This project aims to investigate how genetic variation influences the shape of the proximal femur in modern humans, and how these patterns compare with those observed in Neanderthal skeletal morphology. The missense variant rs288326 in FRZB (sFRP3), a modulator of Wnt signaling involved in skeletal development, is of particular interest. This variant is present in Neanderthal genomes and has been associated in modern humans with altered hip morphology and increased susceptibility to osteoarthritis. Understanding its effects on femoral shape may provide insight into human evolutionary history and musculoskeletal disease risk.
We will use UK Biobank’s large imaging dataset, focusing on abdominal and hip MRI scans, to extract detailed measures of the proximal femur, including femoral head shape, neck length, neck-shaft angle, and overall geometric variation captured through geometric modelling (GM). Participants will be grouped by genotype to compare individuals who carry the FRZB variant with those who do not. To place modern human variation in an evolutionary context, we will compare these genotype-based shape patterns with Neanderthal femoral morphology.
Our objectives are to determine whether rs288326 is associated with systematic changes in proximal femur shape in modern humans, identify whether these shape differences resemble morphological traits typical of Neanderthals, and explore the potential developmental and biomechanical pathways through which Wnt signaling variation influences hip structure. This research will help clarify how introgressed genetic variants from Neanderthals contribute to variation in human skeletal morphology and may inform understanding of hip disease risk in present-day populations.