title: A genome-wide association study of northwestern Europeans involves the C-type natriuretic peptide signaling pathway in the etiology of human height variation.
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 (P(combined) = 3.4 x 10(-9)). Notably, a second SNP (rs6718438) located approximately 450 bp away and in strong LD (r(2) = 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 (P(combined) = 2.1 x 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.
authors: Department of Internal Medicine, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors: Karol
authors: K
authors: Estrada
authors: Michael
authors: M
authors: Krawczak
authors: Stefan
authors: S
authors: Schreiber
authors: Kate
authors: K
authors: van Duijn
authors: Lisette
authors: L
authors: Stolk
authors: Joyce B J
authors: JB
authors: van Meurs
authors: Fan
authors: F
authors: Liu
authors: Brenda W J H
authors: BW
authors: Penninx
authors: Jan H
authors: JH
authors: Smit
authors: Nicole
authors: N
authors: Vogelzangs
authors: Jouke Jan
authors: JJ
authors: Hottenga
authors: Gonneke
authors: G
authors: Willemsen
authors: Eco J C
authors: EJ
authors: de Geus
authors: Mattias
authors: M
authors: Lorentzon
authors: Huberta
authors: H
authors: von Eller-Eberstein
authors: Paul
authors: P
authors: Lips
authors: Natascha
authors: N
authors: Schoor
authors: Victor
authors: V
authors: Pop
authors: Jules
authors: J
authors: de Keijzer
authors: Albert
authors: A
authors: Hofman
authors: Yurii S
authors: YS
authors: Aulchenko
authors: Ben A
authors: BA
authors: Oostra
authors: Claes
authors: C
authors: Ohlsson
authors: Dorret I
authors: DI
authors: Boomsma
authors: Andre G
authors: AG
authors: Uitterlinden
authors: Cornelia M
authors: CM
authors: van Duijn
authors: Fernando
authors: F
authors: Rivadeneira
authors: Manfred
authors: M
authors: Kayser
mesh_terms: D001827:Body Height; D005260:Female; D005786:Gene Expression Regulation; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D020098:Natriuretic Peptide, C-Type / Q000235:genetics*; D009426:Netherlands; D020641:Polymorphism, Single Nucleotide; D011498:Protein Precursors / Q000235:genetics*; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics*; D015398:Signal Transduction; D044465:White People / Q000235:genetics*
chemical_list: D011498:Protein Precursors; D020098:Natriuretic Peptide, C-Type; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C