Many skeletal changes occurred on the path to modern humans, leading to bipedalism and susceptibility to musculoskeletal diseases. However, the genetic basis of skeletal proportions (SP) remains to be better characterized.
Researchers at the University of Texas at Austin and the New York Genome Center used artificial intelligence to evaluate tens of thousands of X-ray images and genetic sequences to identify the genes that shape our skeletons, from the width of our shoulders to the length of our legs.
The study is a powerful demonstration of AI’s impact on medicine, especially when it comes to analyzing and quantifying imaging data, as well as integrating this information with health records and genetics at a faster and larger scale.
The researchers set out to identify which genetic variations are responsible for the physical changes seen in the fossil record leading to modern humans, from Australopithecus to Neanderthals. In addition, they were interested in how the skeletal proportions that allow bipedalism affect the risk of developing various musculoskeletal disorders, such as knee and hip arthritis, which affect billions of people worldwide and are the leading cause of disability in adults in the United States.
Using deep learning algorithms, researchers automatically calculated distances between shoulders, knees, ankles and other body points in 39,000 medical photographs. By comparing these measurements to each individual’s genetic makeup, they found 145 sites in the genome that control skeletal proportions.
said Tarjinder (TJ) Singh, co-author of the study, associate member of NYGC and assistant professor in the Columbia University Department of Psychiatry. “Our work provides a road map linking specific genes to skeletal length in different parts of the body, allowing developmental biologists to investigate this systematically.”
The scientists also looked at how skeletal proportions were related to major musculoskeletal diseases, and found that those with larger hip width-to-height ratios were more likely to experience hip discomfort and osteoarthritis. Similarly, those with a larger femur (femur) length-to-height ratio are more likely to develop knee problems such as arthritis and discomfort. Back pain is more common in people with a large trunk length-height ratio.
said Eucharist Kuhn, a UT Austin biochemistry graduate student and lead author on the paper. “These disorders develop from the biomechanical stresses placed on the joints throughout life. Skeletal proportions affect everything from the way we walk to the way we sit, meaning they are risk factors for these disorders.
Their research findings also have implications for how we understand evolution. The scientists found that some genetic regions that affect skeletal proportions overlap with parts of the genome known as human accelerated regions. These parts of the human genome have undergone significant divergence from those shared by great apes and other vertebrates. It explains how human skeletal morphology has changed over time in relation to genomics.
- Eucharist Kuhn, Emily Javan, et al. Genetic architecture and evolution of the human skeleton. science DOI: 10.1126/science.adf8009