How to get gene level H4?

[mhaiyue]

Hi,

I am trying to run coloc.susie using GWAS summary statistics and GTEx data.
GTEx data is grouped by gene, I'm testing each gene at one time.
I get SNP level H4 from the result, how do I get gene level H4?

[chr1swallace]

the overall PP for H4 is returned in summary

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On Fri, 2022-05-13 at 02:32 -0700, mhaiyue wrote: Hi, I am trying to run coloc.susie using GWAS summary statistics and GTEx data. GTEx data is grouped by gene, I'm testing each gene at one time. I get SNP level H4 from the result, how do I get gene level H4? — Reply to this email directly, view it on GitHub, or unsubscribe. You are receiving this because you are subscribed to this thread.Message ID: ***@***.***>

[Leweibo]

There are a lot of PP.H4.abf in usie.res$summary.

How to interpret this coloc.susie results ？

susie.res$summary
nsnps hit1 hit2 PP.H0.abf PP.H1.abf PP.H2.abf PP.H3.abf PP.H4.abf idx1 idx2

1: 4591 rs12509595 rs1458038 0.000000e+00 4.147380e-13 0.000000e+00 0.02012341 9.798766e-01 1 1
2: 4591 rs10213506 rs1458038 1.570304e-273 1.878073e-11 8.361250e-263 1.00000000 6.399585e-12 2 1
3: 4591 rs74780855 rs1458038 5.954240e-106 1.878073e-11 3.170398e-95 1.00000000 1.328367e-13 3 1
4: 4591 rs72661739 rs1458038 1.556576e-79 1.878073e-11 8.288157e-69 1.00000000 1.963290e-13 4 1
5: 4591 rs10006582 rs1458038 1.476746e-59 1.878073e-11 7.863090e-49 1.00000000 6.277067e-13 5 1
6: 4591 rs6848130 rs1458038 2.330814e-86 1.878073e-11 1.241066e-75 1.00000000 2.036101e-09 6 1
7: 4591 rs2867702 rs1458038 1.508344e-52 1.878073e-11 8.031337e-42 1.00000000 3.088207e-13 7 1
8: 4591 rs10029510 rs1458038 6.966293e-45 1.878073e-11 3.709276e-34 1.00000000 1.354325e-12 8 1
9: 4591 rs7668598 rs1458038 1.734194e-52 1.878073e-11 9.233902e-42 1.00000000 1.516226e-12 9 1
10: 4591 rs1987331 rs1458038 1.352851e-41 1.878073e-11 7.203400e-31 1.00000000 3.023677e-13 10 1

[chr1swallace]

This means your first trait had 10 distinct credible sets in the susie results, and each line is the summary of colocalisation between each of these and the single signal found for the second trait. The first set appears to colocalise. I should note that when susie has found 10 signals for me, it has normally identified an issue with the LD meaning that many of the signals are false. One (not foolproof) diagnostic is to look at the marginal p values for the identified snps.

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-- https://chr1swallace.github.io<https://chr1swallace.github.io/>

________________________________ From: WB ***@***.***> Sent: Wednesday, March 20, 2024 8:50 AM To: chr1swallace/coloc ***@***.***> Cc: Chris Wallace ***@***.***>; State change ***@***.***> Subject: Re: [chr1swallace/coloc] How to get gene level H4? (Issue #87) There are a lot of PP.H4.abf in usie.res$summary. How to interpret this coloc.susie results ？ susie.res$summary nsnps hit1 hit2 PP.H0.abf PP.H1.abf PP.H2.abf PP.H3.abf PP.H4.abf idx1 idx2 1: 4591 rs12509595 rs1458038 0.000000e+00 4.147380e-13 0.000000e+00 0.02012341 9.798766e-01 1 1 2: 4591 rs10213506 rs1458038 1.570304e-273 1.878073e-11 8.361250e-263 1.00000000 6.399585e-12 2 1 3: 4591 rs74780855 rs1458038 5.954240e-106 1.878073e-11 3.170398e-95 1.00000000 1.328367e-13 3 1 4: 4591 rs72661739 rs1458038 1.556576e-79 1.878073e-11 8.288157e-69 1.00000000 1.963290e-13 4 1 5: 4591 rs10006582 rs1458038 1.476746e-59 1.878073e-11 7.863090e-49 1.00000000 6.277067e-13 5 1 6: 4591 rs6848130 rs1458038 2.330814e-86 1.878073e-11 1.241066e-75 1.00000000 2.036101e-09 6 1 7: 4591 rs2867702 rs1458038 1.508344e-52 1.878073e-11 8.031337e-42 1.00000000 3.088207e-13 7 1 8: 4591 rs10029510 rs1458038 6.966293e-45 1.878073e-11 3.709276e-34 1.00000000 1.354325e-12 8 1 9: 4591 rs7668598 rs1458038 1.734194e-52 1.878073e-11 9.233902e-42 1.00000000 1.516226e-12 9 1 10: 4591 rs1987331 rs1458038 1.352851e-41 1.878073e-11 7.203400e-31 1.00000000 3.023677e-13 10 1 — Reply to this email directly, view it on GitHub<#87 (comment)>, or unsubscribe<https://github.com/notifications/unsubscribe-auth/AAQWR2HYXLS7UBTKYRXVF23YZFEUDAVCNFSM5V2ZZEWKU5DIOJSWCZC7NNSXTN2JONZXKZKDN5WW2ZLOOQ5TEMBQHEYDKMZRGIZQ>. You are receiving this because you modified the open/close state.Message ID: ***@***.***>

