Genome-wide association analysis identifies 20 loci that influence adult height.
Weedon MN., Lango H., Lindgren CM., Wallace C., Evans DM., Mangino M., Freathy RM., Perry JRB., Stevens S., Hall AS., Samani NJ., Shields B., Prokopenko I., Farrall M., Dominiczak A., Diabetes Genetics Initiative None., Wellcome Trust Case Control Consortium None., Johnson T., Bergmann S., Beckmann JS., Vollenweider P., Waterworth DM., Mooser V., Palmer CNA., Morris AD., Ouwehand WH., Cambridge GEM Consortium None., Zhao JH., Li S., Loos RJF., Barroso I., Deloukas P., Sandhu MS., Wheeler E., Soranzo N., Inouye M., Wareham NJ., Caulfield M., Munroe PB., Hattersley AT., McCarthy MI., Frayling TM.
Adult height is a model polygenic trait, but there has been limited success in identifying the genes underlying its normal variation. To identify genetic variants influencing adult human height, we used genome-wide association data from 13,665 individuals and genotyped 39 variants in an additional 16,482 samples. We identified 20 variants associated with adult height (P < 5 x 10(-7), with 10 reaching P < 1 x 10(-10)). Combined, the 20 SNPs explain approximately 3% of height variation, with a approximately 5 cm difference between the 6.2% of people with 17 or fewer 'tall' alleles compared to the 5.5% with 27 or more 'tall' alleles. The loci we identified implicate genes in Hedgehog signaling (IHH, HHIP, PTCH1), extracellular matrix (EFEMP1, ADAMTSL3, ACAN) and cancer (CDK6, HMGA2, DLEU7) pathways, and provide new insights into human growth and developmental processes. Finally, our results provide insights into the genetic architecture of a classic quantitative trait.