A variant in MCF2L is associated with osteoarthritis

Am J Hum Genet. 2011 Sep 9;89(3):446-50. doi: 10.1016/j.ajhg.2011.08.001. Epub 2011 Aug 25.

Abstract

Osteoarthritis (OA) is a prevalent, heritable degenerative joint disease with a substantial public health impact. We used a 1000-Genomes-Project-based imputation in a genome-wide association scan for osteoarthritis (3177 OA cases and 4894 controls) to detect a previously unidentified risk locus. We discovered a small disease-associated set of variants on chromosome 13. Through large-scale replication, we establish a robust association with SNPs in MCF2L (rs11842874, combined odds ratio [95% confidence interval] 1.17 [1.11-1.23], p = 2.1 × 10(-8)) across a total of 19,041 OA cases and 24,504 controls of European descent. This risk locus represents the third established signal for OA overall. MCF2L regulates a nerve growth factor (NGF), and treatment with a humanized monoclonal antibody against NGF is associated with reduction in pain and improvement in function for knee OA patients.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Chromosomes, Human, Pair 13 / genetics*
  • European Continental Ancestry Group / genetics
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study
  • Guanine Nucleotide Exchange Factors / genetics*
  • Guanine Nucleotide Exchange Factors / metabolism
  • Humans
  • Nerve Growth Factor / immunology
  • Nerve Growth Factor / metabolism
  • Odds Ratio
  • Osteoarthritis / genetics*
  • Osteoarthritis / immunology
  • Polymorphism, Single Nucleotide / genetics
  • Rho Guanine Nucleotide Exchange Factors

Substances

  • Antibodies, Monoclonal
  • Guanine Nucleotide Exchange Factors
  • MCF2L protein, human
  • Rho Guanine Nucleotide Exchange Factors
  • Nerve Growth Factor