<p>The question has been answered in the bioStars forum: <a href="https://www.biostars.org/p/428314/" rel="nofollow noreferrer">https://www.biostars.org/p/428314/</a></p>

<p>It was missing the param <code>--simu-causal-loci</code>. </p>

<p>I created the <code>causal.snplist</code> file by finding out which SNP's are known causals of the treat I want to simulate.
In my case, I want to simulate a Diabetes phenotype, thus I:</p>

<ol>
<li>Got the known Diabetes causal SNP's from <a href="https://www.snpedia.com/index.php/Type-2_diabetes" rel="nofollow noreferrer">snpedia</a></li>
<li>Filtered out whichcausal SNP's also exist in my genomic data:</li>
</ol>

<pre><code>$ cat chr3_6_10.biallelic-only.bim | grep "rs4655595\|rs6718526\|rs4402960...
</code></pre>

<ol start="3">
<li>Created the <code>causal.snplist</code> with the causal SNP's as per <a href="https://cnsgenomics.com/software/gcta/#GWASSimulation" rel="nofollow noreferrer">documentation</a> </li>
</ol>

<pre><code>$ head causal.snplist
rs1111875
rs12255372
rs1801282
rs237025
...
</code></pre>

<ol start="4">
<li>Run gcta-simu again:</li>
</ol>

<pre><code>$ ./gcta64 --bfile chr3_6_10.biallelic-only --simu-cc 500 500 --simu-causal-loci causal.snplist --simu-hsq 0.5 --simu-k 0.1 --simu-rep 3 --out chr3_6_10.biallelic-only.gcta-simu
</code></pre>

<ol start="5">
<li>Got the expected results:</li>
</ol>

<pre><code>$ head chr3_6_10.biallelic-only.gcta-simu.phen 
0 HG00096 1 1 1 
0 HG00100 1 1 1 
0 HG00101 2 1 2 
0 HG00102 1 1 2 
0 HG00103 1 1 1
</code></pre>

<blockquote>
  <p>The last 3 columns are phenotypes. 3 phenotypes were generated due the param <code>--simu-rep 3</code>.</p>
</blockquote>

CC BY-SA 4.0
2020-04-23T17:58:13.167Z
Thanks for posting the answer to your own question, I was looking for something like this
Geraldine_VdAuwera
CC BY-SA 4.0
2020-03-23T11:13:22.623Z
2020-03-24T08:01:13.890Z
2020-03-24T08:01:13.890Z
Bruno Ambrozio
<p>I'm trying to simulate binary phenotypes from the <a href="https://bioinformatics.stackexchange.com/questions/10731/simulating-phenotype-with-the-1000-genomes-project">1000 Genome Phase 3 datasets</a> using <a href="https://www.biostars.org/p/428314/" rel="nofollow noreferrer">gcta64 --simu-cc</a>, but no success. 
Everything seems to be going well, but in the end I get:</p>

<pre><code>Error: can not open the file [] to read.
An error occurs, please check the options or data
</code></pre>

<p>And the log shows:</p>

<pre><code>Accepted options:
</code></pre>

<p>Here's the commands I'm using:</p>

<pre><code># Convert the VCF to plink format:
$ ./plink2 --vcf ../../ALL.phase3.biallelic-only.vcf.gz.10kSNPs.vcf.gz --make-bed --out ALL.phase3.biallelic-only.vcf.gz.10kSNPs

# Try to simulate the phenotype:
$ ./gcta64 --bfile ALL.phase3.biallelic-only.vcf.gz.10kSNPs --simu-cc 500 500 --simu-hsq 0.5 --simu-k 0.1 --simu-rep 3 --out ALL.phase3.biallelic-only.vcf.gz.10kSNPs
</code></pre>

<p>Here's the whole steps with the outputs:</p>

<pre><code>$ ls
gcta64  plink2

$ ./plink2 --vcf ../../ALL.phase3.biallelic-only.vcf.gz.10kSNPs.vcf.gz --make-bed --out ALL.phase3.biallelic-only.vcf.gz.10kSNPs
PLINK v2.00a2.3 64-bit (24 Jan 2020)           www.cog-genomics.org/plink/2.0/
(C) 2005-2020 Shaun Purcell, Christopher Chang   GNU General Public License v3
Logging to ALL.phase3.biallelic-only.vcf.gz.10kSNPs.log.
Options in effect:
  --make-bed
  --out ALL.phase3.biallelic-only.vcf.gz.10kSNPs
  --vcf ../../ALL.phase3.biallelic-only.vcf.gz.10kSNPs.vcf.gz

