GWAS power estimate for a single factor mediating the FPE. (A) In females exposed to high ASD risk, the protective factor will be enriched in unaffected individuals (green) and largely absent in cases (purple). We estimate a distinct difference in the frequency of the protective allele in these two cohorts (Additional file 1: Supplementary Methods) for an analysis based only on females (red line). Conversely, the protective allele has no effect in males and will be observed at an equal frequency in male cases and controls. Including males in a GWAS analysis will therefore add noise (blue line, representing the observed 5.25:1 ratio of males to females in Anney et al. ) resulting in a reduction in power. (B) An estimate of GWAS power to detect a single FPE allele in females only (red) and females and males (blue) under a model where protection contributes 50% of the observed 5.25:1 sex bias. The vertical lines represent the sample size in this study (red) and the Anney et al.  GWAS study (blue).