Journal article

Defining the role of common variation in the genomic and biological architecture of adult human height

Wood, Andrew R.; Esko, Tonu; Yang, Jian; Vedantam, Sailaja; Pers, Tune H.; Gustafsson, Stefan; Chun, Audrey Y.; Estrada, Karol; Luan, Jian'An; Kutalik, Zoltan

Elect Med Records & Genom eMERGE C; MIGen Consortium; PAGE Consortium; LifeLines Cohort Study

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 similar to 2,000, similar to 3,700 and similar to 9,500 SNPs explained similar to 21%, similar to 24% and similar to 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/beta-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.


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