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- Title
A genome-wide association study of northwestern Europeans involves the C-type natriuretic peptide signaling pathway in the etiology of human height variation.
- Authors
Estrada, Karol; Krawczak, Michael; Schreiber, Stefan; van Duijn, Kate; Stolk, Lisette; van Meurs, Joyce B.J.; Liu, Fan; Penninx, Brenda W.J.H.; Smit, Jan H.; Vogelzangs, Nicole; Hottenga, Jouke Jan; Willemsen, Gonneke; de Geus, Eco J.C.; Lorentzon, Mattias; von Eller-Eberstein, Huberta; Lips, Paul; Schoor, Natascha; Pop, Victor; de Keijzer, Jules; Hofman, Albert
- Abstract
Northwestern Europeans are among the tallest of human populations. The increase in body height in these people appears to have reached a plateau, suggesting the ubiquitous presence of an optimal environment in which genetic factors may have exerted a particularly strong influence on human growth. Therefore, we performed a genome-wide association study (GWAS) of body height using 2.2 million markers in 10 074 individuals from three Dutch and one German population-based cohorts. Upon genotyping, the 12 most significantly height-associated single nucleotide polymorphisms (SNPs) from this GWAS in 6912 additional individuals of Dutch and Swedish origin, a genetic variant (rs6717918) on chromosome 2q37.1 was found to be associated with height at a genome-wide significance level (Pcombined = 3.4 × 10−9). Notably, a second SNP (rs6718438) located ∼450 bp away and in strong LD (r2 = 0.77) with rs6717918 was previously found to be suggestive of a height association in 29 820 individuals of mainly northwestern European ancestry, and the over-expression of a nearby natriuretic peptide precursor type C (NPPC) gene, has been associated with overgrowth and skeletal anomalies. We also found a SNP (rs10472828) located on 5p14 near the natriuretic peptide receptor 3 (NPR3) gene, encoding a receptor of the NPPC ligand, to be associated with body height (Pcombined = 2.1 × 10−7). Taken together, these results suggest that variation in the C-type natriuretic peptide signaling pathway, involving the NPPC and NPR3 genes, plays an important role in determining human body height.
- Publication
Human Molecular Genetics, 2009, Vol 18, Issue 18, p3516
- ISSN
0964-6906
- Publication type
Article
- DOI
10.1093/hmg/ddp296