Vulnerability to osteoarthritis from antagonistic pleiotropy at loci that induce short stature to protect against freezing?

Capellini, T. D., Chen, H., Cao, J., Doxey, A. C., Kiapour, A. M., Schoor, M., & Kingsley, D. M. (2017). Ancient selection for derived alleles at a GDF5 enhancer influencing human growth and osteoarthritis risk. Nature Genetics. (only a preview, article is behind a paywall, but a preprint is available here.)

A noncoding single base pair polymorphism adjacent to GDF5 that causes shorter stature is more prevalent in northern Europe and Asia, and there are signals of selection in the region. The authors say, in a nice overview in Science Daily, “”We argue that shorter height may have been advantageous in the past…because if you were living in a colder climate, having a short, stocky body may actually help you survive,” he said. “When you look at animals that reside in the arctic, they tend to have shorter appendages to reduce the risk of frostbite and to maintain body heat. Interestingly, having the short height variant in this region is thus linked to having an increased risk of knee and hip osteoarthritis, because of separate mutations.”  They also note, “a shorter femoral neck might also have been a protective mechanism that’s brought this sequence to very high frequency in some populations.”

If confirmed, this will be a classic example of a trait that gives both advantages and disadvantages in certain geographical locations, a classic example of antagonistic pleiotropy.

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