title: Evaluation of the genetic overlap between osteoarthritis with body mass index and height using genome-wide association scan data.
abstract: OBJECTIVE
  Obesity as measured by body mass index (BMI) is one of the major risk factors for osteoarthritis. In addition, genetic overlap has been reported between osteoarthritis and normal adult height variation. We investigated whether this relationship is due to a shared genetic aetiology on a genome-wide scale.
  
  
  METHODS
  We compared genetic association summary statistics (effect size, p value) for BMI and height from the GIANT consortium genome-wide association study (GWAS) with genetic association summary statistics from the arcOGEN consortium osteoarthritis GWAS. Significance was evaluated by permutation. Replication of osteoarthritis association of the highlighted signals was investigated in an independent dataset. Phenotypic information of height and BMI was accounted for in a separate analysis using osteoarthritis-free controls.
  
  
  RESULTS
  We found significant overlap between osteoarthritis and height (p=3.3×10(-5) for signals with p≤0.05) when the GIANT and arcOGEN GWAS were compared. For signals with p≤0.001 we found 17 shared signals between osteoarthritis and height and four between osteoarthritis and BMI. However, only one of the height or BMI signals that had shown evidence of association with osteoarthritis in the arcOGEN GWAS was also associated with osteoarthritis in the independent dataset: rs12149832, within the FTO gene (combined p=2.3×10(-5)). As expected, this signal was attenuated when we adjusted for BMI.
  
  
  CONCLUSIONS
  We found a significant excess of shared signals between both osteoarthritis and height and osteoarthritis and BMI, suggestive of a common genetic aetiology. However, only one signal showed association with osteoarthritis when followed up in a new dataset.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Elliott
authors.forename: Kay
authors.initials: K
authors.lastname: Chapman
authors.forename: Aaron
authors.initials: A
authors.lastname: Day-Williams
authors.forename: Kalliope
authors.initials: K
authors.lastname: Panoutsopoulou
authors.forename: Lorraine
authors.initials: L
authors.lastname: Southam
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Lindgren
authors.forename: Nigel
authors.initials: N
authors.lastname: Arden
authors.forename: Nadim
authors.initials: N
authors.lastname: Aslam
authors.forename: Fraser
authors.initials: F
authors.lastname: Birrell
authors.forename: Ian
authors.initials: I
authors.lastname: Carluke
authors.forename: Andrew
authors.initials: A
authors.lastname: Carr
authors.forename: Panos
authors.initials: P
authors.lastname: Deloukas
authors.forename: Michael
authors.initials: M
authors.lastname: Doherty
authors.forename: John
authors.initials: J
authors.lastname: Loughlin
authors.forename: Andrew
authors.initials: A
authors.lastname: McCaskie
authors.forename: William E R
authors.initials: WE
authors.lastname: Ollier
authors.forename: Ashok
authors.initials: A
authors.lastname: Rai
authors.forename: Stuart
authors.initials: S
authors.lastname: Ralston
authors.forename: Mike R
authors.initials: MR
authors.lastname: Reed
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Spector
authors.forename: Ana M
authors.initials: AM
authors.lastname: Valdes
authors.forename: Gillian A
authors.initials: GA
authors.lastname: Wallis
authors.forename: Mark
authors.initials: M
authors.lastname: Wilkinson
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Zeggini
mesh_terms: D000328:Adult; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D001827:Body Height / Q000235:genetics*; D015992:Body Mass Index; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D009765:Obesity / Q000235:genetics*; D010003:Osteoarthritis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*
chemical_list: D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human