A genetic analysis of 6,669 people in Finland and the Mediterranean island of Sardinia uncovered genetic variations affecting height, which Dr. Eric Boerwinkle of the University of Texas Health Science Center at Houston extended to evaluate their impact on height in the United States population. The variants are in a region of the genome previously associated with a common type of arthritis.

Dr. Boerwinkle, along with Dr. Francis S. Collins of the National Human Genome Research Institute (NHGRI), and other co-investigators used a relatively new research tool called a genome-wide association study to reach findings published in the January 13 online edition of the journal Nature Genetics.

“We took the genetic variations found in these special populations and established their impact on the general U.S. population,” Dr. Boerwinkle said. “We found the genetic variations in white Americans and African-Americans.” The genetic variants may affect height by about an eighth of an inch.

Dr. Boerwinkle conducted follow-up tests on 15,565 people in four U.S. communities enrolled in a prospective population study he oversees called the Atherosclerosis Risk in Communities Study (ARIC).  “Height is highly hereditary,” he said. “This study is one of the first genome-wide association studies to investigate height.”

A genome-wide association study, according to Dr. Boerwinkle, enables scientists to survey each participant’s complete set of DNA, or genome, by looking for strategically selected markers of genetic variation. “None of this research would have been possible in the past,” he said. As a result of genome-wide association studies, researchers around the globe have associated more than 60 common DNA variants with the risk of more than 20 common diseases or related traits.

The variants most strongly associated with height in the new genome-wide association study are in a region of the 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 in Asian and European populations.

“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 Dr. Karen L. Mohlke, an assistant professor of genetics at the University of North Carolina at Chapel Hill. “Our findings suggest a link between the genetic basis of height and osteoarthritis, potentially mediated through alterations in bone growth and development.”

The genetic variants account for a small fraction of the genetic basis of height, according to Dr. Boerwinkle. A variety of factors, including genetics, prenatal environment and diet, interact to determine how tall someone grows. Genetic factors are thought to be responsible for at least 80 percent of the variation in height among people. However, the new genetic variants, plus ones identified in an earlier study, together account for less than 1 percent of human height variation.

“Many of the genetic variants involved in height likely will have only small effects, so it’s going to take a lot of work involving very large sample sets to uncover all of them,” Dr. Collins said.

Dr. Boerwinkle is director of the Center for Human Genetics at The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM), a part of the UT Health Science Center at Houston, the Kozmetsky Family Chair in Human Genetics and director of the Human Genetics Center at the University of Texas School of Public Health.

The study received support from the National Institutes of Health (NIH).

The Nature Genetics article is titled “Common Variants in the GDF5-BFZB Region Are Associated with Variation in Human Height.”