[Leweibo]

Thanks for the response.

I didn't order the LD matrix for the SNPS previously. However, I reordered both SNPs of LD matrix and Snps of coloc$snp, and keep them in the same order. The ouput results are the same.
Both of the GWASs are from EUR population.

Some of the p values for the identified snps are not significant.

Here are the original P values:
trait 1

  Chr  Pos_b37       RSID Allele1 Allele2 Freq1    Effect    StdErr   P-value n_total_sum Pos_hg38
<int>    <int>     <char>  <char>  <char> <num>     <num>     <num>     <num>       <int>    <int>

1: 4 80674651 rs10006582 c g 0.740 -0.000779 0.0003916 4.683e-02 567207 79753497
2: 4 80936103 rs74780855 t c 0.990 0.001043 0.0017007 5.398e-01 504400 80014949
3: 4 81060836 rs2867702 a g 0.950 -0.001433 0.0010373 1.672e-01 419850 80139682
4: 4 81157098 rs6848130 t c 0.720 -0.001753 0.0004045 1.459e-05 524202 80235944
5: 4 81160459 rs7668598 t g 0.930 0.001577 0.0007088 2.610e-02 553983 80239305
6: 4 81164723 rs1458038 t c 0.300 0.003197 0.0003795 3.601e-17 558234 80243569
7: 4 81182554 rs12509595 t c 0.700 -0.003164 0.0003861 2.527e-16 525153 80261400
8: 4 81194251 rs10213506 t c 0.096 -0.001791 0.0005980 2.744e-03 567410 80273097
9: 4 81224787 rs10029510 t c 0.790 0.001322 0.0005620 1.865e-02 387545 80303633
10: 4 81827988 rs72661739 a g 0.250 0.000507 0.0005141 3.236e-01 388009 80906834
11: 4 81991163 rs1987331 c g 0.093 0.000979 0.0006301 1.204e-01 523248 81070009

trait 2 pQTL data from UKBppp

CHROM   GENPOS  RefSNP_id                    ID ALLELE1 ALLELE0       BETA         SE    A1FREQ      LOG10P
<int>    <int>     <char>                <char>  <char>  <char>      <num>      <num>     <num>       <num>

1: 4 79753497 rs10006582 4:80674651:C:G:imp:v1 G C -0.0139488 0.00816120 0.2625230 1.058380
2: 4 80014949 rs74780855 4:80936103:T:C:imp:v1 C T -0.0395698 0.03144000 0.0134996 0.681558
3: 4 80139682 rs2867702 4:81060836:A:G:imp:v1 G A 0.1673700 0.01916870 0.0420692 17.599500
4: 4 80235944 rs6848130 4:81157098:T:C:imp:v1 C T 0.4397370 0.00792346 0.2850770 670.664000
5: 4 80239305 rs7668598 4:81160459:T:G:imp:v1 G T -0.2435400 0.01484060 0.0617821 59.792800
6: 4 80243569 rs1458038 4:81164723:C:T:imp:v1 T C 0.6787440 0.00786273 0.2929920 1620.190000
7: 4 80261400 rs12509595 4:81182554:T:C:imp:v1 C T 0.6820780 0.00783308 0.2934170 1648.520000
8: 4 80273097 rs10213506 4:81194251:C:T:imp:v1 T C -0.5902380 0.01198100 0.0996872 528.809000
9: 4 80303633 rs10029510 4:81224787:T:C:imp:v1 C T -0.1676180 0.00908417 0.2093460 75.295800
10: 4 80906834 rs72661739 4:81827988:G:A:imp:v1 A G 0.0570774 0.00870352 0.2290970 10.263200
11: 4 81070009 rs1987331 4:81991163:G:C:imp:v1 C G 0.0568886 0.01275400 0.0884778 5.087300

[Leweibo]

Here is my coloc dataset.

https://e.pcloud.link/publink/show?code=XZeNH9Zh05TXIv8uSBHQWEhApGjaSNGryXV