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Genetically predictable height linked to risk of many common health conditions

A large genetic study by the Department of Veterans Affairs’ Millionaire Program (MVP) found that a person’s height may influence their risk of many common health conditions in adulthood. Important findings include an association between height and a lower risk of coronary heart disease, and an association between height and a higher risk of peripheral neuropathy and circulatory disorders.

The results appeared in the June 2, 2022 issue of the Journal Genetics PLOS.

Dr. Sridharan Raghavan of Virginia’s Eastern Colorado Health Care System, who led the study, called the findings “an important contribution to understanding how height relates to clinical conditions from an epidemiological perspective.” Raghavan says more research is needed before the findings lead to changes in clinical care. However, the findings highlight the relationship between height and clinical conditions that affect the lives of veterans, he explains. “The broad scope of our study resulted in a catalog of clinical cases associated with genetically predicted height. In other words, these are conditions in which height may be a risk or protective factor, independent of other environmental conditions that can also influence height and health.”

Height is not usually considered a risk factor for disease. But previous research has shown associations between a person’s height and their likelihood of developing a number of health conditions. What is not well understood is whether this association has a biological basis or is caused by other factors.

The reason a person grows to be an adult is partly due to the genes inherited from their parents. But environmental factors such as nutrition, socioeconomic status, and demographics (for example, age or gender) also play a role in determining final height. This is why it is difficult to determine the relationship between height and disease risk.

To explore this association, VA researchers looked at genetic and medical data from more than 280,000 veterans registered with MVP. They compared this data to a list of 3,290 height-related genetic variants from a recent genome analysis.

They found that risk levels for 127 different medical conditions could be linked to expected height genetically in white patients. Because black patients are underrepresented in genetic studies, less data are available for this population. But in this analysis, medical features associated with height were generally consistent between white and black patients. About 21% of the veterans in the MVP study were black. At least 48 of the links identified in the white patients were also true for the black patients. All of the most significant findings — the association of height with a reduced risk of coronary heart disease and an increased risk of atrial fibrillation, peripheral neuropathy and circulatory disorders — were found in both white and black participants, according to the researchers.

In general, expected height has been genetically linked to a lower and higher risk of disease, depending on the condition. Length appears to protect people from cardiovascular problems. The study linked being taller to a lower risk of developing high blood pressure, high cholesterol and coronary heart disease. But the risk of developing atrial fibrillation was higher in the taller participants. These links have been shown before in the previous search.

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

Peripheral neuropathy is damage to the nerves outside the brain and spinal cord, especially in the extremities. Previous studies have linked length to slowed nerve conduction and nerve problems. The MVP study confirms this association by using genetic tools to indicate an increased risk of nerve problems in tall people.

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

Raghavan described the findings on peripheral neuropathy as “particularly interesting”. He discussed this finding with clinical colleagues who often see patients with peripheral neuropathy. Raghavan’s colleagues confirmed that tall people often showed worse neuropathy, but they were unaware of other studies describing this association.

Conditions such as cellulitis, skin abscesses, chronic leg ulcers, and osteomyelitis have also been linked to higher height. Being tall also appears to increase the risk of circulatory diseases such as varicose veins and thrombosis; blood clots in the veins;

Height may also increase the risk of developing other diseases not related to neuropathy or blood circulation. Toe and toe deformities, conditions that can be caused by being overweight in tall people, were more common in people whose genes predicted they would be tall.

The study also showed that height increases the risk of developing asthma and nonspecific nerve disorders in women, but not in men.

Taken together, the results suggest that height may be an unknown but biologically important and immutable risk factor for many common conditions, particularly those affecting the extremities, according to the researchers. It may be helpful to consider a person’s height when assessing risks and monitoring diseases, they say.

Raghavan says more work is needed before this research can be translated into clinical care. “I think our findings are the first step toward assessing disease risk in that we’re identifying conditions under which altitude may really be a risk factor,” he explains. “Future work will have to assess whether incorporating height into disease risk assessments can guide strategies to modify other risk factors for certain conditions.”

Future work will also focus on potential mechanisms linking altitude to these health conditions.

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

MVP is a national research program to learn how genes, lifestyle, and military exposure affect health and disease. Since its launch in 2011, more than 885,000 veterans have joined the MVP program, making it one of the world’s largest programs in genetics and health.

Raghavan explains that such studies would not be possible without MVP.

MVP is extremely important for these types of studies. By correlating 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, foot ulcers-; It will not be routinely collected in much other data that includes genetics. This association is useful for research and for translating research findings into clinical care.”

Dr. Sridharan Raghavan of VA Eastern Colorado Health Care System

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


Veterans Affairs Research Communications

Journal reference:

Raghavan, S.; et al. (2022) A multi-population large-scale study of the genetically predicted height in the Million Veteran Program. PLOS Genetics.

2022-06-03 00:52:00

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