<p>Hi,</p>

<p>This is a pretty general question I know, but I'm wondering why I might be seeing a statistically significant peak from a GWAS in one population and nothing in another. Statistical power to detect an association is roughly the same in both populations.</p>

<p>Hope somebody can give me some insight.</p>

<p>Sally.</p>

<ul>
<li>
<p>The locus is real, but only has an effect in one population. You could hypothesize that this is due to interaction with other alleles associated with that population, or due to an environmental difference between the populations, or due to differences in the condition. This has been seen several times (though no one has adequate explanation that I'm aware of) in common diseases such as various cancers. Alternately, the effect is real in both populations but the effect is so modest that other environmental or genetic factors hide the signal in one population. That's a different situation from true interaction.</p>
</li>
<li>
<p>The locus, despite apparent statistical significance, is in fact only appearing by chance. That's why you need replication for these studies.</p>
</li>
<li>
<p>There is a systematic difference in genotyping technique between populations, e.g. different platforms, different DNA extraction methods, hybridization at different genome cores, etc. This difference is affecting this locus, either creating a new signal or removing one selectively.</p>
</li>
<li>
<p>The significant probe is flawed somehow: it cross-hybridizes, it has weak signal that is noisy, etc. This gives a false positive result in one population.</p>
</li>
</ul>
<p>Have a look at the raw genotype data to see if the calls are credible in both populations. Look for biases associated with population. Look for systematic clinical/macroscopic differences in your phenotype between populations For example, if this were breast cancer, is one population African-derived and another European-derived? If so, not only do you have different allele frequencies as Jorge points out, you also have different predispositions to ER-positive vs ER-negative cancer (probably due in part to the genetic architecture, but also due to environmental differences). If both populations were Caucasian, is there an ascertainment bias due to different medical systems diagnosing patients differently? Etc...</p>