When it comes to height, our fate is sealed along with our growth plates: cartilage near the ends of bones that hardens as a child develops. Publication of the research on April 14 in the journal Cellular Genomics shows that the cells in these plates determine the length and shape of our bones and may hint at our height. The study identified potential “height genes” and found that genetic changes that affect cartilage cell maturation can strongly influence adult height.
“The study really understands skeletal genetics,” says lead author Nora Renthal, of Children’s Hospital Boston and Harvard University. As a pediatric endocrinologist who cares for children with skeletal diseases, she is interested in understanding how bones grow. “Height is a good starting point for understanding the relationship between genes, growth plates, and skeletal growth because we can measure the height of every human being.”
To identify genes associated with height, the team analyzed 600 million mouse cartilage cells to identify genes that, when knocked out, can alter cell growth and maturation. These types of cellular changes in the growth plate are known to lead to variations in human height. The search yielded 145 genes, mostly related to skeletal disorders and crucial for growth plate maturation and bone formation.
The team then compared the discovered genes with data from genome-wide association studies (GWAS) of human height. GWAS allows researchers to examine the entire human genome to identify critical points where “height genes” are found in our DNA. But these regions can contain multiple genes, making it difficult for researchers to track down and study an individual target.
“It’s like looking at a friend’s house, but you only know the zip code,” Renthal says. “It’s hard.”
The comparison revealed that genes affecting cartilage cells overlap with GWAS human height hotspots, locating precisely the genes in our DNA that likely play a role in determining our height. Renthal and his team also discovered that many of the height genes suggested by GWAS lead to early maturation in cartilage cells. These findings suggest that genetic changes that affect cartilage cell maturation may further influence height.
Renthal notes that studies in mouse cells may not fully translate to humans, and GWAS are observational studies that cannot fully illustrate the cause and effects of altitude. But her study provides a novel method to bridge the two methods and provide new insights into human genetics.
Next, the team plans to use the method to understand the effect of hormones on cartilage cells. They will also investigate some of the 145 genes that have no known connection to skeletal growth. The research may reveal new genes and pathways that play a role in bone.
“I see patients with skeletal dysplasia, where there is no treatment because genetics caused their bones to grow this way,” Renthal says. “I hope that the more we can understand about the biology of the growth plate, the more we will be able to intervene earlier in the growing skeletons and life of a child.”