Start time: Sun Mar 22 11:56:23 2020
16384 MiB RAM detected; reserving 8192 MiB for main workspace.
Using up to 8 compute threads.
--vcf: 220000 variants scanned.
--vcf: ALL.phase3.biallelic-only.vcf.gz.10kSNPs-temporary.pgen +
ALL.phase3.biallelic-only.vcf.gz.10kSNPs-temporary.pvar +
ALL.phase3.biallelic-only.vcf.gz.10kSNPs-temporary.psam written.
2504 samples (0 females, 0 males, 2504 ambiguous; 2504 founders) loaded from
ALL.phase3.biallelic-only.vcf.gz.10kSNPs-temporary.psam.
220000 variants loaded from
ALL.phase3.biallelic-only.vcf.gz.10kSNPs-temporary.pvar.
Note: No phenotype data present.
Writing ALL.phase3.biallelic-only.vcf.gz.10kSNPs.fam ... done.
Writing ALL.phase3.biallelic-only.vcf.gz.10kSNPs.bim ... done.
Writing ALL.phase3.biallelic-only.vcf.gz.10kSNPs.bed ... done.
End time: Sun Mar 22 11:56:28 2020

$ ls
ALL.phase3.biallelic-only.vcf.gz.10kSNPs.bed    ALL.phase3.biallelic-only.vcf.gz.10kSNPs.fam    gcta64
ALL.phase3.biallelic-only.vcf.gz.10kSNPs.bim    ALL.phase3.biallelic-only.vcf.gz.10kSNPs.log    plink2

$ ./gcta64 --bfile ALL.phase3.biallelic-only.vcf.gz.10kSNPs --simu-cc 500 500 --simu-hsq 0.5 --simu-k 0.1 --simu-rep 3 --out ALL.phase3.biallelic-only.vcf.gz.10kSNPs
*******************************************************************
* Genome-wide Complex Trait Analysis (GCTA)
* version 1.93.0 beta Mac
* (C) 2010-2019, The University of Queensland
* Please report bugs to Jian Yang &lt;jian.yang@uq.edu.au&gt;
*******************************************************************
Analysis started at 11:59:16 GMT on Sun Mar 22 2020.
Hostname: Brunos-MBP

Accepted options:
--bfile ALL.phase3.biallelic-only.vcf.gz.10kSNPs
--simu-cc 500 500
--simu-hsq 0.5
--simu-k 0.1
--simu-rep 3
--out ALL.phase3.biallelic-only.vcf.gz.10kSNPs


Reading PLINK FAM file from [ALL.phase3.biallelic-only.vcf.gz.10kSNPs.fam].
2504 individuals to be included from [ALL.phase3.biallelic-only.vcf.gz.10kSNPs.fam].
Reading PLINK BIM file from [ALL.phase3.biallelic-only.vcf.gz.10kSNPs.bim].
220000 SNPs to be included from [ALL.phase3.biallelic-only.vcf.gz.10kSNPs.bim].
Warning: Duplicated SNP ID "rs145607083" has been changed to "rs145607083_5264"
.Warning: Duplicated SNP ID "rs145607083" has been changed to "rs145607083_5265"
.Warning: Duplicated SNP ID "rs71955229" has been changed to "rs71955229_27061"
.Warning: Duplicated SNP ID "rs71955229" has been changed to "rs71955229_27062"
.Warning: Duplicated SNP ID "rs71589472" has been changed to "rs71589472_42505"
.Warning: Duplicated SNP ID "rs563156514" has been changed to "rs563156514_49111"
.Warning: Duplicated SNP ID "rs563156514" has been changed to "rs563156514_49112"
.Warning: Duplicated SNP ID "rs539504239" has been changed to "rs539504239_79196"
.Warning: Duplicated SNP ID "rs35739849" has been changed to "rs35739849_105514"
.Warning: Duplicated SNP ID "rs148795567" has been changed to "rs148795567_123134"
.Warning: Duplicated SNP ID "rs143101359" has been changed to "rs143101359_201815"
.Reading PLINK BED file from [ALL.phase3.biallelic-only.vcf.gz.10kSNPs.bed] in SNP-major format ...
Genotype data for 2504 individuals and 220000 SNPs to be included from [ALL.phase3.biallelic-only.vcf.gz.10kSNPs.bed].
Simulation parameters:
Number of simulation replicate(s) = 3 (Default = 1)
Heritability of liability = 0.5 (Default = 0.1)
Disease prevalence = 0.1 (Default = 0.1)
Number of cases = 500
Number of controls = 500

Error: can not open the file [] to read.
An error occurs, please check the options or data

$ head ALL.phase3.biallelic-only.vcf.gz.10kSNPs.log 
*******************************************************************
* Genome-wide Complex Trait Analysis (GCTA)
* version 1.93.0 beta Mac
* (C) 2010-2019, The University of Queensland
* Please report bugs to Jian Yang &lt;jian.yang@uq.edu.au&gt;
*******************************************************************
Analysis started at 11:59:16 GMT on Sun Mar 22 2020.
Hostname: Brunos-MBP

Accepted options:
</code></pre>

<p>I'm opened to use other tools if you have any recommendation. Not sure, but looks like Plink doesn't do that (you can simulate phenotype as long as you also simulate the genetic data as well...)</p>

<ul>
<li>PS 1: I managed to simulate it before as answered <a href="https://bioinformatics.stackexchange.com/questions/10731/simulating-phenotype-with-the-1000-genomes-project">here</a>, but I've just realised it doesn't generate reliable ratios (although the logic in place, phenotypes are still too aleatory assigned - too low precision, recall and f1 scores).</li>
<li>PS 2: Also asked in the <a href="https://www.biostars.org/p/428314/" rel="nofollow noreferrer">BioStars</a> forum</li>
</ul>

<plink><simulated-data>
How to simulate phenotype from real genetic data for GWAS purpose?
# How to simulate phenotype from real genetic data for GWAS purpose?

(Asked by: username_0 on 2020-03-22)

I'm trying to simulate binary phenotypes from the 1000 Genome Phase 3 datasets using gcta64 --simu-cc, but no success. 
Everything seems to be going well, but in the end I get:
Error: can not open the file [] to read.
An error occurs, please check the options or data

And the log shows:
Accepted options:

Here's the commands I'm using:
# Convert the VCF to plink format:
$ ./plink2 --vcf ../../ALL.phase3.biallelic-only.vcf.gz.10kSNPs.vcf.gz --make-bed --out ALL.phase3.biallelic-only.vcf.gz.10kSNPs

# Try to simulate the phenotype:
$ ./gcta64 --bfile ALL.phase3.biallelic-only.vcf.gz.10kSNPs --simu-cc 500 500 --simu-hsq 0.5 --simu-k 0.1 --simu-rep 3 --out ALL.phase3.biallelic-only.vcf.gz.10kSNPs

Here's the whole steps with the outputs:
$ ls
gcta64  plink2

$ ./plink2 --vcf ../../ALL.phase3.biallelic-only.vcf.gz.10kSNPs.vcf.gz --make-bed --out ALL.phase3.biallelic-only.vcf.gz.10kSNPs
PLINK v2.00a2.3 64-bit (24 Jan 2020)           www.cog-genomics.org/plink/2.0/
(C) 2005-2020 Shaun Purcell, Christopher Chang   GNU General Public License v3
Logging to ALL.phase3.biallelic-only.vcf.gz.10kSNPs.log.
Options in effect:
  --make-bed
  --out ALL.phase3.biallelic-only.vcf.gz.10kSNPs
  --vcf ../../ALL.phase3.biallelic-only.vcf.gz.10kSNPs.vcf.gz

Start time: Sun Mar 22 11:56:23 2020
16384 MiB RAM detected; reserving 8192 MiB for main workspace.
Using up to 8 compute threads.
--vcf: 220000 variants scanned.
--vcf: ALL.phase3.biallelic-only.vcf.gz.10kSNPs-temporary.pgen +
ALL.phase3.biallelic-only.vcf.gz.10kSNPs-temporary.pvar +
ALL.phase3.biallelic-only.vcf.gz.10kSNPs-temporary.psam written.
2504 samples (0 females, 0 males, 2504 ambiguous; 2504 founders) loaded from
ALL.phase3.biallelic-only.vcf.gz.10kSNPs-temporary.psam.
220000 variants loaded from
ALL.phase3.biallelic-only.vcf.gz.10kSNPs-temporary.pvar.
Note: No phenotype data present.
Writing ALL.phase3.biallelic-only.vcf.gz.10kSNPs.fam ... done.
Writing ALL.phase3.biallelic-only.vcf.gz.10kSNPs.bim ... done.
Writing ALL.phase3.biallelic-only.vcf.gz.10kSNPs.bed ... done.
End time: Sun Mar 22 11:56:28 2020

$ ls
ALL.phase3.biallelic-only.vcf.gz.10kSNPs.bed    ALL.phase3.biallelic-only.vcf.gz.10kSNPs.fam    gcta64
ALL.phase3.biallelic-only.vcf.gz.10kSNPs.bim    ALL.phase3.biallelic-only.vcf.gz.10kSNPs.log    plink2

$ ./gcta64 --bfile ALL.phase3.biallelic-only.vcf.gz.10kSNPs --simu-cc 500 500 --simu-hsq 0.5 --simu-k 0.1 --simu-rep 3 --out ALL.phase3.biallelic-only.vcf.gz.10kSNPs
*******************************************************************
* Genome-wide Complex Trait Analysis (GCTA)
* version 1.93.0 beta Mac
* (C) 2010-2019, The University of Queensland
* Please report bugs to Jian Yang 
*******************************************************************
Analysis started at 11:59:16 GMT on Sun Mar 22 2020.
Hostname: Brunos-MBP

