From height to health: largest global genetic study reveals hidden risks and benefits linked to stature

The research, published in NPJ Genomic Medicine, used data from six cohorts of diverse ancestries, including European, African, East Asian, and Hispanic populations, to explore the links between genetically predicted height and various diseases. Applying a Phenome-Wide Association Study (PheWAS) method, the international team of researchers, led by Queen Mary University of London, analysed each group both within and across different ancestries. PheWAS is a method that examines how a genetic score – in this case for height –is associated with a broad range of health conditions. Rather than focusing on a single disease, it scans numerous health outcomes to uncover unexpected connections between the genetically predicted trait and various diseases. 

The researchers looked at 1,768 traits from over 800,000 people with diverse ancestries and found 254 statistically significant associations between genetically predicted height and disease across ancestries. The strongest links seen were between greater height and conditions related to the circulatory system, the endocrine/metabolic system, and musculoskeletal categories. 

More specifically, the strongest association was observed between genetically predicted height and atrial fibrillation in the sex-combined across ancestries analysis. The study also revealed ancestry-specific and sex-specific associations. For example, increased genetically predicted height was associated with decreased risk of Hyperpotassemia in males but showed no association in females. 

Some signals were significant only in the European ancestry meta-analysis for males ​and not in the cross-ancestry meta-analysis. For instance, increased genetically predicted height was associated with a decreased risk of anxiety disorders and post-traumatic stress disorder in males. One significant association was identified in the female-only meta-PheWAS but was not observed in the sex-combined meta-PheWAS: benign neoplasm of other parts of the digestive system. 

Dr Areti Papadopoulou, Postdoctoral Research Associate at the Medical Research Council Biostatistics Unit and first author, said: "Our study explored disease related outcomes in up to 840,000 individuals of European, African, East Asian and Hispanic population groups with genetically predicted height. We report associations with a series of disorders, involving mental disorders and the endocrine system, that have not been previously associated with genetically 
predicted height." 

Dr Eirini Marouli, last author and Associate Professor in Computational Biology in the Faculty of Medicine and Dentistry, said: “Our study reveals significant links between genetically predicted height and various health conditions, providing new perspectives on disease risk. As a complex trait, height's associations with disease offer valuable insights into underlying biological mechanisms.  By analysing genetic data across diverse ancestries and incorporating sex-specific analyses, we have identified associations that could improve early diagnosis and patient care. This research underscores the importance of inclusive genetic studies, advancing our understanding of health across populations and ensuring that scientific progress benefits everyone."