Large Genetic Study Further Untangles the Height-Health Connection

By Deborah Borfitz

April 2, 2025 | In the largest phenome wide association study across diverse population groups, an international team of researchers have identified 254 statistically significant associations between genetically explained height and various diseases. Genetically predicted height was linked with decreased risk of 90 diseases and increased risk of 164 others, most notably atrial fibrillation, and a series of conditions involving mental health and the endocrine system that have not been previously described. 

Eirini Marouli, Ph.D., associate professor in computational biology at Queen Mary University of London and lead author of the study, says analyzing genetic data across diverse ancestries and incorporating sex-specific analyses identified associations that could help improve early diagnosis and patient care. But it is necessary to understand the causal relationship between adult height and specific disorders, including the ones just reported (npj Genomic Medicine, DOI: 10.1038/s41525-025-00464-w) to advance scientific knowledge of the underlying biology. “This could also lead to lifestyle interventions that help prevent these diseases.”  

Since height is a “highly pleiotropic” trait, it is generally expected to demonstrate associations that span across several disease categories, Marouli says in explaining the strong links found between greater height and conditions related to the circulatory, endocrine/metabolic, and musculoskeletal systems. Physical stature, as defined by a polygenic risk score for height, was associated with hypothyroidism, for example, underscoring the “intricate relationship between growth parameters and thyroid function... [and] the importance of monitoring thyroid health in individuals with growth abnormalities and vice versa.” 

Researchers also observed a connection between height and decreased risk of hyperlipidemia, disorders of lipoid metabolism, and hypertension. “We have shown that taller individuals may have a higher risk of peripheral neuropathy and related complications,” she says. “Studies have found that nerve conduction velocity decreases with increasing height... [and this] may contribute to a greater susceptibility to peripheral neuropathy in taller individuals.” 

Taller stature has moreover been associated with greater risk of conditions such as cellulitis, skin abscesses, chronic leg ulcers, and osteomyelitis, continues Marouli. “These complications are often observed alongside peripheral neuropathy. Interestingly, the association between height and skin and bone infections appears stronger in individuals with diabetes, suggesting that increased height combined with diabetes-related factors may affect infection risk.” 

Overall, being tall appears to be variably good and bad for health. “The availability of larger diverse genetic studies can further facilitate more in-depth analyses of the underlying mediatory pathways of such associations,” says Marouli.  

Sex and Ancestry Breakdown

The analysis found height-health connections both across ancestries and specific to certain ancestries and sexes. In men but not women, for example, increased height was linked to a decreased risk of hyperpotassemia, Marouli reports. 

Additionally, greater height was associated with higher risk of attention deficit hyperactivity disorder and autism—but not when looking solely at females, she says. “In women, increased genetically predicted height was associated with a reduced risk of benign neoplasms in parts of the digestive system; this association was not observed in the sex-combined analysis.” 

The meta-analysis yielded 13 significant associations in women only, with the digestive and neoplasms categories including the most traits, and 126 such associations in men only related primarily to the circulatory system, endocrine/metabolic, and musculoskeletal systems. “Some associations were significant only in men of European ancestry,” Marouli notes. “Specifically, higher genetically predicted height was linked to a decreased risk of anxiety disorders and post-traumatic stress disorder in men.” 

Previous Studies 

The lead up to this latest height-health exploration began with previous work Marouli led as part of the global GIANT (Genetic Investigation of Anthropometric Traits) consortium. That study explored the pleiotropic effects of rare and low-frequency variants on adult height (Nature, DOI: 10.1038/nature21039). 

This was followed by a study looking at potential factors that may be mediating the effect of height on coronary artery disease (Communications Biology, DOI: 10.1038/s42003-019-0361-2). “Our results suggested that this association may be largely attributed to lung function. The availability of larger genetic studies can further facilitate more in-depth analyses of the underlying mediatory pathways of such associations.” 

In yet another study, Marouli and her colleagues performed the largest ever genome-wide association study in the GIANT consortium using the DNA of over five million people from 281 contributing studies (Nature, DOI: 10.1038/s41586-022-05275-y). “We identified 12,111 variants associated with height, which cluster around parts of the genome associated with skeletal growth, and this provided a powerful genetic predictor for height,” she says. 

“The variants identified explain 40% of the variation in height for people of European ancestry, and around 10% to 20% for those of non-European ancestry,” continues Marouli. “This unprecedented scale of the research provided new levels of detail and biological insight as to why people are tall or short, with heritability being linked to various specific genomic regions. The findings showed that genetic variants associated with height are concentrated in regions covering just over 20% of the genome.” 

Clinical Implications

Armed with the results of that meta-analysis, researchers embarked on the latest study to further explore whether genetically predicted height is associated with a series of diseases. “To achieve that we created a genetic score using genetic variants associated with height and explored how this score associates 1,768 traits from over 839,000 people with diverse ancestries,” she says. These included individuals of European, African, East Asian and Hispanic population groups. 

The research underscores the importance of inclusive genetic studies in advancing the “understanding of health across populations and ensuring that scientific progress benefits everyone,” stresses Marouli. The hope is that clinicians can in the future use the learnings to help prevent disease. 

Findings of such studies could potentially help identify individuals who fail to reach their genetically predicted height and aid in the diagnosis of underlying diseases or conditions that may be stunting growth or impacting their overall health, she says. “Continued efforts are essential to improve prediction accuracy across diverse ancestries, accounting more effectively for rare genetic variations and strengthening the link between associated genetic regions and probable causal genes and variants.” 

Population-specific studies “would enable a more precise investigation of height-disease relationships within distinct groups,” adds Marouli. “It is crucial to deepen our understanding of these identified associations at a biological level, distinguishing directly causal relationships from those influenced by other factors.”