Twenty-one of the cis-eQTL eGenes identified in fetal brain are located within a region of chromosome 17q21.31 containing a common 900-kb inversion polymorphism and several common duplications [22, 23]. Variants within this inversion (denoted “H2”), which appears to be under positive selection in Europeans [22], have recently been implicated in neuroticism [24–26], while markers on the non-inverted form (denoted “H1”) are associated with several neurodegenerative diseases [27–29]. For 13 of the eGenes in this region (e.g., KANSL1, LRRC37A, DND1P1), cis-eQTL could be largely explained by inversion status (r2 with H1/H2 tag SNP rs1800547 > 0.9), with variants tagging the inverted H2 form associated with both increases and decreases in gene expression (Table 1). For other genes in the region (e.g., NSF, ARL17A, ARL17B), identified cis-eQTL might index duplicated expressed gene sequence as well as regulatory variants that have arisen independently on the H1 or H2 haplotypes.Table 1Fetal brain eGenes located at a common inversion polymorphism on chromosome 17q21eGeneENSEMBL IDNumber eQTL SNPs FDR < 0.05Top eQTLTop eQTLFDRr2 with inversion*H1/H2 expression ratio NSF ENSG0000007396940rs38749434.05E−060.141.02 KANSL1 ENSG000001200712226rs26686902.81E−140.940.89 LRRC37A ENSG000001766812225rs37858845.89E−170.970.80 ARL17A ENSG0000018582934rs18631157.03E−040.111.00 KANSL1-AS1 ENSG000002144012215rs620571511.72E−110.940.81
