Selection of a "suggestive" level of association in a GWAS study

Question

[LauferVA]

In GWAS studies, 5 x 10^-8 seems the defacto standard for association. A lesser known threshhold is 1 x 10^-5.

This threshhold is often called "suggestive association."

I am writing to ask, where did this figure come from? Were empirical tests or statistical simulations done to select this level?

I can find many papers that USE this level, but far fewer that JUSTIFY it. Any relevant citations would be welcome, and thank you.

Answer 1

[lindsay.leek]

"The P values of Bonferroni corrected thresholds for suggestive, 5 and 1% genome-wide significant levels were 1, 0.05 and 0.01, respectively, divided by the number of SNPs used in the GWAS. The suggestive level was first proposed by Lander and Kruglyak [17] and represents the threshold where, under the null hypothesis, one false positive is expected per genome scan."

So the suggestive line is calculated as the -log10( 1 / number of variants)

Reference: Guo, Y., Huang, Y., Hou, L., Ma, J., Chen, C., Ai, H., ... & Ren, J. (2017). Genome-wide detection of genetic markers associated with growth and fatness in four pig populations using four approaches. Genetics Selection Evolution, 49(1), 21.

[LauferVA]

this is interesting - of course the bulk of the literature of which I am aware derives an understanding of these levels from the number of effectively independent markers.

so would be odd to use a pig based threshold unless they have similar levels of LD and numbers of haploblocks

[lindsay.leek]

Hi Vincent,

I added the paper because of " was first proposed by Lander and Kruglyak [17] " to indicate that they were the first to propose this. If you go to the paper of Lander Kruglyak, you will find a more precise explanation of the suggestive linkage. Good luck!

[LauferVA]

Thank you for clarifying, lindsay!