Study Connects Genetic Basis of Height and Arthritis

Posted January 14, 2008

In studies involving more than 35,000 people and a survey across the entire human genome, an international team supported in part by the National Institutes of Health (NIH) has found evidence that common genetic variants recently linked to osteoarthritis may also play a minor role in human height. The findings were released this week in the advance online publication of the journal Nature Genetics.

The variants most strongly associated with height in the new genome-wide association study lie in a region of the human genome thought to influence expression of a gene for growth differentiation factor 5 (GDF5), which is a protein involved in the development of cartilage in the legs and other long bones. Rare variants in the GDF5 gene have been associated with disorders of skeletal development, and more common variants recently have been tied to susceptibility to osteoarthritis of the hip and knees.

“The common variants we identified are associated with both short stature and, as described previously, increased risk of osteoarthritis,” said the study’s senior author Karen L. Mohlke, PhD, of the University of North Carolina, Chapel Hill.

Dr. Mohlke and her colleagues emphasized that the new variants account for just a small fraction of the genetic basis of height, which means much more research is needed before scientists can paint a complete picture of this complex human trait.

“It is very exciting to have powerful enough tools to succeed at this extremely difficult work. Our findings show how understanding the factors involved in human height may provide new insights into osteoarthritis and other musculoskeletal diseases,” said National Human Genome Research Institute (NHGRI) Director Francis S. Collins, MD, PhD.

Osteoarthritis is by far the most common type of arthritis, affecting nearly 21 million Americans. The degenerative joint disease, which primarily affects cartilage, is seen mostly among older people.

The researchers speculate that genetic variants that reduce production of the GDF5 protein may affect the amount of cartilage in the spine, the proportion of limbs and/or the angles of joints, resulting in both a modest decrease in height and increased susceptibility to osteoarthritis.

This article was adapted from a press release issued by the National Institutes of Heath/National Human Genome Research Institute.