As much as 90 percent of variation in adult height may be caused by genetic inheritance, but a multitude of genes are involved. Most of these have yet to be discovered.
Now a new meta-analysis of data from more than 100,000 people has identified variants in over two dozen genes that were not previously associated with height. The study also confirmed genetic associations in more than 30 previously known height genes. "Although the discoveries may not have immediate clinical use, the approach we used will undoubtedly be helpful in discovering genes that influence other traits and diseases," said the co-study leader, Hakon Hakonarson, M.D., Ph.D., director of the Center for Applied Genomics at The Children's Hospital of Philadelphia.
Using an existing gene chip customized to include approximately 50,000 SNPs (single-base changes in one letter of DNA's genetic code) in genes having a high likelihood of association with cardiovascular disease, the study team searched variants for SNPs linked to adult height. This study, said Hakonarson, which used height as a lead phenotype for a gene-rich SNP chip enhanced in rare variant coverage, suggests that such platforms will succeed in identifying genetic variants that contribute to multiple other cardiovascular diseases, and potentially to other complex traits.
"This is a proof-of-concept that more dense genotyping of selected gene-rich datasets allows us to find additional genes that have gone undetected in studies using conventional SNP arrays," said Hakonarson. Hakonarson and co-study leader Brendan J. Keating, D.Phil., also from the Center for Applied Genomics, led the large, international collaborative group whose study appeared online Dec. 30 in the American Journal of Human Genetics.
Many of the variants are in locations with interesting functional rolesin energy metabolism, growth hormones, circadian rhythm and cellular growthof possible relevance to the biology of gro
|Contact: John Ascenzi|
Children's Hospital of Philadelphia