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jwr-git / pwcoco

Pair-wise conditional analysis and colocalisation
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NA values in conditional colocalisation analyses #15

Closed Jingxian-Huang closed 4 months ago

Jingxian-Huang commented 5 months ago

Hi,

We are encountering many NA values in conditional colocalisation results. The results for unconditional colocalisation are just fine. As I checked the log file, everything seem quite normal. I'm wondering what would be the reason for that. Thank you very much.

Here is a part of the log file:

[2024-04-15 05:29:05.741] [pwcoco_log] [info] Phenotypic variance estimated from summary statistcs of all SNPs: 30.50 [2024-04-15 05:29:06.000] [pwcoco_log] [info] Colocalisation analysis initialised with 3531 SNPs. [2024-04-15 05:29:06.002] [pwcoco_log] [info] Unconditioned colocalisation results. [2024-04-15 05:29:06.002] [pwcoco_log] [info] H0: 0.00; H1: 0.32; H2: 0.00; H3: 0.67; H4: 0.01; abf_all: 695.85. [2024-04-15 05:29:06.006] [pwcoco_log] [info] Reading data from bim file: UKB/UKB_ref_panel_38.bim. [2024-04-15 05:29:21.635] [pwcoco_log] [info] Number of SNPs read from .bim file: 600390. [2024-04-15 05:29:32.550] [pwcoco_log] [info] Number of SNPs matched from .bim file to the phenotype data: 4537. [2024-04-15 05:29:32.617] [pwcoco_log] [info] Reading data from fam file:UKB/UKB_ref_panel_38.fam. [2024-04-15 05:29:32.636] [pwcoco_log] [info] Successfully read 10000 individuals from .fam file. [2024-04-15 05:29:37.543] [pwcoco_log] [info] Finished reading .bed file. Genotype data for 10000 individuals and 4537 SNPs read. [2024-04-15 05:29:37.544] [pwcoco_log] [info] Filtering SNPs with MAF <= 0.01. [2024-04-15 05:29:37.550] [pwcoco_log] [info] After filtering based on MAF, there are 4394 SNPs remaining in the analysis (amount removed: 143). [2024-04-15 05:29:37.584] [pwcoco_log] [info] [ebi-a-GCST90013993.txt] Total amount of SNPs matched from phenotype file with reference SNPs are: 3917. [2024-04-15 05:29:39.345] [pwcoco_log] [info] [ebi-a-GCST90013993.txt] Performing stepwise model selection on 3917 SNPs; p cutoff = 5e-08, collinearity = 0.9 assuming complete LE between SNPs more than 10.0 Mb away). [2024-04-15 05:29:39.346] [pwcoco_log] [info] [ebi-a-GCST90013993.txt] Selected SNP rs12721030 with chisq 1329.55 and pval 4.29e-291. [2024-04-15 05:29:43.781] [pwcoco_log] [info] [ebi-a-GCST90013993.txt] Selected entry SNP rs3133352 with cpval 2.12e-84. [2024-04-15 05:29:48.253] [pwcoco_log] [info] [ebi-a-GCST90013993.txt] Selected entry SNP rs2513099 with cpval 1.38e-35. [2024-04-15 05:29:52.674] [pwcoco_log] [info] [ebi-a-GCST90013993.txt] Selected entry SNP rs187676162 with cpval 6.73e-24. [2024-04-15 05:29:57.164] [pwcoco_log] [info] [ebi-a-GCST90013993.txt] Selected entry SNP rs144015791 with cpval 1.94e-23. [2024-04-15 05:30:01.582] [pwcoco_log] [info] [ebi-a-GCST90013993.txt] 5 associated SNPs have been selected. [2024-04-15 05:30:01.651] [pwcoco_log] [info] [ebi-a-GCST90013993.txt] Selected entry SNP rs4938415 with cpval 3.46e-23. [2024-04-15 05:30:06.179] [pwcoco_log] [info] [ebi-a-GCST90013993.txt] Selected entry SNP rs111884008 with cpval 2.89e-23. [2024-04-15 05:30:10.677] [pwcoco_log] [info] [ebi-a-GCST90013993.txt] Selected entry SNP rs10790170 with cpval 2.97e-11. [2024-04-15 05:30:15.218] [pwcoco_log] [info] [ebi-a-GCST90013993.txt] Selected entry SNP