Genes for osteoporosis

Sep 21 2007

Researchers at Hebrew SeniorLife's Institute for Aging Research (IFAR) have examined close to 100,000 genetic markers for low bone mass and aging to help determine which genes are responsible for the development of osteoporosis and longevity.

One of the HSL studies surveyed the entire human genome (all the genetic material in a living organism), called a genome-wide association study (GWAS), to look for common genetic variations in hereditary osteoporosis traits, such as bone mineral density.

“We've examined nearly 100,000 genetic markers,” says Douglas Kiel, M.D., M.P.H., director of medical research at IFAR and co-author of two of the papers, “We're using this data and bone measurements over the years to see if bone mass is associated with certain genetic markers. We're looking for the genes for osteoporosis.”

The other study, conducted by HSL investigators in collaboration with Boston University colleagues, took a GWAS approach to detecting genes related to longevity and aging traits. Two candidates are FOXO1a, which is associated with age at death, and PON1, which is associated with age at death and illness-free survival. These findings, if replicated in others studies, may help scientists understand better the mechanisms responsible for aging and, in turn, aid in health promotion and disease prevention.

The studies, published as part of a 17-paper supplement to the online, open-access journal BMC Medical Genetics, examined the genetic differences that potentially affect the risk for certain diseases, using data collected from the landmark Framingham Heart Study (FHS).

The studies evaluated DNA at 100,000 sites along the human genome where people are known to commonly differ. Researchers then looked for associations between the genotypes (the genetic makeup encoded in an individual's DNA) and hundreds of clinical phenotype measures (observable, physical characteristics) from nearly 60 years of FHS data, including biomarkers for cardiovascular disease, cancer, osteoporosis, longevity and aging, and renal and endocrine function, among others.

In addition to BMC Medical Genetics, the results of the studies are also available through an online database of genotypes and phenotypes (http://view/ncbi.nlm.nih.gov/dbgap), which provides a number of electronic enhancements for viewing and examining the data, such as enabling users to drill down for precise details on all associations and allowing the data to be explored in the context of other National Center for Biotechnology Information genomic resources.

“It is important to remember,” says David Karasik, Ph.D., an associate scientist at IFAR and co-author of the HSL papers, “that we need to replicate our findings in other studies. We haven't found the genes for osteoporosis and aging, but we've generated a hypothesis for future work.”

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