Identification of ten loci associated with height highlights new biological pathways in human growth |
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Authors: | Lettre Guillaume,Jackson Anne U,Gieger Christian,Schumacher Fredrick R,Berndt Sonja I,Sanna Serena,Eyheramendy Susana,Voight Benjamin F,Butler Johannah L,Guiducci Candace,Illig Thomas,Hackett Rachel,Heid Iris M,Jacobs Kevin B,Lyssenko Valeriya,Uda Manuela Diabetes Genetics Initiative FUSION KORA Prostate, Lung Colorectal Ovarian Cancer Screening Trial Nurses' Health Study SardiNIA,Boehnke Michael,Chanock Stephen J,Groop Leif C,Hu Frank B,Isomaa Bo,Kraft Peter,Peltonen Leena,Salomaa Veikko,Schlessinger David,Hunter David J,Hayes Richard B,Abecasis Gonçalo R,Wichmann H-Erich,Mohlke Karen L |
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Affiliation: | Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA. |
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Abstract: | Height is a classic polygenic trait, reflecting the combined influence of multiple as-yet-undiscovered genetic factors. We carried out a meta-analysis of genome-wide association study data of height from 15,821 individuals at 2.2 million SNPs, and followed up the strongest findings in >10,000 subjects. Ten newly identified and two previously reported loci were strongly associated with variation in height (P values from 4 x 10(-7) to 8 x 10(-22)). Together, these 12 loci account for approximately 2% of the population variation in height. Individuals with < or =8 height-increasing alleles and > or =16 height-increasing alleles differ in height by approximately 3.5 cm. The newly identified loci, along with several additional loci with strongly suggestive associations, encompass both strong biological candidates and unexpected genes, and highlight several pathways (let-7 targets, chromatin remodeling proteins and Hedgehog signaling) as important regulators of human stature. These results expand the picture of the biological regulation of human height and of the genetic architecture of this classical complex trait. |
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