Public release date: 15-Apr-2012 [ | E-mail | Share ]
Contact: Krista Conger kristac@stanford.edu 650-725-5371 Stanford University Medical Center
STANFORD, Calif. Thirty-two previously unidentified genetic regions associated with osteoporosis and fracture have been identified by a large, worldwide consortium of researchers, including Stanford Prevention Research Center chief John Ioannidis, MD, DSc. Variations in the DNA sequences in these regions confer either risk or protection from the bone-weakening disease. Many, but not all, of the regions encode proteins involved in pathways known to involve bone health.
The research shows that osteoporosis results from the combined contributions of dozens, if not hundreds, of genes. It also suggests many new avenues for anti-osteoporosis drug development.
"We're learning that the genetic architecture of disease is very complex," said Ioannidis, who is one of seven senior authors of the study and the methodological leader of the consortium. The research will be published online April 15 in Nature Genetics.
The unprecedented prospective meta-analysis which involved 17 genome-wide association studies, 180 researchers and more than 100,000 participants also identified six regions strongly correlated with the risk of fractures of the femur or lower back. However, the predictive power of the study for individuals is relatively low: Those with multiple risk-increasing variants are only about three to four times more likely than those with the fewest variants to have lower bone mineral density and experience fractures.
"As a result," said Ioannidis, "the next step of incorporating this information into basic patient care is not clear. Each variant conveys a small quantum of risk or benefit. We can't predict exactly who will or won't get a fracture."
Although factors such as body weight, build and gender are currently much more predictive of osteoporosis than any of the genetic variants identified in the study, the research identified many pathways involved in bone health. The biological relevance of the findings was confirmed by the fact that some of the pathways are already targeted by current anti-osteoporosis drugs. Other, previously unsuspected pathways will help researchers understand more about the disease and how to develop drugs to fight it.
The research belies recent frustration with the ability of genome-wide association studies, or GWAS, to live up to their early hype. When first introduced in 2005, many researchers predicted that GWAS a way of quickly scanning whole genomes for minute differences associated with disease occurrence would quickly identify critical mutations for many conditions. This optimistic assessment proved to be largely unfounded for complex conditions such as osteoporosis, type-2 diabetes and obesity, which likely involve the combined effects of many genes and environmental components.
This study suggests that the number of participants in most GWAS may need to be vastly expanded to render useful data.
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New genetic regions linked to bone-weakening disease and fractures, Stanford researcher says
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