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ISCB2014_abstract_book

ISCB 2014 Vienna, Austria • Abstracts - Poster Presentations 135Wednesday, 27th August 2014 • 15:30-16:00 Monday25thAugustTuesday26thAugustThursday28thAugustAuthorIndexPostersWednesday27thAugustSunday24thAugust P4.4.192 Does a predisposition to kidney disease originate during prenatal development? A cohort study from the Born in Bradford Project HM Yuen1 , P Roderick1 , R Jeffrey2 , KM Godfrey3 , J West4 , J Wright4 1 PCPS, University of Southampton, Southampton, United Kingdom, 2 Bradford Teaching Hospitals NHS Foundation Trust, Bradford, United Kingdom, 3 MRC Lifecourse Epidemiology Unit, Southampton, United Kingdom, 4 Bradford Institute for Health Research, Bradford, United Kingdom   Background: Rates of advanced chronic kidney disease (CKD) and renal replacement therapy are higher in South Asian compared to White British populations. Low birthweight (LBW) is also more frequent in South Asian populations; LBW has been associated with increased risk of chronic kid- ney disease which maybe due to reduced number of nephrons at birth. Aim: To measure foetal kidney size measured from ultrasound scans in South Asian and White British pregnant women at 34 weeks gestation. Methods: Kidney dimensions (transverse diameter, antero-posterior di- ameter, length, and circumference) and derived volume were assessed in a random sample of 872 White British and 715 South Asian women who were participants in the Born in Bradford cohort study. Kidney measures were compared between ethnic groups, unadjusted and adjusted for ma- ternal age, socio-economic factors, marital status, body mass index, smok- ing and alcohol use in pregnancy, parity, baby’s gender and birthweight for gestational age. Results: Birthweight for gestational age at 40 weeks was 200g less in South Asian compared to White British babies. Mean kidney volume for gestational age was 8.79 cm3 in South Asian and 10.45cm3 in White British babies, a difference of 1.66cm3 (95%CI -1.93 to -1.40, p<0.001). The differ- ence was robust to adjustment for the potential confounders mentioned above (adjusted difference 1.38cm3 , 95%CI -1.84 to -0.97, p<0.001). There were smaller reductions in other foetal measures. Conclusions: South Asians babies have smaller kidneys compared to White British babies, even after adjusting for potential confounders in- cluding birthweight. This finding may partly explain the increased risk of adult CKD.   P4.5 Other P4.5.6 Meta-analysis of genome-wide gene-environment interactions on colorectal cancer H Alonso1 , U Peters2 , J Gauderman3 , T Harrison2 , L Hsu2 , PT Campbell4 , D Thomas3 , SB Gruber3 , V Moreno1 1 Catalan Institute of Oncology, Hospitalet del Llobregat, Spain, 2 Fred Hutchinson Cancer Research Center, Seattle, United States, 3 University of Southern California, Los Angeles, United States, 4 American Cancer Society, Atlanta, United States   Susceptibility loci identified so far for colorectal cancer (CRC) only account for a small fraction of the estimated inheritance. We have undertaken an exhaustive analysis of gene-environment (GxE) interactions aiming to identify novel susceptibility loci for CRC in 6 GWAS within the ColoRectal Transdisciplinary Study (CORECT) Consortium. Here we explore diverse statistical methods to identify GxE and meta-analyze the results. The GWAS studies contribute with 3927 cases and 4203 controls that have been genotyped with a custom array (1.3M SNPs). Whole genome varia- tion has been imputed using the 1000 Genomes Project panel. After a QC and filtering protocol (MAF>0.01, LD<0.99), more than 4.5 million SNPs have been analyzed for GxE interactions. Here we analyze BMI and height, variables that have been centrally harmo- nized through a standardized process and individual level data are avail- able for all analysis. Diverse statistical models have been used to scan for GxE interactions, including logistic regression for case-control (CC), case- only (CO) analysis, empirical Bayes (EB), as well as more powerful 2-step procedures, such as the cocktail (Hsu et al., 2012) and EDGxE (Gauderman et al., 2013) methods. All of these procedures were implemented in the GxEScan software program (http://biostats.usc.edu/software). A weighted testing approach has been used for two-step methods to im- prove the likelihood of capturing significant interactions while multiple testing is controlled. To combine the results of each study, meta-analytical techniques have been used: combination of p-values, z-values, odds-ra- tios. These are compared with a pool-analysis of all studies combined with fixed and random effects models. On behalf of CORECT, ColoRectal Transdisciplinary Study   P4.5.9 Dutch national cohort for environmental health issues. The DUELS Study C Ameling1 , M Marra1 1 National Institute for Public Health and the Environment, Bilthoven, The Netherlands   Background: Databases concerning population exposure to e.g. noise, air pollution and available green space in the Netherlands are available at increasing geographical resolution. These data can be combined with data on an individual level for all Dutch residents. A retrospective cohort combining exposure and mortality was built. Aims: To allow assessment of the association of several types of individual exposure with cause specific mortality in the Dutch population. Methods: Local environmental exposures such as air pollution, noise and available green space where linked to 98% of all addresses in the Netherlands. Based on this linkage, demographic and mortality data were generated for the ~15 million Dutch residents on 1 January 2004. Records from the municipal registration were available from 1 January 1995 through 31 December 2010. For an initial analysis ~9 million persons of all ages who had resided at the same address for at least five years be- fore 2004 were selected. Survival analysis was carried out on ~7 million persons over 30 years of age using Cox’ proportional hazards regression model. Hazard rate estimates for several causes of death for five-year resi- dential exposure to various environmental risk factors were determined, adjusted for confounders at the individual level. Results: Several of the available environmental risk factors showed a sta- tistically significant linear association with increased mortality. Detailed results will be presented. Conclusion: The cohort provides a valuable data source for analyzing and monitoring the association between environmental risk factors at a rela- tively high geographical resolution and mortality in the Dutch population.

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