rs117106280 with cpval 6.25e-12. [2024-04-15 05:30:19.803] [pwcoco_log] [info] [ebi-a-GCST90013993.txt] Selected entry SNP rs139254418 with cpval 2.05e-09. [2024-04-15 05:30:24.237] [pwcoco_log] [info] [ebi-a-GCST90013993.txt] 10 associated SNPs have been selected. [2024-04-15 05:30:24.399] [pwcoco_log] [info] [ebi-a-GCST90013993.txt] Selected entry SNP rs508731 with cpval 8.54e-10. [2024-04-15 05:30:29.046] [pwcoco_log] [info] [ebi-a-GCST90013993.txt] Selected entry SNP rs7947434 with cpval 2.83e-07. [2024-04-15 05:30:29.046] [pwcoco_log] [info] [ebi-a-GCST90013993.txt] rs7947434 does not meet threshold [2024-04-15 05:30:29.046] [pwcoco_log] [info] [ebi-a-GCST90013993.txt] Finally, 11 associated SNPs have been selected. [2024-04-15 05:30:29.046] [pwcoco_log] [info] [ebi-a-GCST90013993.txt] (0 SNPs eliminated by backward selection.) [2024-04-15 05:30:29.068] [pwcoco_log] [info] [GTEx_Analysis_v8_QTLs_GTEx_Analysis_v8_eQTL_all_associations_Brain_Anterior_cingulate_cortex_BA24.allpairs.txt] There were 476 SNPs that had a large difference in the allele frequency to that of the reference sample. [2024-04-15 05:30:29.084] [pwcoco_log] [info] [GTEx_Analysis_v8_QTLs_GTEx_Analysis_v8_eQTL_all_associations_Brain_Anterior_cingulate_cortex_BA24.allpairs.txt] Total amount of SNPs matched from phenotype file with reference SNPs are: 2969. [2024-04-15 05:30:30.472] [pwcoco_log] [info] [GTEx_Analysis_v8_QTLs_GTEx_Analysis_v8_eQTL_all_associations_Brain_Anterior_cingulate_cortex_BA24.allpairs.txt] Performing stepwise model selection on 2969 SNPs; p cutoff = 5e-06, collinearity = 0.9 assuming complete LE between SNPs more than 10.0 Mb away). [2024-04-15 05:30:30.473] [pwcoco_log] [info] [GTEx_Analysis_v8_QTLs_GTEx_Analysis_v8_eQTL_all_associations_Brain_Anterior_cingulate_cortex_BA24.allpairs.txt] Selected SNP rs78218374 with chisq 23.08 and pval 1.55e-06. [2024-04-15 05:30:33.773] [pwcoco_log] [info] [GTEx_Analysis_v8_QTLs_GTEx_Analysis_v8_eQTL_all_associations_Brain_Anterior_cingulate_cortex_BA24.allpairs.txt] Selected entry SNP rs6589580 with cpval 4.75e-04. [2024-04-15 05:30:33.773] [pwcoco_log] [info] [GTEx_Analysis_v8_QTLs_GTEx_Analysis_v8_eQTL_all_associations_Brain_Anterior_cingulate_cortex_BA24.allpairs.txt] rs6589580 does not meet threshold [2024-04-15 05:30:33.773] [pwcoco_log] [info] [GTEx_Analysis_v8_QTLs_GTEx_Analysis_v8_eQTL_all_associations_Brain_Anterior_cingulate_cortex_BA24.allpairs.txt] Finally, 1 associated SNPs have been selected. [2024-04-15 05:30:33.773] [pwcoco_log] [info] [GTEx_Analysis_v8_QTLs_GTEx_Analysis_v8_eQTL_all_associations_Brain_Anterior_cingulate_cortex_BA24.allpairs.txt] (0 SNPs eliminated by backward selection.) [2024-04-15 05:30:33.773] [pwcoco_log] [info] There are 11 selected SNPs in the exposure dataset and 1 in the outcome dataset. [2024-04-15 05:30:33.773] [pwcoco_log] [info] Performing 11 conditional and colocalisation analyses. [2024-04-15 05:31:06.752] [pwcoco_log] [info] Colocalisation analysis initialised with 2886 SNPs. [2024-04-15 05:31:06.754] [pwcoco_log] [info] Conditioned results for SNP1: rs10790170, SNP2: rs78218374 [2024-04-15 05:31:06.754] [pwcoco_log] [info] H0: -nan; H1: -nan; H2: -nan; H3: -nan; H4: -nan; abf_all: -nan. [2024-04-15 05:31:06.924] [pwcoco_log] [info] Colocalisation analysis initialised with 2901 SNPs. [2024-04-15 05:31:06.925] [pwcoco_log] [info] Conditioned results for SNP1: rs10790170, SNP2: unconditioned [2024-04-15 05:31:06.925] [pwcoco_log] [info] H0: 0.00; H1: 0.33; H2: 0.00; H3: 0.64; H4: 0.03; abf_all: 16.22. [2024-04-15 05:31:39.124] [pwcoco_log] [info] Colocalisation analysis initialised with 2918 SNPs. [2024-04-15 05:31:39.126] [pwcoco_log] [info] Conditioned results for SNP1: rs111884008, SNP2: rs78218374 [2024-04-15 05:31:39.126] [pwcoco_log] [info] H0: -nan; H1: -nan; H2: -nan; H3: -nan; H4: -nan; abf_all: -nan. [2024-04-15 05:31:39.298] [pwcoco_log] [info] Colocalisation analysis initialised with 2933 SNPs. [2024-04-15 05:31:39.300] [pwcoco_log] [info] Conditioned results for SNP1: rs111884008, SNP2: unconditioned [2024-04-15 05:31:39.300] [pwcoco_log] [info] H0: 0.00; H1: 0.23; H2: 0.00; H3: 0.46; H4: 0.31; abf_all: 39.48. [2024-04-15 05:32:11.496] [pwcoco_log] [info] Colocalisation analysis initialised with 2886 SNPs. [2024-04-15 05:32:11.498] [pwcoco_log] [info] Conditioned results for SNP1: rs117133249, SNP2: rs78218374 [2024-04-15 05:32:11.498] [pwcoco_log] [info] H0: -nan; H1: -nan; H2: -nan; H3: -nan; H4: -nan; abf_all: -nan. [2024-04-15 05:32:11.671] [pwcoco_log] [info] Colocalisation analysis initialised with 2901 SNPs. [2024-04-15 05:32:11.673] [pwcoco_log] [info] Conditioned results for SNP1: rs117133249, SNP2: unconditioned [2024-04-15 05:32:11.673] [pwcoco_log] [info] H0: 0.00; H1: 0.34; H2: 0.00; H3: 0.66; H4: 0.01; abf_all: 10.84. [2024-04-15 05:32:43.900] [pwcoco_log] [info] Colocalisation analysis initialised with 2889 SNPs. [2024-04-15 05:32:43.902] [pwcoco_log] [info] Conditioned results for SNP1: rs12721030, SNP2: rs78218374 [2024-04-15 05:32:43.902] [pwcoco_log] [info] H0: -nan; H1: -nan; H2: -nan; H3: -nan; H4: -nan; abf_all: -nan. [2024-04-15 05:32:44.070] [pwcoco_log] [info] Colocalisation analysis initialised with 2904 SNPs. [2024-04-15 05:32:44.072] [pwcoco_log] [info] Conditioned results for SNP1: rs12721030, SNP2: unconditioned [2024-04-15 05:32:44.072] [pwcoco_log] [info] H0: 0.00; H1: 0.33; H2: 0.00; H3: 0.65; H4: 0.02; abf_all: 156.77. [2024-04-15 05:33:18.792] [pwcoco_log] [info] Colocalisation analysis initialised with 2894 SNPs. [2024-04-15 05:33:18.794] [pwcoco_log] [info] Conditioned results for SNP1: rs139462136, SNP2: rs78218374 [2024-04-15 05:33:18.794] [pwcoco_log] [info] H0: -nan; H1: -nan; H2: -nan; H3: -nan; H4: -nan; abf_all: -nan. [2024-04-15 05:33:19.009] [pwcoco_log] [info] Colocalisation analysis initialised with 2909 SNPs. [2024-04-15 05:33:19.012] [pwcoco_log] [info] Conditioned results for SNP1: rs139462136, SNP2: unconditioned [2024-04-15 05:33:19.012] [pwcoco_log] [info] H0: 0.00; H1: 0.34; H2: 0.00; H3: 0.65; H4: 0.01; abf_all: 9.41. [2024-04-15 05:33:52.280] [pwcoco_log] [info] Colocalisation analysis initialised with 2886 SNPs. [2024-04-15 05:33:52.282] [pwcoco_log] [info] Conditioned results for SNP1: rs144018203, SNP2: rs78218374 [2024-04-15 05:33:52.282] [pwcoco_log] [info] H0: -nan; H1: -nan; H2: -nan; H3: -nan; H4: -nan; abf_all: -nan.

jwr-git commented 4 months ago

Hello, I suspect this is happening because there is only one signal in the eQTL dataset and the models do not really hold up when conditioning upon a singular, sub-threshold signal within a region. In this case, I would personally not have reduced the P value threshold to force the selection of rs78218374 in the eQTL dataset, since I suspect what you are more interested in is which of the signals in the ApoA dataset colocalises with the eQTL.