Enrichment of GWAS signals for the nearest RefSeq genes to the TCF7L2 binding site in all eight cell lines
| Percentage of total hg19 gene list | Percentage of ChIP-seq gene list | p Values: χ2 | Percentage of total hg19 gene list | Percentage of ChIP-seq gene list | p Values: χ2 | |
|---|---|---|---|---|---|---|
| HCT116: 750 genes | HEPG2 (ENCODE): 1924 genes | |||||
| Endocrine | 3.9 (750/19 015) | 7.3 (64.66/888) | 2.69×10−6 | 10.1 (1924/19 015) | 19.7 (175.34/888) | 3.38×10−15 |
| T2D | 3.9 (750/19 015) | 11.0 (9/82) | 0.0025 | 10.1 (1924/19 015) | 21.7 (17.83/82) | 0.0024 |
| Cancer | 3.9 (750/19 015) | 10.7 (35.87/335) | 5.81×10−9 | 10.1 (1924/19 015) | 22.0 (73.86/335) | 9.17×10−10 |
| Cardiovascular | 3.9 (750/19 015) | 7.8 (36.19/463) | 9.33×10−5 | 10.1 (1924/19 015) | 21.3 (98.41/463) | 3.34×10−11 |
| Inflammation | 3.9 (750/19 015) | 7.2 (37.32/521) | 0.00 062 | 10.1 (1924/19 015) | 16.3 (85.1/521) | 5.40×10−5 |
| Neuropsychiatric | 3.9 (750/19 015) | 5.7 (33/584) | 0.048 | 10.1 (1924/19 015) | 13.5 (78.67/584) | 0.023 |
| All | 3.9 (750/19 015) | 5.9 (212.25/3607) | 5.06×10−7 | 10.1 (1924/19 015) | 15.0 (541.21/3607) | 2.58×10−14 |
| HeLa exons (4–16): 1983 genes | HEPG2 (in-house): 2435 genes | |||||
| Endocrine | 10.4 (1983/19 015) | 16.8 (148.86/888) | 1.64×10−7 | 12.8 (2435/19 015) | 21.3 (188.73/888) | 6.18×10−10 |
| T2D | 10.4 (1983/19 015) | 17.5 (14.33/82) | 0.086 | 12.8 (2435/19 015) | 23.8 (19.5/82) | 0.0088 |
| Cancer | 10.4 (1983/19 015) | 19.8 (62.21/335) | 3.41×10−5 | 12.8 (2435/19 015) | 23.7 (79.29/335) | 1.04×10−6 |
| Cardiovascular | 10.4 (1983/19 015) | 20.0 (92.50/463) | 9.18×10−9 | 12.8 (2435/19 015) | 24.4 (113.02/463) | 9.30×10−10 |
| Inflammation | 10.4 (1983/19 015) | 14.0 (73.13/521) | 0.02 | 12.8 (2435/19 015) | 15.4 (80.43/521) | 0.14 |
| Neuropsychiatric | 10.4 (1983/19 015) | 12.5 (72.94/584) | 0.15 | 12.8 (2435/19 015) | 18.2 (106/584) | 0.0011 |
| All | 10.4 (1983/19 015) | 14.0 (506.47/3607) | 2.02×10−8 | 12.8 (2435/19 015) | 17.5 (629.71/3607) | 1.09×10−10 |
| HEK293: 3519 genes | MCF7: 3863 genes | |||||
| Endocrine | 18.5 (3519/19 015) | 32.5 (288.23/888) | 6.46×10−16 | 20.3 (3863/19 015) | 31.9 (283.57/888) | 8.36×10−11 |
| T2D | 18.5 (3519/19 015) | 37.2 (30.5/82) | 0.00 057 | 20.3 (3863/19 015) | 36.0 (29.5/82) | 0.0053 |
| Cancer | 18.5 (3519/19 015) | 32.0 (107.19/335) | 9.26×10−7 | 20.3 (3863/19 015) | 32.0 (107.09/335) | 4.97×10−5 |
| Cardiovascular | 18.5 (3519/19 015) | 36.6 (169.37/463) | 4.74×10−14 | 20.3 (3863/19 015) | 35.6 (164.92/463) | 7.28×10−10 |
| Inflammation | 18.5 (3519/19 015) | 25.9 (134.85/521) | 0.00 058 | 20.3 (3863/19 015) | 28.7 (149.47/521) | 0.0002 |
| Neuropsychiatric | 18.5 (3519/19 015) | 31.2 (182.4/584) | 1.33×10−9 | 20.3 (3863/19 015) | 25.2 (147/584) | 0.022 |
| All | 18.5 (3519/19 015) | 27.4 (988.25/3607) | 1.54×10−22 | 20.3 (3863/19 015) | 28.3 (1019.56/3607) | 5.47×10−17 |
| PANC1: 5123 genes | HeLa exons (1–3): 6451 genes | |||||
| Endocrine | 26.9 (5123/19 015) | 34.5 (306.16/888) | 0.00 029 | 33.9 (6451/19 015) | 42.0 (372.76/888) | 0.00 073 |
| T2D | 26.9 (5123/19 015) | 44.5 (36.5/82) | 0.0087 | 33.9 (6451/19 015) | 47.4 (38.83/82) | 0.082 |
| Cancer | 26.9 (5123/19 015) | 36.5 (122.21/335) | 0.0047 | 33.9 (6451/19 015) | 47.9 (160.32/335) | 0.00 041 |
| Cardiovascular | 26.9 (5123/19 015) | 35.1 (162.48/463) | 0.0037 | 33.9 (6451/19 015) | 49.9 (230.9/463) | 2.13×10−6 |
| Inflammation | 26.9 (5123/19 015) | 31.1 (161.98/521) | 0.12 | 33.9 (6451/19 015) | 38.8 (202.03/521) | 0.11 |
| Neuropsychiatric | 26.9 (5123/19 015) | 29.0 (169.5/584) | 0.38 | 33.9 (6451/19 015) | 37.7 (220.2/584) | 0.19 |
| All | 26.9 (5123/19 015) | 30.3 (1094.66/3607) | 0.0016 | 33.9 (6451/19 015) | 38.0 (1369.44/3607) | 0.0013 |
We based our analysis on all GWAS genes summarized in the NHGRI GWAS catalog (http://www.genome.gov/gwastudies) from 19 February 2013. Enrichment was investigated using a χ2 analysis. Our method of scoring the GWAS ChIP-seq gene overlap was to assign 1 point to a GWAS region where all the genes in the region were found in our list, and a fraction of a point determined by how many genes were found in our gene list divided by the total genes in the GWAS region. This analysis model would equally weight a GWAS region with 1 gene the same as a region with 8 genes as a single region.
ChIP, chromatin immunoprecipitation; GWAS, genome-wide association studies; T2D , type 2 diabetes; TCF7L2, transcription factor 7-like 2.