Hi! I’m running into an issue where many of the regions have p-values of 0. This happens both when I use the provided reference data and when I supply my own LD panel. I’m also seeing p-values of 0 in cases where the estimated heritability is 0.
Could you help me understand why this might be happening? Thank you.
Here are the log files and results from a custom LD panel and marker selection:
ptsd.AB1_INTESTINAL_INFECTIONS.custom_panel.log
| chr |
piece |
eigen_use |
Heritability_1 |
P_value_Heritability_1 |
Heritability_2 |
P_value_Heritability_2 |
Genetic_Covariance |
Genetic_Correlation |
Lower_bound_rg |
Upper_bound_rg |
P |
| 18 |
1 |
0.95 |
4.19E-05 |
0.312522703 |
4.20E-06 |
0.392704765 |
1.33E-05 |
1 |
-0.4211421 |
1 |
0.10286742 |
| 18 |
2 |
0.95 |
7.26E-05 |
0 |
6.21E-07 |
0 |
6.72E-06 |
1 |
-0.9747975 |
1 |
0.1880255 |
| 18 |
3 |
0.95 |
7.78E-05 |
0.000141483 |
3.30E-05 |
0 |
1.29E-05 |
0.255325533 |
-0.3505351 |
0.7379738 |
0.44605861 |
And a subset of results for the supplied LD panel and markers:
ptsd.AB1_INTESTINAL_INFECTIONS_original_panel.log
I've also pulled out the section for Chr 1, region 18. The sample sizes are not small ( > 600k for GWAS 1 and GWAS 2) and the populations are of European ancestry.
Processing chromosome 1 region 18
0 SNPs were removed in GWAS 1 due to missing N or missing test statistic.
0 SNPs were removed in GWAS 2 due to missing N or missing test statistic.
479 out of 487 (98.36%) SNPs in reference panel are available in GWAS 1.
472 out of 487 (96.92%) SNPs in reference panel are available in GWAS 2.
Warning: More than 1% SNPs in reference panel are missed in GWAS 1. This may generate bias in estimation. Please make sure that you are using correct reference panel.
Warning: More than 1% SNPs in reference panel are missed in GWAS 2. This may generate bias in estimation. Please make sure that you are using correct reference panel.
0 SNPs were removed in GWAS 1 due to missing N or missing test statistic.
0 SNPs were removed in GWAS 2 due to missing N or missing test statistic.
383 out of 384 (99.74%) SNPs in reference panel are available in GWAS 1.
378 out of 384 (98.44%) SNPs in reference panel are available in GWAS 2.
Warning: More than 1% SNPs in reference panel are missed in GWAS 2. This may generate bias in estimation. Please make sure that you are using correct reference panel.
Point estimates:
Heritability of phenotype 1: 5.26e-06
Heritability of phenotype 2: 0.00e+00
Genetic Covariance: NA
Genetic Correlation: NA
Warning: Heritability of one trait was estimated to be 0, which may due to:
1) The true heritability is very small;
2) The sample size is too small;
3) Many SNPs in the chosen reference panel misses in the GWAS;
4) There is a severe mismatch between the GWAS population and the population for computing reference panel
| chr |
piece |
eigen_use |
Heritability_1 |
P_value_Heritability_1 |
Heritability_2 |
P_value_Heritability_2 |
Genetic_Covariance |
Genetic_Correlation |
Lower_bound_rg |
Upper_bound_rg |
P |
| 1 |
1 |
0.95 |
0 |
0.99999973 |
3.54E-06 |
0.70685257 |
NA |
NA |
NA |
NA |
NA |
| 1 |
2 |
0.95 |
2.54E-06 |
0.70028937 |
4.23E-06 |
0.41335605 |
-3.23E-06 |
-0.9857986 |
-1 |
1 |
0.47731132 |
| 1 |
3 |
0.95 |
0 |
0 |
0 |
0 |
NA |
NA |
NA |
NA |
NA |
| 1 |
4 |
0.95 |
0 |
0.99999934 |
1.37E-05 |
0.34554684 |
NA |
NA |
NA |
NA |
NA |
| 1 |
5 |
0.95 |
5.11E-05 |
0 |
3.90E-06 |
0.80454418 |
1.41E-05 |
1 |
0.07670767 |
