According to a significant genetic study, a person’s height may have an impact on their chance of developing a number of prevalent illnesses as adults. Significant results include a relationship between height and increased risk for peripheral neuropathy and circulatory problems as well as a relationship 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 from the VA Eastern Colorado Health Care System, who led the study, described the results as “a significant contribution to understanding how height is related to clinical conditions from an epidemiologic perspective.” More research is needed before the findings might lead to changes in clinical care, says Raghavan. However, the results highlight the association between height and clinical conditions that impact the lives of Veterans, he explains. “The broad scope of our study yielded a catalogue 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, irrespective of other environmental conditions that also could impact height and health.” Height is not often regarded as a disease risk factor. However, prior studies have found associations between a person’s height and their propensity to develop a number of health issues. Whether this link has a biological foundation or is caused by other factors is not fully understood.
Part of a person’s adult height is determined by genes they got from their parents. However, environmental aspects like diet, socioeconomic standing, and demographics (such as age or gender) also have an impact on final height. This is why finding a link between height and the risk of contracting a disease can be challenging. To explore this connection, VA researchers looked at genetic and medical data from more than 280,000 Veterans enrolled in MVP. They compared these data to a list of 3,290 genetic variants associated with a height from a recent genome analysis.
They found that risk levels of 127 different medical conditions can be linked to genetically predicted height in white patients. Since Black patients are less well-represented in genetic studies, fewer data are available on this population. But in this analysis, the medical traits associated with height were generally consistent across Black and white patients. About 21% of Veterans in the MVP study were Black. At least 48 of the links identified in white patients also held true for Black patients. All of the most significant findings — height is linked to a lower risk of coronary heart disease and a higher risk of atrial fibrillation, peripheral neuropathy, and circulatory disorders — were found in both 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 appears to protect people from cardiovascular problems. The study linked being taller to a lower risk of high blood pressure, high cholesterol, and coronary heart disease. But the risk of atrial fibrillation was higher in taller participants. These connections have been shown before in previous research.
On the other hand, the majority of non-cardiovascular illnesses taken into account in the study may be more likely among those who are tall. This was notably true for circulation conditions that affected the veins and peripheral neuropathy. Damage to the nerves outside the brain and spinal cord, notably in the limbs, is known as peripheral neuropathy. Height has been associated with poorer neural conduction and nerve issues in earlier research. Using genetic tools to suggest a higher risk of nerve issues in tall people, the MVP study validates this connection.
The researchers established a connection between genetically predicted height and ailments like 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 weren’t aware of other studies describing this association.
Conditions such as cellulitis, skin abscesses, chronic leg ulcers, and osteomyelitis were linked to height as well. Being tall also appears to raise the risk of circulatory conditions such as varicose veins and thrombosis — blood clots in veins. Height also may increase the risk of other conditions not connected to neuropathy or circulation. Toe and foot deformities, conditions that could be caused by increased weight bearing of tall people, were more common in people whose genetics predicted they would be tall.
The study also showed height increases the risk of asthma and non-specific nerve disorders in women but not men. Taken together, the results suggest that height may be an unrecognized but biologically important and unchangeable risk factor for several common conditions, particularly those that affect the extremities, according to the researchers. It may be useful 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, says Raghavan. “I think our findings are the first step toward disease risk assessment in that we identify conditions for which height might truly be a risk factor,” he explains. “Future work will have to evaluate whether incorporating height into disease risk assessments can inform strategies to modify other risk factors for specific conditions.” Future work will also focus on the potential mechanisms that tie height to these health conditions.
Researchers from multiple VA health care centres participated in the study, including, but not limited to, Dr Tim Assimes from VA Palo Alto Health Care System; Dr Yan Sun from the Atlanta VA Medical Center; and Dr Chris O’Donnell, one of the national leaders of MVP, previously with the 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 illness. Since launching in 2011, over 8,85,000 Veterans have joined MVP, making it one of the world’s largest programs on genetics and health.
Raghavan explains that studies such as 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 stronger associations in our study — with peripheral neuropathy, venous insufficiency, osteomyelitis, and foot ulcers — would not be collected routinely in lots of other data that include genetics. This linkage is helpful for research and for translating research findings back to clinical care.” Beyond its sheer number of participants, MVP also allows for previously impossible research because of the participation of Veterans from many different groups across the nation. “The other important contribution of MVP is its diversity,” explained Raghavan. “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.”