I'm hiring a computational biologist interested in complex trait genetics using deep learning approaches. Reach out to me, if interested.

Need a break from doomscrolling?

Do you study the genetics of disease subtypes? Have you ever wondered how to efficiently run gene-based associations with multicategorical outcomes? Join us for the IGES Journal Club on Wednesday, February 26, 2025! 11AM ET.

Back to the effect of precision
Precision of prediction improves power, or equivalently prediction error reduces power but doesn’t increase inflation under the null

How well does your formula work under the alternative with finite N?

Pretty well

What happens under the alternative?

See figure for formula under the alternative

τ2 is the precision of the prediction

Can you estimate Φ?

Yes

See figure: most of the Φ are around 10e-5

Does it matter for TWAS in practice?

Yes

See inflation in figure when using UK Biobank genotype data and null traits Y. It will continue growing as N grows.

How we does your formula match with finite N?

Quite well

Does prediction error drive inflation?

No, it’s not the prediction error

See figure Eχ2 does not depend on the precision consistent with established error in variable literature

It’s the polygenicity of Y since Eχ2 = 1 + N h2 Φ. The inflation is 0 when the polygenic component of Y = 0

Does this matter?

Yes

See example in figure 1, pink area is much larger than the negligible blue area in this example

Under the null, the Eχ2 should be 1, but it’s larger than 1 when Y is polygenic

Yes

TWAS yields inflated p-values when the target trait is polygenic