics*; D002681:China; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D020161:Physical Chromosome Mapping; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014481:United States; D044465:White People / Q000235:genetics
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