Perhaps the most notable pattern that emerges from our biological analyses is that the inversions on chromosomes 8 and 17 are implicated consistently across all analyses. The inversion-tagging SNP on chromosome 8 is in LD with SNPs that have previously been found to be associated with BMI32 and triglycerides33 (Supplementary Table 22). We also conducted eQTL analyses in blood for the inversion itself and found that it is a significant cis-eQTL for 7 genes (Supplementary Table 24). As shown in Figure 4b, all 7 genes are positioned in close proximity to the inversion breakpoints, suggesting that the molecular mechanism underlying the inversion’s effect on neuroticism could involve the relocation of regulatory sequences. Two of the genes (MSRA, MTMR9) are known to be highly expressed in tissues and cell types that belong to the nervous system, and two (BLK, MFHAS1) in the immune system. In the tissue-specific analyses, we found that the SNP tagging the inversion is a significant eQTL for two genes, AF131215.9 (in tibial nerve and thyroid tissue analyses) and NEIL2 (tibial nerve tissue), both of which are also located near the inversion breakpoint.
