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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.

SUBMITTER: Estrada K

PROVIDER: S-EPMC2729669 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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A genome-wide association study of northwestern Europeans involves the C-type natriuretic peptide signaling pathway in the etiology of human height variation.

Estrada Karol K Krawczak Michael M Schreiber Stefan S van Duijn Kate K Stolk Lisette L van Meurs Joyce B J JB Liu Fan F Penninx Brenda W J H BW Smit Jan H JH Vogelzangs Nicole N Hottenga Jouke Jan JJ Willemsen Gonneke G de Geus Eco J C EJ Lorentzon Mattias M von Eller-Eberstein Huberta H Lips Paul P Schoor Natascha N Pop Victor V de Keijzer Jules J Hofman Albert A Aulchenko Yurii S YS Oostra Ben A BA Ohlsson Claes C Boomsma Dorret I DI Uitterlinden Andre G AG van Duijn Cornelia M CM Rivadeneira Fernando F Kayser Manfred M

Human molecular genetics 20090701 18

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, t ...[more]

PMID: 19570815

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Project description:IntroductionFluid management in hemodialysis patients is a controversial topic. Brain natriuretic peptide (BNP) is secreted from the heart in response to volume overload, and may be a marker of overhydration in hemodialysis patients. Our aim was to investigate the correlation between BNP and overhydration in a cohort of hemodialysis patients, and to find out whether BNP and overhydration correlate in repeated measurements within individuals with elevated BNP.MethodsThe study was prospective, observational, and had a cross-sectional part and a longitudinal follow-up. The distribution of BNP was investigated in a cohort of 64 hemodialysis patients. Blood samples and bioimpedance spectroscopy measurements were performed before midweek dialysis. Subsequently, 11 study participants with elevated BNP concentrations (>500?pg/mL) were assessed in another nine dialysis sessions each. These individuals also had their cardiac function and heart rate variability (HRV) examined.FindingsBNP was above 500?pg/mL in 38% of the participants, and correlated positively with overhydration (rs =?0.381), inflammation and malnutrition, but not with systolic blood pressure. In comparison to participants with BNP below 500?pg/mL, participants with elevated BNP were older, had lower muscle strength, lower bodyweight and lower levels of hemoglobin and albumin. Echocardiography revealed cardiac anomalies in all 11 participants in the longitudinal follow-up, and HRV, as measured by SDNN, was pathologically low. In repeated measurements, the between-individuals variation of BNP in relation to overhydration was greater (SD?=?0.581) than the within-person variation (SD?=?0.285).DiscussionBNP correlates positively to overhydration, malnutrition, and inflammation. In a subgroup of patients with elevated BNP, who are mainly elderly and frail, BNP reflects individual variation in hydration status, and hence seems to be a modifiable marker of overhydration. These data suggest that BNP is best applied for measuring changes in hydration status within an individual over time.

Dataset Information

A genome-wide association study of northwestern Europeans involves the C-type natriuretic peptide signaling pathway in the etiology of human height variation.

Publications

A genome-wide association study of northwestern Europeans involves the C-type natriuretic peptide signaling pathway in the etiology of human height variation.

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