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Hundreds of variants clustered in genomic loci and biological pathways affect human height |
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| Authors: | Lango Allen Hana Estrada Karol Lettre Guillaume Berndt Sonja I Weedon Michael N Rivadeneira Fernando Willer Cristen J Jackson Anne U Vedantam Sailaja Raychaudhuri Soumya Ferreira Teresa Wood Andrew R Weyant Robert J Segrè Ayellet V Speliotes Elizabeth K Wheeler Eleanor Soranzo Nicole Park Ju-Hyun Yang Jian Gudbjartsson Daniel Heard-Costa Nancy L Randall Joshua C Qi Lu Vernon Smith Albert Mägi Reedik Pastinen Tomi Liang Liming Heid Iris M Luan Jian'an Thorleifsson Gudmar Winkler Thomas W Goddard Michael E Sin Lo Ken Palmer Cameron Workalemahu Tsegaselassie Aulchenko Yurii S Johansson Asa |
| Affiliation: | Genetics of Complex Traits, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter EX1 2LU, UK. |
| Abstract: | Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P? |
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