title: The regulation-of-autophagy pathway may influence Chinese stature variation: evidence from elder adults.
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.
authors.affiliation: 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.
authors.forename: Feng
authors.initials: F
authors.lastname: Pan
authors.forename: Xiao-Gang
authors.initials: XG
authors.lastname: Liu
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Guo
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Dong
authors.forename: Chuan
authors.initials: C
authors.lastname: Qiu
authors.forename: Zhi-Xin
authors.initials: ZX
authors.lastname: Zhang
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.forename: Tie-Lin
authors.initials: TL
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.forename: Xue-Zhen
authors.initials: XZ
authors.lastname: Zhu
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: 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
references.citation: Bioinformatics. 2009 Dec 15;25(24):3275-81
references.pmid: 19837719
references.citation: Rheumatol Int. 2008 Jun;28(8):737-41
references.pmid: 18172652
references.citation: Methods Mol Biol. 2009;563:289-301
references.pmid: 19597792
references.citation: Hum Mol Genet. 2009 Sep 15;18(18):3516-24
references.pmid: 19570815
references.citation: BMC Bioinformatics. 2009 Dec 18;10:429
references.pmid: 20021635
references.citation: Nat Genet. 2008 May;40(5):575-83
references.pmid: 18391952
references.citation: Nat Genet. 2007 Oct;39(10):1245-50
references.pmid: 17767157
references.citation: Bone. 2008 Jul;43(1):7-18
references.pmid: 18486584
references.citation: Bioinformatics. 2009 Oct 15;25(20):2762-3
references.pmid: 19620097
references.citation: Am J Hum Genet. 2007 Dec;81(6):1278-83
references.pmid: 17966091
references.citation: Cells Tissues Organs. 2009;189(1-4):88-92
references.pmid: 18703865
references.citation: Nat Genet. 2008 May;40(5):584-91
references.pmid: 18391950
references.citation: J Hum Genet. 2004;49(3):148-153
references.pmid: 14991526
references.citation: Hum Genet. 2009 Feb;125(1):1-9
references.pmid: 19030899
references.citation: Am J Hum Genet. 2009 Mar;84(3):399-405
references.pmid: 19249008
references.citation: Hum Mol Genet. 2009 May 1;18(9):1661-9
references.pmid: 19039035
references.citation: Eur J Hum Genet. 2010 Jan;18(1):111-7
references.pmid: 19584899
references.citation: Bone. 2010 Jan;46(1):129-36
references.pmid: 19786129
references.citation: J Cell Biochem. 1999 Sep 1;74(3):372-85
references.pmid: 10412039
references.citation: Hum Mol Genet. 2009 Jan 15;18(2):373-80
references.pmid: 18952825
references.citation: Trends Genet. 2008 Dec;24(12):595-603
references.pmid: 18950892
references.citation: Int J Oncol. 2007 Feb;30(2):469-76
references.pmid: 17203230
references.citation: Autophagy. 2006 Jul-Sep;2(3):215-6
references.pmid: 16874108
references.citation: Biometrics. 2005 Mar;61(1):186-92
references.pmid: 15737092
references.citation: Am J Hum Genet. 2007 Sep;81(3):559-75
references.pmid: 17701901
references.citation: Nat Genet. 2006 Aug;38(8):904-9
references.pmid: 16862161
references.citation: Cell Cycle. 2009 Feb 1;8(3):391-3
references.pmid: 19177014
references.citation: Genetics. 2000 Jun;155(2):945-59
references.pmid: 10835412
references.citation: Am J Hum Genet. 2008 Oct;83(4):529-34
references.pmid: 18940313
references.citation: PLoS Genet. 2007 Jun;3(6):e98
references.pmid: 17571925
references.citation: Apoptosis. 2004 May;9(3):265-77
references.pmid: 15258458
references.citation: Bioinformatics. 2009 Oct 1;25(19):2478-85
references.pmid: 19608708
references.citation: Cell. 2005 Jan 28;120(2):237-48
references.pmid: 15680329
references.citation: PLoS One. 2008 Jan 16;3(1):e1449
references.pmid: 18197259
references.citation: Nat Genet. 2008 May;40(5):609-15
references.pmid: 18391951