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Genetically predicted height associated with some common health risks


A large genetic study by the US Department of Veterans Affairs Million Veteran Program (MVP) found that a person’s height can affect some of the general health risks of adulthood. Important findings include the association between high and low risk of coronary heart disease, and the association between high and high risk of peripheral neuropathy and cardiovascular disease.

The results were published in the June 2, 2022 issue of the journal. PLOS Genetics..

Dr. Sridalan Ragavan of the VA Eastern Colorado Healthcare System, who led the study, described the results as “an important contribution to understanding how height is related to clinical status from an epidemiological point of view.” .. More research is needed before the findings can lead to changes in clinical care, says Raghavan. However, he explains, the results emphasize the link between height and clinical status, which affects the lives of veterans. “The broad scope of our study has resulted in a catalog of clinical conditions related to genetically predicted height. In other words, these relate to other environmental conditions that may affect height. No, height is a condition that can be a risk factor or a protective factor. Health. “

Height is usually not considered a risk factor for illness. However, past studies have shown that there is a correlation between someone’s height and the likelihood of experiencing many 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 inherited from their parents. However, environmental factors such as nutrition, socioeconomic status, and demographics (such as age and gender) also play a role in determining final height. This is why it can be difficult to determine the relationship between height and risk of illness.

To investigate this relationship, VA researchers looked at genetic and medical data from more than 280,000 veterans enrolled in the MVP. They compared these data with a list of 3,290 height-related gene mutations from recent genomic analyzes.

They found that the risk levels of 127 different medical conditions may be associated with the genetically predicted height of Caucasian patients. Black patients are less represented in genetic studies, so less data is available in this population. However, in this analysis, height-related medical features were largely consistent between 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 applied to black patients. All of the most important findings, according to the researchers-; height is associated with a reduced risk of coronary heart disease and an increased risk of atrial fibrillation, peripheral neuropathy, and circulatory disorders-; with blacks Found in both white participants.

Overall, genetically predicted height was associated with both lower and higher risk of illness, depending on the condition. Being tall seems to protect people from cardiovascular problems. This study associated tallness with a low risk of high blood pressure, high cholesterol, and coronary heart disease. However, the risk of atrial fibrillation was higher in taller participants. These connections have been shown in previous studies.

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 cardiovascular disease, including veins.

Peripheral neuropathy is damage to the nerves outside the brain and spinal cord, especially in the limbs. Previous studies have associated height with delayed nerve conduction and nerve problems. MVP studies confirm this link using genetic tools that suggest an increased risk of neuropathy in tall people.

Researchers have associated genetically predicted heights with conditions such as erectile dysfunction and urinary retention. Both of these are associated with neuropathy.

Raghavan called the findings on peripheral neuropathy “especially interesting.” He discussed this finding with a clinical colleague who often sees patients with peripheral neuropathy. Raghavan’s colleagues confirmed that tall people often show the worst neuropathy, but they were unaware of other studies explaining this link.

Symptoms such as cellulitis, skin abscess, chronic leg ulcer, and osteomyelitis were also associated with height. Being tall also seems to increase the risk of cardiovascular diseases such as varicose veins and thrombosis-; intravenous thrombosis.

Height can also increase the risk of neuropathy and other conditions not associated with circulation. Toe and foot deformities are conditions that can be caused by weight gain in tall people and are common in people genetically predicted to be tall.

The study also showed that height increases the risk of asthma and nonspecific neuropathy in women rather than men.

In summary, according to researchers, the results may be an invariant risk factor for some common conditions, especially those that affect the limbs, although height is not recognized but biologically important. It suggests that there is sex. They say that it may be useful to consider a person’s height when assessing risk and illness monitoring.

More work is needed before converting this study into clinical care, says Raghavan. “I think our findings are the first step towards a disease risk assessment in identifying conditions where height can really be a risk factor,” he explains. “In future work, we need to assess whether height can be incorporated into the disease risk assessment to inform strategies for modifying other risk factors for a particular condition.”

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

Researchers from several VA Healthcare Centers participated in this study. This includes, but is not limited to, Dr. Tim Asimes of the VA Palo Alto Healthcare System. Dr. Yangsan of the Atlanta VA Medical Center. Dr. Chris O’Donnell, one of the national leaders of MVP, previously belonged to the VA Boston Healthcare System and is now a member of Novartis.

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

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

MVP is very important for these types of studies. By linking clinical data with genetic data, it is possible to study clinical outcomes that are not commonly collected by other types of observational cohort data. For example, some of the stronger associations in our study-; peripheral neuropathy, venous insufficiency, osteomyelitis, foot ulcers and-; many other data, including genetics, are not collected on a regular basis. This collaboration will help bring research and findings back to clinical care. “

Dr. Sridalan Raggavan of VA Eastern Colorado Healthcare System

Not only is the MVP very large in number of participants, but it also enables previously impossible investigations due to the participation of various groups of veterans across the country. “Another important contribution of MVP is its diversity,” Raghavan explained. “The majority of participants are Caucasian, but there are many black and Hispanic participants who have been underestimated in genetic studies in the past.”


Journal reference:

Raghavan, S., et al. (2022) A related study of the entire multipopulation phenome of genetically predicted height in the Million Veteran Program. PLOS genetics.




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