By Lisa Rapaport

(Reuters Health) – Standing above the crowd puts people at greater risk of developing varicose veins, a large genetic study suggests.

Varicose veins are swollen, twisted veins that can be seen just under the surface of the skin, usually in the legs. More than 30 million people in the U.S. have varicose veins. Although the condition is often dismissed as nothing more than a cosmetic nuisance, it can cause moderate pain and has been linked to the more serious side effect of deep vein thrombosis, or blood clots in the deep veins in the body.

For the current study, researchers analyzed data on almost 500,000 people participating in the long-term UK Biobank study, looking for traits associated with risk for varicose veins, and height stood out as a strong, independent risk factor.

They followed this with a genome-wide scan of several hundred thousand people that identified 30 genetic locations, many of them involved in skeletal and blood vessel development, which further suggest tallness may be a direct cause of varicose veins.

“We do not yet know why height is such a strong risk factor for varicose veins,” said senior study author Dr. Nicholas Leeper of Stanford University in California.

“It may be a simple matter of plumbing and gravity, with taller individuals experiencing higher pressures in their veins, causing them to enlarge and dilate,” Leeper said by email. “On the other hand, the powerful genetics studies we conducted showed that height is not only associated with disease, but also seems to be causal for disease – an important distinction, because the genes that regulate human height could have a role in the structure and integrity of the veins.”

The analysis used machine learning to search Biobank participants’ data for patterns linking varicose veins with other traits and confirmed that well-known risk factors – including being older, female, overweight or pregnant, or having a history of deep vein thrombosis – are all associated with varicose veins.

Surgery on the legs, family history, lack of movement, smoking and hormone therapy are also risk factors for varicose veins, the study confirmed.

But the connection between height and varicose veins was new and unexpected.

Comparing the tallest 25 percent of people to the shortest, the analysis showed the tallest had 74 percent higher risk of varicose veins, according to the results in Circulation.

In addition, researchers screened for genetic markers associated with varicose veins in 337,536 people, 9,577 of whom had varicose vein disease. The resulting 30 locations on the genome provide new leads for researchers to investigate the mechanisms involved in varicose vein development and risk, the authors note.

One limitation of the study is that the participants in the UK Biobank might not reflect what would happen in populations in other parts of the world.

Still, it offers some of the most comprehensive insight to date into the environmental and biological factors that might influence the risk of varicose veins, said Dr. Quinn Wells, of Vanderbilt University Medical Center in Nashville, Tennessee.

“Although findings of this study may not immediately impact patient care, understanding these factors is the first step toward developing effective interventions for prevention and treatment of varicose veins,” Wells, who wrote an accompanying editorial, said by email.

Generally, people can help prevent varicose veins by maintaining a healthy body weight and exercising to improve muscle strength and circulation, Wells advised.

“People should also avoid periods of uninterrupted standing or sitting, and if prolonged standing is unavoidable (e.g., for a job), they could consider wearing compression stockings to help keep blood from pooling in the legs,” Wells said. “Once varicose veins develop, the measures above can help prevent them from getting worse and help with discomfort.”

SOURCE: and Circulation, online September 24, 2018.