1 |
0.0390007 |
| 1 |
6 |
0.95 |
4.98E-05 |
0.0401453 |
6.03E-06 |
0.39394398 |
1.13E-05 |
0.65316532 |
-0.570157 |
1 |
0.33607193 |
| 1 |
7 |
0.95 |
5.92E-05 |
0.027239 |
0 |
0 |
NA |
NA |
NA |
NA |
NA |
| 1 |
8 |
0.95 |
1.56E-05 |
0.22559855 |
0 |
0.99999962 |
NA |
NA |
NA |
NA |
NA |
| 1 |
9 |
0.95 |
0 |
0.99999934 |
2.35E-05 |
0.02610857 |
NA |
NA |
NA |
NA |
NA |
| 1 |
10 |
0.95 |
2.73E-06 |
0.92914007 |
0 |
0 |
NA |
NA |
NA |
NA |
NA |
| 1 |
11 |
0.95 |
4.08E-05 |
0.07575027 |
0 |
0.99999946 |
NA |
NA |
NA |
NA |
NA |
| 1 |
12 |
0.95 |
1.21E-05 |
0.35779579 |
0 |
0 |
NA |
NA |
NA |
NA |
NA |
| 1 |
13 |
0.95 |
6.94E-06 |
0.74282681 |
8.38E-06 |
0.35036598 |
7.63E-06 |
1 |
-0.0711071 |
1 |
0.05925121 |
| 1 |
14 |
0.95 |
2.72E-06 |
0.79844154 |
5.35E-06 |
0.47146716 |
-3.81E-06 |
-1 |
-1 |
1 |
0.26552321 |
| 1 |
15 |
0.95 |
3.55E-05 |
0 |
0 |
0 |
NA |
NA |
NA |
NA |
NA |
| 1 |
16 |
0.95 |
2.33E-06 |
0.94757092 |
0 |
0.99999899 |
NA |
NA |
NA |
NA |
NA |
| 1 |
17 |
0.95 |
0 |
0.99999973 |
7.02E-06 |
0.3469266 |
NA |
NA |
NA |
NA |
NA |
| 1 |
18 |
0.95 |
0 |
0 |
1.86E-05 |
0.20961767 |
NA |
NA |
NA |
NA |
NA |
Hi! I’m running into an issue where many of the regions have p-values of 0. This happens both when I use the provided reference data and when I supply my own LD panel. I’m also seeing p-values of 0 in cases where the estimated heritability is 0.
Could you help me understand why this might be happening? Thank you.
Here are the log files and results from a custom LD panel and marker selection:
ptsd.AB1_INTESTINAL_INFECTIONS.custom_panel.log
And a subset of results for the supplied LD panel and markers:
ptsd.AB1_INTESTINAL_INFECTIONS_original_panel.log
I've also pulled out the section for Chr 1, region 18. The sample sizes are not small ( > 600k for GWAS 1 and GWAS 2) and the populations are of European ancestry.
Processing chromosome 1 region 18
0 SNPs were removed in GWAS 1 due to missing N or missing test statistic.
0 SNPs were removed in GWAS 2 due to missing N or missing test statistic.
479 out of 487 (98.36%) SNPs in reference panel are available in GWAS 1.
472 out of 487 (96.92%) SNPs in reference panel are available in GWAS 2.
Warning: More than 1% SNPs in reference panel are missed in GWAS 1. This may generate bias in estimation. Please make sure that you are using correct reference panel.
Warning: More than 1% SNPs in reference panel are missed in GWAS 2. This may generate bias in estimation. Please make sure that you are using correct reference panel.
0 SNPs were removed in GWAS 1 due to missing N or missing test statistic.
0 SNPs were removed in GWAS 2 due to missing N or missing test statistic.
383 out of 384 (99.74%) SNPs in reference panel are available in GWAS 1.
378 out of 384 (98.44%) SNPs in reference panel are available in GWAS 2.
Warning: More than 1% SNPs in reference panel are missed in GWAS 2. This may generate bias in estimation. Please make sure that you are using correct reference panel.
Point estimates:
Heritability of phenotype 1: 5.26e-06
Heritability of phenotype 2: 0.00e+00
Genetic Covariance: NA
Genetic Correlation: NA
Warning: Heritability of one trait was estimated to be 0, which may due to:
1) The true heritability is very small;
2) The sample size is too small;
3) Many SNPs in the chosen reference panel misses in the GWAS;
4) There is a severe mismatch between the GWAS population and the population for computing reference panel