Determining a SNP p-value Cutoff for GWAS
0
1
Entering edit mode
7.3 years ago

As a preamble, I am somewhat knowledgeable in statistics, but have reached a problem in that I'm not sure how to go about statistical significance in GWAS based on the literature alone (I've read a couple papers but it's a little dense given my limited skill set and I'm not sure how the numbers really line up in regard to the equations often posted).

Essentially I have 143 cell lines and 50,291 SNPs being investigated. I have read that you might take the alpha value of 0.05 and divide by the number of SNPs to use that as a cutoff (so in this case, 0.05 / 50,291 ~ 9.94x10^-7). Unfortunately that is a bit too strict given the 143 cell lines with genetic data I have available.

The statistical testing software I am using is providing a multivariate ANCOVA, controlling for biological sex, age, race, ethnicity, and family (these being covariates), with a single response variable (R1). My "main" regression model output statistic and p-value are based on Pillai's Trace. As stated above, 9.94x10^-7 is a bit too strict, given that my "best" p-values are around 1x10^-5. But should I be considering those significant at all? Why or why not? Are there steps in this process that I am completely forgoing?

Thank you so much!

genome SNP • 5.4k views
ADD COMMENT
0
Entering edit mode

Did you try calculating adjusted p-values using B-H or B-Y? I guess you can use adjusted p-values (BY or BH).

ADD REPLY
0
Entering edit mode

Is B-H referring to Benjamini-Hochberg and B-Y to Benjamini-Yekutieli? I haven't tried calculating them... So would I set my false positive rate as 10% (for B-H)? That would put one of my example "best" P-values at 1x10^-5

ADD REPLY
0
Entering edit mode

adjusted p-rate cutoff is 0.05 (in general). Some prefer 0.01. B-H and B-Y are as you mentioned above. You may use qvalue package in R.

ADD REPLY
0
Entering edit mode

Okay, totally just curious here... So say my raw p-value is 1x10^-5. So then I divide that by the number of SNPs (50,291) for my corrected p-value (Bonferroni), as ~1.988x10^-10. Then I use that as my p-value in the B-H procedure?

ADD REPLY
0
Entering edit mode

Yes, calculate the nominal p-value at which FDR is 5%, 1%, etc., and then use that as the cut-off.

Another thread to assist in linking these up:

ADD REPLY

Login before adding your answer.

Traffic: 1715 users visited in the last hour
Help About
FAQ
Access RSS
API
Stats

Use of this site constitutes acceptance of our User Agreement and Privacy Policy.

Powered by the version 2.3.6