Supplementary_Table_2 – Supplemental material for Different clinical outcomes in Crohn’s disease patients with esophagogastroduodenal, jejunal, and proximal ileal disease involvement: is L4 truly a single phenotype?

<p>Supplemental material, Supplementary_Table_2 for Different clinical outcomes in Crohn’s disease patients with esophagogastroduodenal, jejunal, and proximal ileal disease involvement: is L4 truly a single phenotype? by Ren Mao, Rui-Han Tang, Yun Qiu, Bai-Li Chen, Jing Guo, Sheng-Hong Zhang, Xue-Hua Li, Rui Feng, Yao He, Zi-Ping Li, Zhi-Rong Zeng, Rami Eliakim, Shomron Ben-Horin and Min-Hu Chen in Therapeutic Advances in Gastroenterology</p

Regions identified in the Ashkenazi Jewish CD GWAS, replication, and combined association analyses.

a<p>Physical position in megabases; Genome build NCBI36/hg18.</p>b<p>Genes highlighted by genetic location of the top SNP ±250 kb, ordered by proximity to the top SNP. If the top SNP is intragenic, the gene is indicated in bold font. Additionally, if there is evidence of eQTL effect of LOD≥5 this is indicated with a <i>♦</i> symbol and the LOD is given in brackets.</p>c<p>The risk allele in the AJ cohort with its frequency in healthy controls given in parenthesis.</p>d<p>The odds ratio for the risk allele in the replication cohort, with ±95% confidence intervals given in parenthesis.</p>e,f,g<p>p-values for the initial discovery GWAS for Crohn's disease in Ashkenazi Jews (Discovery p-value), replication cohort (Replication p-value) and a combined score of both p-values (Combined p-value) are given. Association significance thresholds are 5×10⁻⁸, 0.05, and 5×10⁻⁸ for discovery, replication and combined p-values, respectively. The significance thresholds of gene regions previously associated in other cohorts are 5×10⁻⁶, 0.05 and 5×10⁻⁶ for discovery, replication and combined p-values, respectively.</p

PCA analysis of the study participants.

<p>(A) PCA showing the first (X-axis) and second (Y-axis) eigenvectors plotting all 3,252 study participants (907 CD cases and 2,345 controls) across ∼22 K unlinked SNPs indicated by light blue open circles. Also included and color-coded in the graph are the four HapMap (<a href="http://www.hapmap.org" target="_blank">www.hapmap.org</a>) reference samples as solid triangles; CEPH-Utah (CEU; green), Yoruban-Nigeria (YRI; red), Han Chinese (CHB; orange) and Japanese (JPT; dark grey); and seven Jewish samples from the Jewish Hapmap project <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002559#pgen.1002559-Atzmon1" target="_blank">[2]</a> as solid circles, consisting of Ashkenazi Jews (AJ; blue), one European (Italian; purple), three Middle Eastern (Syrian; fuchsia, Iraqi; teal and Iranian; turquoise) and two Sephardic Jewish cohorts (Turkey; brown and Greek; orange). (B) The same analysis excluding the YRI and CHB+JPT reference panels. (C) A histogram of PC1 values for study participants (light blue) near the AJ cluster and intermediate between the AJ and CEU clusters. The histogram of PC1 values for the included samples show three distinct modes (Groups 1–3), with AJ reference (blue) and CEU (green) indicated.</p

Study cohort description.

<p>For each screen, the total number of individuals examined is shown (N_total), in addition to any Crohn's disease cases (NC_{D_cases}), non-Crohn's disease cases, which are a mix of individuals with Parkinson's disease, Schizophrenia, Type-2 Diabetes and Dystonia, (N_{non-CD_cases}), and non-diseased controls (N_controls).</p>b<p>Genotypes available for only a subset of 31 replication markers.</p

Regional plots of five novel associations to Crohn's disease in Ashkenazi Jews.

<p>Regional plots of the SNP p-values obtained in the discovery GWAS for a ±250 kb window around each of the 5 novel SNPs. The X-axis shows the chromosome and physical distance (kb), the left Y-axis shows the negative base ten logarithm of the p-value and the right y-axis shows recombination activity (cM/Mb) as a blue line. The chromosomal band is given above each plot. The replication SNP is indicated as a large red diamond, and linkage disequilibrium of surrounding SNPs with the replication SNP is indicated by a scale of intensity of red color filling as shown in the legend at the upper right hand corner of each plot. The combined discovery and replication p-value for the replication SNP is shown in blue, and is annotated with the SNP identifier and combined p-values. The position and location of any copy number variation in the mapping intervals are shown as a black rectangle. Positions, recombination rates and gene annotations are according the NCBI's build 36 (hg 18).</p

Association mapping of Crohn's disease in Ashkenazi Jews.

<p>(A) QQ-plots of the 100%, 75% and 50% AJ ancestry groups (Groups 1, 2 and 3, respectively). The inflation factors for the p-value distributions are given. For group 3, the p-values were genomic control-adjusted for over-inflation. (B) A Manhattan plot and QQ-plot (inset – in black) of the combined association scores from all three groups. The genome-wide threshold is shown in red and the replication threshold is shown in blue. The QQ-plot also shows association scores from all three groups but with 298 markers around the region of the <i>NOD2</i> signal on chromosome 16 removed before association mapping (in grey).</p