Table 1. Genetic Correlation and Genetic Overlap Estimations Between 24 Pairwise Traitsa.
Trait pair | Genetic correlation | Genetic overlap | |||||
---|---|---|---|---|---|---|---|
Genetic correlation (SE) | P value for LDSC | Intercept (SE) | P value for intercept | PM 11 | PARb | P value for GPA | |
IBD-MDDc,d | 0.1706 (0.0407) | 2.82 × 10−5 | 0.0003 (0.0055) | 9.57 × 10−1 | 0.0116 | 0.0473 | 1.41 × 10−3 |
IBD-PTSD | 0.1742 (0.0377) | 7.39 × 10−2 | 0.0049 (0.0051) | 3.37 × 10−1 | 0.0038 | 0.0189 | 2.27 × 10−1 |
IBD-SCZd | 0.0359 (0.0403) | 3.73 × 10−1 | 0.0004 (0.0062) | 9.49 × 10−1 | 0.0167 | 0.0605 | 6.07 × 10−15 |
IBD-ADHD | –0.0045 (0.0599) | 9.40 × 10−1 | 0.0121 (0.0057) | 3.38 × 10−2 | 0.0121 | 0.0512 | 5.16 × 10−2 |
IBD-BIPd | 0.0221 (0.0478) | 6.45 × 10−1 | 0.0064 (0.0063) | 3.10 × 10−1 | 0.0194 | 0.0828 | 3.80 × 10−28 |
IBD-ANd | –0.0296 (0.0630) | 6.38 × 10−1 | 0.0019 (0.0063) | 7.63 × 10−1 | 0.0206 | 0.0851 | 8.85 × 10−11 |
IBS-MDDc,d,e | 0.5705 (0.0256) | 1.14 × 10−109 | 0.0795 (0.0066) | 2.05 × 10−33 | 0.1571 | 0.7791 | <1 × 10−300 |
IBS-PTSDc,d,e | 0.4720 (0.0795) | 2.87 × 10−9 | 0.0275 (0.0049) | 2.00 × 10−8 | 0.0422 | 0.1504 | 1.27 × 10−5 |
IBS-SCZc,d | 0.1711 (0.0285) | 1.85 × 10−9 | –0.0025 (0.006) | 6.77 × 10−1 | 0.1246 | 0.4130 | <1 × 10−300 |
IBS-ADHDc,d | 0.2060 (0.0405) | 3.73 × 10−7 | 0.0138 (0.0059) | 1.93 × 10−2 | 0.1155 | 0.3895 | 1.67 × 10−87 |
IBS-BIPc,d,e | 0.1269 (0.0305) | 3.12 × 10−5 | 0.0219 (0.0058) | 1.59 × 10−4 | 0.1183 | 0.4579 | 3.54 × 10−268 |
IBS-ANc,d | 0.1536 (0.0413) | 2.00 × 10−4 | 0.0003 (0.0064) | 9.63 × 10−1 | 0.1207 | 0.4059 | 3.98 × 10−86 |
PUD-MDDc,d,e | 0.4438 (0.0437) | 3.31 × 10−24 | 0.0333 (0.0059) | 1.66 × 10−8 | 0.0987 | 0.4011 | 1.04 × 10−102 |
PUD-PTSDc | 0.5448 (0.1120) | 1.15 × 10−6 | 0.0074 (0.0046) | 1.08 × 10−1 | 0.0274 | 0.1052 | 3.65 × 10−2 |
PUD-SCZc,d | 0.1306 (0.0402) | 1.20 × 10−3 | –0.0007 (0.006) | 9.07 × 10−1 | 0.0832 | 0.2713 | 7.89 × 10−55 |
PUD-ADHDc,d | 0.4771 (0.0579) | 1.63 × 10−16 | 0.0072 (0.0058) | 2.14 × 10−1 | 0.0886 | 0.3409 | 1.27 × 10−37 |
PUD-BIPd | 0.0691 (0.0437) | 1.14 × 10−1 | 0.0023 (0.0054) | 6.70 × 10−1 | 0.0679 | 0.2491 | 1.31 × 10−34 |
PUD-ANd | 0.0366 (0.0539) | 4.97 × 10−1 | 0.0014 (0.0056) | 8.03 × 10−1 | 0.0448 | 0.1441 | 8.03 × 10−4 |
GERD–MDDc,d,e | 0.4596 (0.0267) | 3.50 × 10−66 | 0.0692 (0.0053) | 5.83 × 10−39 | 0.1762 | 0.6824 | <1 × 10−300 |
GERD-PTSDc,d | 0.4193 (0.0690) | 1.24 × 10−9 | 0.0156 (0.0051) | 2.22 × 10−3 | 0.0538 | 0.1567 | 3.43 × 10−4 |
GERD-SCZd | 0.0313 (0.0273) | 2.51 × 10−1 | 0.0107 (0.0062) | 8.44 × 10−2 | 0.1299 | 0.3596 | 1.07 × 10−189 |
GERD-ADHDc,d | 0.4919 (0.0371) | 3.32 × 10−40 | –0.0003 (0.0063) | 9.62 × 10−1 | 0.1543 | 0.4844 | 6.81 × 10−132 |
GERD-BIPd | 0.0332 (0.0308) | 2.81 × 10−01 | 0.0048 (0.0059) | 4.16 × 10−1 | 0.1279 | 0.4050 | 1.27 × 10−174 |
GERD-ANd | 0.0179 (0.0386) | 6.43 × 10−1 | 0.0038 (0.0063) | 5.46 × 10−1 | 0.1265 | 0.3597 | 1.24 × 10−61 |
Abbreviations: ADHD, attention-deficit/hyperactivity disorder; AN, anorexia nervosa; BIP, bipolar disorder; GERD, gastroesophageal reflux disease; GPA, genetic analysis incorporating pleiotropy and annotation method; IBD, inflammatory bowel disease; IBS, irritable bowel syndrome; LDSC, linkage disequilibrium score regression; MDD, major depressive disorder; PAR, pleiotropy association ratio; PM 11, proportion of genetic variants associated with both traits; PTSD, posttraumatic stress disorder; PUD, peptic ulcer disease; SCZ, schizophrenia.
Genetic correlation and genetic overlap were estimated by LDSC and GPA methods, respectively. Bonferroni-corrected significance threshold was set at P < 2.83 × 10−3 (.05/24), producing a final union set of 22 pairwise traits with significant genetic correlation or genetic overlap for subsequent analysis.
We introduced PAR as PM 11/(PM 10 + PM 01 + PM 11) to represent the proportion of pleiotropic single-nucleotide variations (SNVs) associated with both traits against the proportion of SNVs associated with at least 1 trait.
Pairwise trait with significant genetic correlation.
Pairwise trait with significant genetic overlap.
Genome-wide association study summary data with potentially significant sample overlap.