According to a major genetic study, a person’s height may have an impact on their likelihood of developing a number of prevalent diseases in adulthood. Significant results include an association between height and increased risk of peripheral neuropathy and circulatory problems, as well as an association between height and decreased risk of coronary heart disease. The results appeared in the June 2, 2022 issue of the journal PLOS Genetics.
Dr. Sridharan Raghavan of the Eastern Colorado VA Health Care System, who led the study, described the results as “a significant contribution to understanding how height relates to clinical conditions from an epidemiological perspective.” More research is needed before the findings can lead to changes in clinical care, Raghavan says. However, the results highlight the association between altitude and clinical conditions that affect the lives of veterans, he explains. “The broad scope of our study yielded a catalog of clinical conditions associated with genetically predicted height. In other words, these are conditions for which height might be a risk factor or a protective factor, independent of other environmental conditions that They could also affect height and health.” Height is not usually considered a risk factor for disease. However, previous studies have found associations between a person’s height and their propensity to develop a number of health problems. It is not fully understood whether this link is biologically based or caused by other factors.
Part of a person’s adult height is determined by the genes they inherited from their parents. However, environmental aspects such as diet, socioeconomic position, and demographics (such as age or gender) also have an impact on final height. This is why finding a link between height and disease risk can be challenging. To explore this connection, VA researchers analyzed the genetic and medical data of more than 280,000 veterans enrolled in MVP. They compared this data with a list of 3,290 genetic variants associated with a height from a recent genomic analysis.
They found that risk levels for 127 different medical conditions can be linked to genetically predicted height in white patients. Since black patients are underrepresented in genetic studies, fewer data are available on this population. But in this analysis, the medical traits associated with height were generally consistent between black and white patients. About 21% of the Veterans in the MVP study were black. At least 48 of the links identified in white patients were also valid for black patients. All of the most significant findings — height is associated with a lower risk of coronary heart disease and an increased risk of atrial fibrillation, peripheral neuropathy, and circulatory disorders — were found in black and white participants, according to the researchers. Overall, genetically predicted height was linked to both lower and higher disease risk, depending on the condition. Being tall seems to protect people from cardiovascular problems. The study linked being taller with a lower risk of high blood pressure, high cholesterol and coronary heart disease. But the risk of atrial fibrillation was higher in the taller participants. These connections have been shown before in previous research.
On the other hand, most of the non-cardiovascular diseases considered in the study may be more likely among tall people. This was especially true for circulation conditions that affected the veins and peripheral neuropathy. Damage to nerves outside of the brain and spinal cord, especially in the extremities, is known as peripheral neuropathy. Higher altitude has been associated with poorer neural conduction and nerve problems in previous research. Using genetic tools to suggest an increased risk of nerve problems in tall people, the MVP study validates this connection.
The researchers established a connection between genetically predicted height and conditions such as neuropathy-related urinary retention and erectile dysfunction. Raghavan called the findings on peripheral neuropathy “particularly interesting.” He discussed this finding with clinical colleagues who often see patients with peripheral neuropathy. Raghavan’s colleagues confirmed that tall people often show the worst neuropathy, but they were not aware of other studies describing this association.
Conditions such as cellulite, skin abscesses, chronic leg ulcers, and osteomyelitis were also associated with height. Being tall also seems to increase the risk of circulatory conditions like varicose veins and thrombosis, blood clots in the veins. Height may also increase the risk of other conditions not related to neuropathy or circulation. Deformities of the toes and feet, conditions that could be caused by the increased weight-bearing of tall people, were more common in people whose genetics predicted they would be tall.
The study also showed that height increases the risk of asthma and non-specific nerve disorders in women, but not in men. Taken together, the results suggest that height may be an unrecognized but biologically important and immutable risk factor for several common conditions, particularly those that affect the extremities, according to the researchers. It may be helpful to consider a person’s height when assessing risk and disease surveillance, they say.
More work is needed before this research can be translated into clinical care, Raghavan says. “I think our findings are the first step toward disease risk assessment in the sense that we identified conditions for which altitude might actually be a risk factor,” he explains. “Future work will need to assess whether incorporating height into disease risk assessments can inform strategies to modify other risk factors for specific conditions.” Future work will also focus on possible mechanisms linking height to these health conditions.
Researchers from multiple VA health care centers participated in the study, including, but not limited to, Dr. Tim Assimes of the Palo Alto VA Health Care System; Dr. Yan Sun of the Atlanta VA Medical Center; and Dr. Chris O’Donnell, one of the national MVP leaders, formerly with VA Boston Healthcare System and now with Novartis. MVP is a national research program to learn how genes, lifestyle, and military exposures affect health and disease. Since its launch in 2011, more than 885,000 veterans have joined MVP, making it one of the largest genetics and health programs in the world.
Raghavan explains that studies like this would not be possible without MVP. “MVP is extremely important for these types of studies,” he said. “By linking clinical data with genetic data, we can study clinical outcomes that are not commonly collected in other types of observational cohort data. For example, some of the strongest associations in our study, with peripheral neuropathy, venous insufficiency, osteomyelitis and foot ulcers, would not be routinely collected in many other data including genetics. This link is useful for research and for translating research findings into clinical care.” Beyond the large number of participants, MVP also enables research that was previously impossible due to the participation of veterans from many different groups across the country. “The other important contribution of MVP is its diversity,” Raghavan explained. “While the majority of participants are white, there are large numbers of black and Hispanic participants, who have been underrepresented in genetic studies in the past.” (AND ME)
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