Extended Data Fig. 9: Exploring prenatal factors that may influence risk of neurodevelopmental conditions.
From: Examining the role of common variants in rare neurodevelopmental conditions
(A) Points show genetic correlations between neurodevelopmental conditions and prenatal risk factors, before and after conditioning on educational attainment or cognitive performance. Genetic correlations with our GWAS meta-analysis for neurodevelopmental conditions were estimated using Linkage Disequilibrium Score Regression. Those conditioned on the GWAS summary statistics for educational attainment or cognitive performance were estimated using GenomicSEM. See Supplementary Table 11 for exact estimates of genetic correlations and two-sided P values. (B) Percentage of the genetic correlation between neurodevelopmental conditions and prenatal risk factors that is explained by the latent educational attainment (EA) variable estimated using GenomicSEM (red bars and percentage written in text). Green bars indicate the contribution from the non-EA latent variable. The estimates are standardized so that the total height represents the genetic correlation between neurodevelopmental conditions and prenatal risk factors. (C) Percentage of the genetic correlation between neurodevelopmental conditions and prenatal risk factors that is explained by the latent cognitive (Cog) variable (red bars and percentage written in text). Green bars indicate the contribution from the non-cognitive (Non-Cog) variable. In (B) and (C), we focused on prenatal factors that showed significant genetic correlations with neurodevelopmental conditions. (D) Association between PGSs and prematurity, a risk factor for neurodevelopmental conditions. Points show the differences in PGSs between premature and term probands, estimated in DDD using linear regression models. See Supplementary Table 8 for exact two-sided P values and sample sizes. Note that for PGSNDC,DDD, probands who were included in the GWAS were not tested, which left 703 probands, of which 83 were born prematurely. A negative estimate indicates that probands who were born prematurely had a lower polygenic score than term probands, or their parents had a lower polygenic score than the parents of term probands. Associations that pass Bonferroni correction for five traits in (A) or five polygenic scores in (B) are indicated by a double asterisk and nominally significant (P < 0.05) results by one asterisk. Error bars show 95% confidence intervals.
