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 ∼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.
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Acknowledgements
We thank two anonymous reviewers for their time and effort in helping us improve and clarify this manuscript. HWD was partially supported by grants from NIH (P50AR055081, R01AG026564, R01AR050496, RC2DE020756, R01AR057049 and R03TW008221) and Franklin D Dickson/Missouri Endowment. The study also benefited from grants from National Science Foundation of China, Huo Ying Dong Education Foundation, HuNan Province, Xi’an Jiaotong University and the Ministry of Education of China. This study was supported by NIH grants from R01 AR050496, R21 AG027110, R01 AG026564, P50 AR055081 and R21 AA015973.
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Pan, F., Liu, XG., Guo, YF. et al. The regulation-of-autophagy pathway may influence Chinese stature variation: evidence from elder adults. J Hum Genet 55, 441–447 (2010). https://doi.org/10.1038/jhg.2010.44
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DOI: https://doi.org/10.1038/jhg.2010.44
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