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Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

Original publication

DOI

10.1038/ng.3097

Type

Journal article

Journal

Nature genetics

Publication Date

11/2014

Volume

46

Pages

1173 - 1186

Addresses

Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.

Keywords

Electronic Medical Records and Genomics (eMEMERGEGE) Consortium, MIGen Consortium, PAGEGE Consortium, LifeLines Cohort Study, Humans, Body Height, Oligonucleotide Array Sequence Analysis, Analysis of Variance, Genetics, Population, Polymorphism, Single Nucleotide, Adult, European Continental Ancestry Group, Genetic Variation, Genome-Wide Association Study