Genetically predicted height linked to risk for several common health conditions

A large genetic study by the US Department of Veteran Affairs’ Million Veterans Program (MVP) has found that a person’s height can affect their risk for a number of common health conditions in adulthood. Important findings include a link between height and a lower risk of coronary heart disease, and a link between height and higher risk for peripheral neuropathy and circulatory disorders.

The results were published in the June 2, 2022 issue of the journal plus genetics,

Dr. Sreedharan Raghavan of the VA Eastern Colorado Health Care System, who led the study, described the results as a “significant contribution to the understanding of height related to clinical conditions from an epidemiological perspective.” More research is needed before the findings could lead to a change in clinical care, says Raghavan. However, the results highlight an association between height and clinical conditions that affect the lives of veterans, he explains. “The broad scope of our study yielded a list of clinical conditions associated with genetically inferred height. In other words, these are conditions for which height may be a risk factor or a protective factor, notwithstanding other environmental conditions that may be associated with height.” can also affect height and health.”

Height is not generally considered a risk factor for diseases. But previous research has shown that there are links between how tall a person is and their likelihood of experiencing several health conditions. What is not well understood is whether this correlation has a biological basis or is due to other factors.

How tall someone is as an adult is partly due to the genes they inherit from their parents. But environmental factors such as nutrition, socioeconomic status and demographics (for example, age or gender) also play a role in determining ultimate height. This is why the relationship between altitude and disease risk can be difficult to determine.

To explore this relationship, 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 height from a recent genome analysis.

They found that risk levels of 127 different medical conditions could be linked to genetically predicted height in white patients. Because black patients are under-represented in genetic studies, little data are available on this population. But in this analysis, medical symptoms associated with height were generally consistent across black and white patients. About 21% of the Veterans in the MVP study were Black. At least 48 links identified in White patients also held true for Black patients. According to the researchers, all the most important findings-; Being associated with 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.

Overall, genetically predicted height was associated with both low and high disease risk, depending on the condition. Being tall appears to protect people from cardiovascular problems. Studies have linked high blood pressure, high cholesterol and a lower risk of coronary heart disease. But the risk of atrial fibrillation was higher in the taller participants. These connections have been shown previously in previous research.

Conversely, being tall may increase the risk of most of the non-cardiovascular conditions considered in the study. This was especially true for peripheral neuropathy and circulatory disorders involving nerves.

Peripheral neuropathy is damage to the nerves outside the brain and spinal cord, especially in the limbs. Earlier studies have linked height with slow nerve conduction and nerve problems. The MVP study confirms this link by using genetic tools to suggest a higher risk of nerve problems in tall people.

Researchers linked genetically predicted height to conditions such as erectile dysfunction and urinary retention, both of which are associated with neuropathy.

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 relationship.

Conditions such as cellulitis, skin abscesses, chronic leg ulcers and osteomyelitis were also linked to elevation. Being tall also increases the risk of circulatory conditions like varicose veins and thrombosis – blood clots in the veins.

Elevation can also increase the risk of other conditions not associated with neuropathy or circulation. Toe and foot deformities, conditions caused by increased weight in tall people, were more common in people whose genetics predicted they would be tall.

The study also showed that height increased the risk of asthma and non-specific nervous disorders in women, but not in men.

Taken together, the results suggest that height may be an unrecognized but biologically important and irreversible risk factor for many common conditions, particularly those that affect the extremities, according to the researchers. They say it may be useful to consider a person’s height when assessing risk and disease surveillance.

More work is needed before this research can be translated into clinical care, says Raghavan. “I think our findings are a first step towards disease risk assessment, in which we identify conditions for which altitude may actually be a risk factor,” he tells WebMD. “Future work will have to evaluate whether the inclusion of height in disease risk assessments can inform strategies for modifying other risk factors for specific conditions.”

Future work will also focus on the possible mechanisms that link these health conditions to height.

Researchers from several VA health care centers participated in the study, including, but not limited to, Dr. Tim Asims of the VA Palo Alto Health Care System; Dr. Yan Sun from Atlanta VA Medical Center; and Dr. Chris O’Donnell, one of the MVP’s national leaders, first with VA Boston Healthcare System and now with Novartis.

The MVP is a national research program to explore 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 world’s largest programs on genetics and health.

Raghavan points out that without MVP this kind of education would not be possible.

MVP is extremely important for this type of study. By combining clinical data with genetic data, we can study clinical outcomes that are not typically collected in other types of observational cohort data. For example, some strong associations—with peripheral neuropathy, venous insufficiency, osteomyelitis, leg ulcers—in our study; In many other data, including genetics, would not be routinely collected. This engagement is helpful for research and for translating research findings back into clinical care.”


Dr. Sreedharan Raghavan from VA Eastern Colorado Health Care System

In addition to its vast number of participants, MVP allows research previously impossible due to the participation of veterans from many different groups across the country. “Another important contribution of MVP is its diversity,” explained Raghavan. “While the majority of participants are white, there are a large number of black and Hispanic participants, who have been underrepresented in genetic studies in the past.”

Source:

Journal Reference:

Raghavan, S., and others. (2022) A multi-population phenome-wide association study of genetically predicted height in the Million Veterans Program. PLOS Genetics. doi.org/10.1371/journal.pgen.1010193,

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