Defining the role of common variation in the genomic and biological architecture of adult human height
- PMID: 25282103
- PMCID: PMC4250049
- DOI: 10.1038/ng.3097
Defining the role of common variation in the genomic and biological architecture of adult human height
Abstract
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.
Figures



References
-
- Fisher RA. The correlation between relatives on the supposition of Mendelian inheritance. Trans R Soc. 1918;52:399–433.
-
- Silventoinen K, et al. Heritability of adult body height: a comparative study of twin cohorts in eight countries. Twin Res. 2003;6:399–408. - PubMed
Publication types
MeSH terms
Grants and funding
- G0500070/MRC_/Medical Research Council/United Kingdom
- T32 GM080178/GM/NIGMS NIH HHS/United States
- P30 CA015704/CA/NCI NIH HHS/United States
- R01 DK072193/DK/NIDDK NIH HHS/United States
- MR/L003120/1/MRC_/Medical Research Council/United Kingdom
- P30 GM103341/GM/NIGMS NIH HHS/United States
- RG/10/12/28456/BHF_/British Heart Foundation/United Kingdom
- R01 DK093757/DK/NIDDK NIH HHS/United States
- SP/08/002/24118/BHF_/British Heart Foundation/United Kingdom
- CZB/4/710/CSO_/Chief Scientist Office/United Kingdom
- CZB/4/672/CSO_/Chief Scientist Office/United Kingdom
- RP-PG-0310-1002/DH_/Department of Health/United Kingdom
- G0601463/MRC_/Medical Research Council/United Kingdom
- U01 HG007419/HG/NHGRI NIH HHS/United States
- RG/08/008/25291/BHF_/British Heart Foundation/United Kingdom
- R01 HL109946/HL/NHLBI NIH HHS/United States
- FS/11/35/28871/BHF_/British Heart Foundation/United Kingdom
- MC_UP_A100_1003/MRC_/Medical Research Council/United Kingdom
- P01 GM099568/GM/NIGMS NIH HHS/United States
- 085301/WT_/Wellcome Trust/United Kingdom
- RG/08/014/24067/BHF_/British Heart Foundation/United Kingdom
- FS/12/33/29561/BHF_/British Heart Foundation/United Kingdom
- MC_UU_12019/1/MRC_/Medical Research Council/United Kingdom
- U01 CA164930/CA/NCI NIH HHS/United States
- R01 DK075787/DK/NIDDK NIH HHS/United States
- UL1 TR000124/TR/NCATS NIH HHS/United States
- MC_UU_12015/1/MRC_/Medical Research Council/United Kingdom
- PG/07/085/23349/BHF_/British Heart Foundation/United Kingdom
- MC_U106179471/MRC_/Medical Research Council/United Kingdom
- R25 GM062459/GM/NIGMS NIH HHS/United States
- P30 DK063491/DK/NIDDK NIH HHS/United States
- P30 HD018655/HD/NICHD NIH HHS/United States
- FS/14/12/30540/BHF_/British Heart Foundation/United Kingdom
- MC_UU_12015/2/MRC_/Medical Research Council/United Kingdom
- FS/12/8/29377/BHF_/British Heart Foundation/United Kingdom
- P30 DK072488/DK/NIDDK NIH HHS/United States
- MC_U106179472/MRC_/Medical Research Council/United Kingdom
- G1002084/MRC_/Medical Research Council/United Kingdom
- 090532/WT_/Wellcome Trust/United Kingdom
- MC_PC_U127561128/MRC_/Medical Research Council/United Kingdom
- RG/09/012/28096/BHF_/British Heart Foundation/United Kingdom
- 098395/WT_/Wellcome Trust/United Kingdom
- U01 DK062370/DK/NIDDK NIH HHS/United States
- R01 HL088215/HL/NHLBI NIH HHS/United States
- R01 GM075091/GM/NIGMS NIH HHS/United States
- MR/K006584/1/MRC_/Medical Research Council/United Kingdom
- MR/K013351/1/MRC_/Medical Research Council/United Kingdom
- MC_UU_12015/5/MRC_/Medical Research Council/United Kingdom
- 323195/ERC_/European Research Council/International
- R01 HL117626/HL/NHLBI NIH HHS/United States
- 098381/WT_/Wellcome Trust/United Kingdom
- R01 HL117078/HL/NHLBI NIH HHS/United States
- T32 HL007055/HL/NHLBI NIH HHS/United States
- R01 HL087700/HL/NHLBI NIH HHS/United States
- P30 CA071789/CA/NCI NIH HHS/United States
- MR/L01629X/1/MRC_/Medical Research Council/United Kingdom
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous