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Confounding Factors In Gwas

Good morning,

I would like to ask a little question. I have to perform a GWAS. However, analyzing my data, I have found that there are 3 populations among my individuals and a lot of mestizos:

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Going on with the analysis, I find a lot of false positives (analyzing a quantitative trait). How to deal with mestizos in GWAS? Is it a confounding factor, right?

Thanks.

gwas
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updated by Philipp Bayer Philipp Bayer • written by int11ap1 int11ap1

1 answer

That depends on the statistical method and the software you want to use - if you like PLINK, you can try to run a linear regression using your 3 populations as covariates, as described here in the manual (scroll down to "Linear and logistic models"). This should give you substantially higher p-values, run the analysis with both covariates and without to see the difference.

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written by Philipp Bayer Philipp Bayer

I don't know how to create the covariate files...

• 0 views • link
written by int11ap1 int11ap1

The covariate file in PLINK looks like the phenotype file, here's a basic example with the covariates "AGE" and "ANCESTRY" and the family ID FAM001 and the individual IDs 1 and 2:

FID IID AGE ANCESTRY
FAM001 1 27 3
FAM001 2 35 1

If you save this as "file.txt" and add the covariates in PLINK using --covar file.txt it will use all of these, to restrict the covariates to for example "age" use --covar-name AGE

Source

• 146 views • link
written by Philipp Bayer Philipp Bayer

Are you sure it is a good idea to put the populations as covariates? Think that I have a lot of mestizos. Each of them has a different ancestral composition (0.2% of population 1, 0.5% of population 2, 0.3% of population 3). Their genotype may differ a lot even though having similar percentages for each population. So, I think that the only way to solve this is excluding mestizos.

• 0 views • link
written by int11ap1 int11ap1

If you think that you have subpopulations inside your mestizos, try using EIGENSTRAT instead to correct the alleles themselves for pop stratificiation, then you don't have to use the covariates.

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written by Philipp Bayer Philipp Bayer

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