Extended Data Fig. 8: Exploring sex differences in polygenic risk.
From: Examining the role of common variants in rare neurodevelopmental conditions
A) Comparison of polygenic scores between undiagnosed male and female probands in DDD and GEL combined. We used all undiagnosed probands with neurodevelopmental conditions regardless of trio status in this analysis (N = 1,426 females and N = 2,427 males in DDD; N = 112 females and N = 146 males in DDD excluding GWAS samples; N = 918 females and N = 1,574 males in GEL). Square points show the differences in average polygenic scores between female and male probands. A positive difference indicates that female probands have higher PGS than male probands. B) Comparison of polygenic scores between unaffected mothers and fathers of undiagnosed probands from a combined sample of 1,523 trios and 1,343 trios from DDD and GEL, respectively. Triangles show the differences in average polygenic scores between mothers and fathers. A positive difference indicates that mothers have higher PGS than fathers. Two-sided t-tests were used to compare average PGSs in A) and B). C) pTDT results in undiagnosed female and male probands with unaffected parents (N = 586 females and N = 937 males in DDD; N = 99 females and N = 125 males in DDD excluding GWAS samples; N = 490 females and N = 853 males in GEL). We tested if probands’ polygenic scores deviated from the mean parental polygenic scores using two-sided one-sample t-tests. Points show the mean pTDT deviation (difference between the child’s polygenic score and the mean parental polygenic score, in units of the s.d. of the latter). Error bars show 95% confidence intervals. The significant result that passes Bonferroni correction of five tests is highlighted by a double asterisk. See Supplementary Table 9 for results of pTDT.
