Can rare variants fake common GWAS hits?

Collections of rare causal variants can create synthetic genome-wide association signals at common SNPs.

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What kind of GWAS signal can rare variants create?

Synthetic associations at common SNPs.

Assumed frequency range for modeled causal variants?

Between 0.005 and 0.02.

What happens as the disease class grows?

Collectively rare alleles approach creating detectable signals.

When is synthetic signaling prohibited?

When causal variants are so numerous they are roughly evenly distributed through the genealogy.

Why consider number and disease-class proportion separately?

Both shape whether rare variants generate synthetic signals.

Can signals combine across rare alleles?

Yes—signals can combine in the genealogy.

What classic GWAS assumption does this challenge?

That association implies a common causal variant of similar frequency.

Are individual rare alleles frequent?

No—each can be very low frequency yet still matter collectively.

Study style?

Simulation/theoretical population genetics of GWAS.

Student takeaway?

Interpret common GWAS hits with rare-variant synthetic explanations in mind.