Sea of genomic wide significant hits in GWAS (Plink2) and Absence when using regenie

Question

[a.papadam]

Hi all,

I recently performed a GWAS on a continuous measurement (the previous GWAS used a relative binary measurement), but when I run PLINK2, it returns thousands of genome-wide hits without forming any clear peaks. In contrast, when I use REGENIE, there are no significant hits.

This could be due to noise, a confounder, or a genuinely polygenic signal with subtle effects.

However, I am unsure how to test each scenario and correct for it if possible. I have tried various covariates in my GWAS, different scaling methods, excluding outliers, etc.

Any insights?

Thanks in advance.

[Corentin]

Hi,

It would be useful to know the commands you used to perform these association tests.

The first thing that comes to mind is that the p-values from PLINK are not corrected for multiple testing. So, your "significant hits" will become not-significant after you correct them for the number of tests you are doing. (see "Basic multiple testing correction" at https://www.cog-genomics.org/plink/2.0/assoc).

Also, if you have some family structure in your dataset, a mixed-model (eg: regenie) can account for that, but not PLINK.