Analyses of inversion polymorphisms

Two genome-wide significant SNPs for the neuroticism analysis are located within well-known inversion polymorphisms, on chromosomes 8 and 17. Using the genotypic data available for UKB participants, we called the inversion genotypes for UKB participants using a PCA-mixture method. For both inversions, the method clearly distinguishes 3 clusters of genotypes, corresponding to inversion genotypes (Supplementary Fig. 10). We validated the PCA-mixture procedure using existing methods designed to call inversion genotypes³⁹ (Supplementary Table 26).

For both inversions, we established that the inversion-tagging SNPs were always located in close proximity of the inversion region (Fig. 3b and Supplementary Figs. 10–11). Supplementary Tables 27–28 list the twenty variants that most strongly correlate with the PCs that capture the inversion polymorphisms on chromosome 8 and 17, respectively. In additional analyses, we confirmed that the inversion is associated with neuroticism and subjective well-being in independent cohorts (Supplementary Tables 29–30 and Supplementary Fig. 12–13).