title: Genetic contribution to radiographic severity in osteoarthritis of the knee.
abstract: OBJECTIVE
  Knee osteoarthritis (OA) has a significant genetic component. The authors have assessed the role of three variants reported to influence risk of knee OA with p<5×10-8 in determining patellofemoral and tibiofemoral Kellgren Lawrence (K/L) grade in knee OA cases.
  
  
  METHODS
  3474 knee OA cases with sky-line and weight-bearing antero-posterior x-rays of the knee were selected based on the presentation of K/L grade ≥2 at either the tibiofemoral or patellofemoral compartments for one or both knees. Patients belonging to three UK cohorts, were genotyped for rs143383, rs4730250 and rs11842874 mapping to the GDF5, COG5 and MCF2L genes, respectively. The association between tibiofemoral K/L grade and patellofemoral K/L grade was assessed after adjusting for age, gender and body mass index.
  
  
  RESULTS
  No significant association was found between the rs4730250 and radiographic severity. The rs11842874 mapping to MCF2L was found to be nominally significantly associated with patellofemoral K/L grade as a quantitative trait (p=0.027) but not as a binary trait. The GDF5 single nucleotide polymorphism rs143383 was associated with tibiofemoral K/L grade (β=0.05 (95% CI 0.02 to 0.08) p=0.0011).
  
  
  CONCLUSIONS
  Our data indicate that within individuals affected by radiographic knee OA, OAGDF5 has a modest but significant effect on radiographic severity after adjustment for the major risk factors.
authors.affiliation: Correspondence to Dr Ana M Valdes, Kings College London, Twin Research Unit, St Thomas Hospital, Lambeth Palace Rd, London SE1 7EH, UK. ana.valdes@kcl.ac.uk
authors.forename: Ana M
authors.initials: AM
authors.lastname: Valdes
authors.forename: Sally
authors.initials: S
authors.lastname: Doherty
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Muir
authors.forename: Weiya
authors.initials: W
authors.lastname: Zhang
authors.forename: Rose A
authors.initials: RA
authors.lastname: Maciewicz
authors.forename: Margaret
authors.initials: M
authors.lastname: Wheeler
authors.forename: Nigel
authors.initials: N
authors.lastname: Arden
authors.forename: Cyrus
authors.initials: C
authors.lastname: Cooper
authors.forename: M
authors.initials: M
authors.lastname: Doherty
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics*; D000368:Aged; D005260:Female; D005838:Genotype; D055428:Growth Differentiation Factor 5 / Q000235:genetics*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D008297:Male; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011859:Radiography; D064067:Rho Guanine Nucleotide Exchange Factors; D012307:Risk Factors
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C115632:COG5 protein, human; C525893:GDF5 protein, human; D055428:Growth Differentiation Factor 5; D020662:Guanine Nucleotide Exchange Factors; C577400:MCF2L protein, human; D064067:Rho Guanine Nucleotide Exchange Factors