Accepted options:
--bfile ALL.phase3.biallelic-only.vcf.gz.10kSNPs
--simu-cc 500 500
--simu-hsq 0.5
--simu-k 0.1
--simu-rep 3
--out ALL.phase3.biallelic-only.vcf.gz.10kSNPs


Reading PLINK FAM file from [ALL.phase3.biallelic-only.vcf.gz.10kSNPs.fam].
2504 individuals to be included from [ALL.phase3.biallelic-only.vcf.gz.10kSNPs.fam].
Reading PLINK BIM file from [ALL.phase3.biallelic-only.vcf.gz.10kSNPs.bim].
220000 SNPs to be included from [ALL.phase3.biallelic-only.vcf.gz.10kSNPs.bim].
Warning: Duplicated SNP ID "rs145607083" has been changed to "rs145607083_5264"
.Warning: Duplicated SNP ID "rs145607083" has been changed to "rs145607083_5265"
.Warning: Duplicated SNP ID "rs71955229" has been changed to "rs71955229_27061"
.Warning: Duplicated SNP ID "rs71955229" has been changed to "rs71955229_27062"
.Warning: Duplicated SNP ID "rs71589472" has been changed to "rs71589472_42505"
.Warning: Duplicated SNP ID "rs563156514" has been changed to "rs563156514_49111"
.Warning: Duplicated SNP ID "rs563156514" has been changed to "rs563156514_49112"
.Warning: Duplicated SNP ID "rs539504239" has been changed to "rs539504239_79196"
.Warning: Duplicated SNP ID "rs35739849" has been changed to "rs35739849_105514"
.Warning: Duplicated SNP ID "rs148795567" has been changed to "rs148795567_123134"
.Warning: Duplicated SNP ID "rs143101359" has been changed to "rs143101359_201815"
.Reading PLINK BED file from [ALL.phase3.biallelic-only.vcf.gz.10kSNPs.bed] in SNP-major format ...
Genotype data for 2504 individuals and 220000 SNPs to be included from [ALL.phase3.biallelic-only.vcf.gz.10kSNPs.bed].
Simulation parameters:
Number of simulation replicate(s) = 3 (Default = 1)
Heritability of liability = 0.5 (Default = 0.1)
Disease prevalence = 0.1 (Default = 0.1)
Number of cases = 500
Number of controls = 500

Error: can not open the file [] to read.
An error occurs, please check the options or data

$ head ALL.phase3.biallelic-only.vcf.gz.10kSNPs.log 
*******************************************************************
* Genome-wide Complex Trait Analysis (GCTA)
* version 1.93.0 beta Mac
* (C) 2010-2019, The University of Queensland
* Please report bugs to Jian Yang 
*******************************************************************
Analysis started at 11:59:16 GMT on Sun Mar 22 2020.
Hostname: Brunos-MBP

Accepted options:

I'm opened to use other tools if you have any recommendation. Not sure, but looks like Plink doesn't do that (you can simulate phenotype as long as you also simulate the genetic data as well...)

PS 1: I managed to simulate it before as answered here, but I've just realised it doesn't generate reliable ratios (although the logic in place, phenotypes are still too aleatory assigned - too low precision, recall and f1 scores).
PS 2: Also asked in the BioStars forum

**Tags:** plink, simulated-data

---

## 1 answers

### Answer by username_0 on 2020-03-23. Score: 1 | Accepted answer

The question has been answered in the bioStars forum: https://www.biostars.org/p/428314/
It was missing the param --simu-causal-loci. 
I created the causal.snplist file by finding out which SNP's are known causals of the treat I want to simulate.
In my case, I want to simulate a Diabetes phenotype, thus I:

Got the known Diabetes causal SNP's from snpedia
Filtered out whichcausal SNP's also exist in my genomic data:

$ cat chr3_6_10.biallelic-only.bim | grep "rs4655595\|rs6718526\|rs4402960...


Created the causal.snplist with the causal SNP's as per documentation 

$ head causal.snplist
rs1111875
rs12255372
rs1801282
rs237025
...


Run gcta-simu again:

$ ./gcta64 --bfile chr3_6_10.biallelic-only --simu-cc 500 500 --simu-causal-loci causal.snplist --simu-hsq 0.5 --simu-k 0.1 --simu-rep 3 --out chr3_6_10.biallelic-only.gcta-simu


Got the expected results:

$ head chr3_6_10.biallelic-only.gcta-simu.phen 
0 HG00096 1 1 1 
0 HG00100 1 1 1 
0 HG00101 2 1 2 
0 HG00102 1 1 2 
0 HG00103 1 1 1


The last 3 columns are phenotypes. 3 phenotypes were generated due the param --simu-rep 3.

> **Comments:**
> **username_1**: Thanks for posting the answer to your own question, I was looking for something like this  

---

