A new study just published in the journal Science has unveiled groundbreaking findings regarding the genes responsible for shaping and regulating our skeletal structure, as well as shedding light on individuals who are at a higher risk of developing musculoskeletal disorders like osteoarthritis, knee problems, and back pain.

By employing artificial intelligence (AI) to scrutinize a vast array of X-ray images and genetic data, a team of scientists from The University of Texas at Austin and the New York Genome Center has made remarkable progress in identifying the genes responsible for the structure of our skeletons, including aspects like shoulder width to leg length.

The study, which appeared as a featured article in the journal Science, not only unravels mysteries about human evolution but also paves the way for improved prediction of the likelihood of individuals developing ailments like back pain or arthritis in the future.

Humans are the sole large primates with legs longer than arms – a key skeletal variation enabling bipedal movement. The investigators aimed to pinpoint the genetic variations accountable for anatomical changes clearly evident in the fossil record that traces back to the evolution of modern humans.

They were also keen to understand how these skeletal dimensions linked to bipedalism contribute to the prevalence of numerous musculoskeletal diseases, such as knee and hip arthritis — conditions that afflict billions globally and are the foremost reasons for adult disability in the U.S.

The team deployed deep learning algorithms for the automatic quantification of 39,000 medical images to measure the distances between various body parts, like shoulders, knees, and ankles. They compared these measurements with each person’s genetic data and identified 145 genomic locations responsible for dictating skeletal dimensions.

The team further explored the connection between skeletal dimensions and major musculoskeletal diseases.

They discovered that individuals with wider hips relative to their height are more prone to develop osteoarthritis and hip pain. Likewise, people with longer femurs in relation to their height have a higher risk of knee arthritis, knee pain, and other knee-related issues. People with longer torsos compared to their height were more likely to experience back pain.

Eucharist Kun, a biochemistry graduate student at UT Austin and the lead author of the study, noted that “These disorders develop from biomechanical stresses on the joints over a lifetime. Skeletal proportions affect everything from our gait to how we sit, and it makes sense that they are risk factors in these disorders.”

The findings also provide new insights into human evolution. The researchers observed that genetic regions dictating skeletal dimensions coincided more than anticipated with parts of the genome referred to as human accelerated regions – areas that are considerably diverged in humans compared to great apes and many vertebrates. This provides a genetic explanation for the distinctive nature of human skeletal anatomy.

The team’s work also draws parallels with the enduring images of the Renaissance, such as Leonardo Da Vinci’s “The Vitruvian Man”, which encapsulates ratios and lengths of the human form.

Vagheesh Narasimhan, who spearheaded this multi-disciplinary research team. added, “In some ways we’re tackling the same question that Da Vinci wrestled with. What is the basic human form and its proportion? But we are now using modern methods and also asking how those proportions are genetically determined.”

Source: 10.1126/science.adf8009

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