Over 80 rare or low-frequency genetic variants have been found to associate with human height, finds research published online in Nature this week. Despite the low frequency of these genetic variants, the genes identified have a considerable effect on human height and provide insights into the genetic factors that determine how tall we are.
Much of what determines our height is inherited. Although approximately 700 common genetic variants have been associated with differences in height, the role of rare and low-frequency variants is less well understood. The analysis of over 700,000 individuals identifies new genetic variants associated with height, including 83 candidate genes that have rare or low-frequency variants, report Guillaume Lettre, Panos Deloukas, Joel Hirschhorn and colleagues. Some of these genes are found to account for a difference in height of around two centimetres in carriers compared to non-carriers. Many of the variants have been identified in genes previously implicated in growth disorders, but the study also highlights new gene candidates and biological pathways involved in growth.
The common genetic variants associated with height identified prior to this research only account for around 20% of its heritability. This study demonstrates that rare and low-frequency gene variants also have an important role in height, accounting for a further 1.7% of heritability. This finding may also have implications for understanding the genetic architecture of other complex human traits and may provide new tools for predicting disease risks and developing treatments.