title: A common variant of ubiquinol-cytochrome c reductase complex is associated with DDH.
abstract: OBJECTIVE
  Genetic basis of Developmental dysplasia of the hip (DDH) remains largely unknown. To find new susceptibility genes for DDH, we carried out a genome-wide association study (GWAS) for DDH.
  
  
  METHODS
  We enrolled 386 radiology confirmed DDH patients and 558 healthy controls (Set A) to conduct a genome-wide association study (GWAS). Quality-control was conducted at both the sample and single nucleotide polymorphism (SNP) levels. We then conducted a subsequent case-control study to replicate the association between a promising loci, rs6060373 in UQCC gene and DDH in an independent set of 755 cases and 944 controls (set B).
  
  
  RESULTS
  In the DDH GWAS discovering stage, 51 SNPs showed significance of less than 10-4, and another 577 SNPs showed significance of less than 10-3. In UQCC, all the 12 genotyped SNPs showed as promising risk loci. Genotyping of rs6060373 in set A showed the minor allele A as a promising risk allele (p = 4.82*10-7). In set A, the odds ratio of allele A was 1.77. Genotyping of rs6060373 in Set B produced another significant result (p = 0.0338) with an odds ratio of 1.18 for risk allele A. Combining set A and set B, we identified a total p value of 3.63*10-6 with the odds ratio of 1.35 (1.19-1.53) for allele A.
  
  
  CONCLUSIONS
  Our study demonstrates common variants of UQCC, specifically rs6060373, are associated with DDH in Han Chinese population.
authors.affiliation: The Center of Diagnosis and Treatment for Joint Disease, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, Jiangsu 210008, China; Laboratory for Bone and Joint Diseases, Model Animal Research Center, Nanjing University, Nanjing, Jiangsu 210061, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Sun
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, Jiangsu 210061, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: The Center of Diagnosis and Treatment for Joint Disease, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, Jiangsu 210008, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Hao
authors.affiliation: The Center of Diagnosis and Treatment for Joint Disease, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, Jiangsu 210008, China; Laboratory for Bone and Joint Diseases, Model Animal Research Center, Nanjing University, Nanjing, Jiangsu 210061, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Dai
authors.affiliation: The Center of Diagnosis and Treatment for Joint Disease, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, Jiangsu 210008, China.
authors.forename: Dongyang
authors.initials: D
authors.lastname: Chen
authors.affiliation: The Center of Diagnosis and Treatment for Joint Disease, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, Jiangsu 210008, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Xu
authors.affiliation: The Center of Diagnosis and Treatment for Joint Disease, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, Jiangsu 210008, China; Laboratory for Bone and Joint Diseases, Model Animal Research Center, Nanjing University, Nanjing, Jiangsu 210061, China.
authors.forename: Dongquan
authors.initials: D
authors.lastname: Shi
authors.affiliation: The Center of Diagnosis and Treatment for Joint Disease, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, Jiangsu 210008, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Mao
authors.affiliation: Laboratory for Bone and Joint Diseases, Model Animal Research Center, Nanjing University, Nanjing, Jiangsu 210061, China.
authors.forename: Huajian
authors.initials: H
authors.lastname: Teng
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, Jiangsu 210061, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
authors.affiliation: The Center of Diagnosis and Treatment for Joint Disease, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, Jiangsu 210008, China; Laboratory for Bone and Joint Diseases, Model Animal Research Center, Nanjing University, Nanjing, Jiangsu 210061, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Jiang
mesh_terms: D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006618:Hip Dislocation, Congenital / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
chemical_list: D008565:Membrane Proteins; C582875:UQCC1 protein, human
references.citation: J Clin Invest. 2000 Apr;105(8):1085-93
references.pmid: 10772653
references.citation: Mech Dev. 2001 Jan;100(1):123-5
references.pmid: 11118897
references.citation: Ann Hum Genet. 2000 Jan;64(Pt 1):51-9
references.pmid: 11246461
references.citation: Development. 2001 Jun;128(11):2119-29
references.pmid: 11493533
references.citation: Biol Soc. 1987 Jun;4(2):61-77
references.pmid: 12314923
references.citation: Arthritis Rheum. 2003 Mar;48(3):700-8
references.pmid: 12632423
references.citation: Exp Cell Res. 2003 Aug 1;288(1):35-50
references.pmid: 12878157
references.citation: J Gene Med. 2004 Feb;6(2):238-45
references.pmid: 14978777
references.citation: Clin Orthop Relat Res. 1964 Mar-Apr;33:119-28
references.pmid: 5889015
references.citation: J Biol Chem. 1989 Jul 5;264(19):11122-30
references.pmid: 2544586
references.citation: Arch Dis Child Fetal Neonatal Ed. 1997 Mar;76(2):F94-100
references.pmid: 9135287
references.citation: Rheumatology (Oxford). 2005 Feb;44(2):211-8
references.pmid: 15479751
references.citation: Cell Res. 2005 Feb;15(2):97-8
references.pmid: 15740637
references.citation: J Cell Biochem. 2005 Dec 1;96(5):888-96
references.pmid: 16149058
references.citation: J Cell Biochem. 2006 Jan 1;97(1):33-44
references.pmid: 16215986
references.citation: PLoS Biol. 2006 Mar;4(3):e72
references.pmid: 16494531
references.citation: Nat Genet. 2008 Feb;40(2):198-203
references.pmid: 18193045
references.citation: Pediatr Int. 2008 Jun;50(3):341-5
references.pmid: 18533949
references.citation: Nat Genet. 2008 Aug;40(8):994-8
references.pmid: 18622395
references.citation: Arthritis Res Ther. 2008;10(5):R126
references.pmid: 18947434
references.citation: Arthritis Rheum. 2009 Jul;60(7):2019-27
references.pmid: 19565481
references.citation: Osteoarthritis Cartilage. 2010 Dec;18(12):1592-5
references.pmid: 20887794
references.citation: Ann Rheum Dis. 2011 May;70(5):873-5
references.pmid: 20870806
references.citation: Int J Epidemiol. 2011 Jun;40(3):731-9
references.pmid: 21233139
references.citation: Arthritis Res Ther. 2011;13(1):R27
references.pmid: 21329514
references.citation: Osteoarthritis Cartilage. 2012 Jan;20(1):60-3
references.pmid: 22037112
references.citation: Bone. 2013 Mar;53(1):129-33
references.pmid: 23207799
references.citation: Nat Genet. 2013 Jun;45(6):676-9
references.pmid: 23666238