PolyFun avoids directly estimating the proportionality factor 1/var[βi|βi ≠ 0] by constraining the prior causal probabilities P(βi ≠ 0|ai) in each tested locus to sum to 1.0. This constraints implies that each locus is a-priori expected to harbor one causal SNP, consistent with previous fine-mapping methods5,6,22 (this constraint is ignored by PolyFun + SuSiE because it is invariant to scaling of prior causal probabilities). Hence, the main challenge is estimating the per-SNP heritabilities var[βi|ai].
