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The association between EIL and disease odds was estimated using a logistic generalized additive model (Hastie et?al. 2009). Tests for significant differences between groups were assessed using Wilcoxon FKBPL rank-sum tests (two-sided tests were used when testing the null hypothesis of no difference in EIL between cases and controls against the alternative hypothesis that EIL differs in cases and controls; one-sided tests were used when testing the null hypothesis of no difference in EIL between cases and controls against the alternative hypothesis that EIL is raised in cases). All P-values were false-discovery rate (FDR) adjusted using the Benjamini and Hochberg (1995) procedure. Results We did not observe any difference in EIL (RGI normalized by the number of loci genotyped, EIL) between the three different control sets (1958, NBS and ABCFS controls) indicating that the background measure �� was reliably estimated; similarly, no difference in EIL between the POSH and ABCFS cases was observed (Fig.?(Fig.1B1B and C). However, EIL was significantly selleck screening library higher in both the POSH and ABCFS cases than the three sets of reference controls (FDR adjusted P?Trametinib research buy of RGI in amalgamated case set and amalgamated control set revealed significant differences in distribution structure (P?=?4.3?��?10?10, two-sample Kolmogorov�CSmirnov test) with the case distribution having a substantially heavier tail than the control distribution, indicating a greater proportion of samples with higher EIL (Fig.?(Fig.1D).1D). To investigate further we conducted regression using a logistic generalized additive model (Hastie et?al. 2009) in order to estimate the relationship between disease odds and EIL (Fig.?(Fig.1E).1E). Consistent with the heavy-tailed nature of the case distribution we observed a strong positive association between odds ratio and EIL. In particular, the odds ratio increased sharply for EIL above 1.75, with the highest percentile EIL (above 1.183) having an odds ratio greater than 12 by comparison with the lower 99% (P?