Molecular prediction of disease risk and severity in a large Dutch Crohn's disease cohort

Item does not contain fulltextBACKGROUND: Crohn's disease and ulcerative colitis have a complex genetic background. We assessed the risk for both the development and severity of the disease by combining information from genetic variants associated with inflammatory bowel disease (IBD). METHODS: We studied 2804 patients (1684 with Crohn's disease and 1120 with ulcerative colitis) and 1350 controls from seven university hospitals. Details of the phenotype were available for 1600 patients with Crohn's disease and for 800 with ulcerative colitis. Genetic association for disease susceptibility was tested for the nucleotide-binding and oligomerisation domain 2 gene (NOD2), the IBD5 locus, the Drosophila discs large homologue 5 and autophagy-related 16-like 1 genes (DLG5 and ATG16L1) and the interleukin 23 receptor gene (IL23R). Interaction analysis was performed for Crohn's disease using the most associated single nucleotide polymorphism (SNP) for each locus. Odds ratios were calculated in an ordinal regression analysis with the number of risk alleles as an independent variable to analyse disease development and severity. RESULTS: Association with Crohn's disease was confirmed for NOD2, IBD5, DLG5, ATG16L1 and IL23R. Patients with Crohn's disease carry more risk alleles than controls (p = 3.85 x 10(-22)). Individuals carrying an increasing number of risk alleles have an increasing risk for Crohn's disease, consistent with an independent effects multiplicative model (trend analysis p = 4.25 x 10(-23)). Patients with Crohn's disease with a more severe disease course, operations or an age of onset below 40 years have more risk alleles compared to non-stricturing, non-penetrating behaviour (p = 0.0008), no operations (p = 0.02) or age of onset above 40 years (p = 0.028). CONCLUSION: Crohn's disease is a multigenic disorder. An increase in the number of risk alleles is associated with an increased risk for the development of Crohn's disease and with a more severe disease course. Combining information from the known common risk polymorphisms may enable clinicians to predict the course of Crohn's disease

Stormflow generation in a small rain forest catchment in the Luquillo Experimental Forest, Puerto Rico.

Various complementary techniques were used to investigate the stormflow generating processes in a small headwater catchment in northeastern Puerto Rico. Over 100 samples were taken of soil matrix water, macropore flow, streamflow and precipitation, mainly during two storms of contrasting magnitude, for the analysis of calcium, magnesium, silicon, potassium, sodium and chloride. These were combined with hydrometric information on streamflow, return flow, precipitation, throughfall and soil moisture to distinguish water following different flow paths. Geo-electric sounding was used to survey the subsurface structure of the catchment, revealing a weathering front that coincided with the elevation of the stream channel instead of running parallel to surface topography. The hydrometric data were used in combination with soil physical data, a one-dimensional soil water model (VAMPS) and a three-component chemical mass-balance mixing model to describe the stormflow response of the catchment. It is inferred that most stormflow travelled through macropores in the top 20 cm of the soil profile. During a large event, saturation overland flow also accounted for a considerable portion of the stormflow, although it was not possible to quantify the associated volume fully. Although the mass-balance mixing model approach gave valuable information about the various flow paths within the catchment, it was not possible to distill the full picture from the model alone; additional hydrometric and soil physical evidence was needed to aid in the interpretation of the model results. © 2004 John Wiley and Sons, Ltd