Figure 2

Genotypic frequency distribution for pairs of single nucleotide polymorphisms (SNPs) contributing to interaction effects and assessed by the Cochran–Mantel–Haenszel test. Significant interaction effects involve markers in the LPHN3 gene and a region in 11q that harbors the NCAM1 and DRD2 genes. Epistatic effects are depicted by changes in color that represent significant differences in genotypic distribution among severe (cases) vs not severe (controls) individuals. In there, the genotypes for one marker are held fixed whereas genotypes on the other marker vary. Inattention: (a) markers rs1947275 harbored in LPHN3 and rs17596017, in NCAM1, contribute to the severity of symptoms in this domain (M²=33.163, FDR-corrected P-value <0.001); (b) markers rs1947275 harbored in LPHN3 and rs12799083, in DRD2, produce a significant interacting effect contributing to the severity of symptoms (M²=28.456, FDR-corrected P-value <0.005). H/I: (c) markers rs35106420, in LPHN3, and rs620291, in NCAM1, produce an interacting effect contributing to the severity of symptoms (M²=20.497, FDR-corrected^* P-value <0.05). ODD: (d) markers rs995447, in LPHN3, and rs11214505, in NCAM1, interact to modify the severity of symptoms (M²=41.379, FDR-corrected P-value <0.0001); (e) rs734644, in LPHN3, and rs4938006 produce an epistatic effect contributing to the severity of symptoms (M²=26.795, FDR-corrected P-value <0.01). A/D: (f) markers rs1510920, in LPHN3, and rs4938006 localized closest to NCAM1 in an intragenic region of chromosome 11q, interact to modify the severity of symptoms (M²=41.379, FDR-corrected P-value <0.0001). ^*FDR-corrected P-values calculated on the basis of 567 independent tests, corresponding to the maximum number of SNP pairs for each of the four domains of the VAS-P questionnaire from which the severity of symptoms was derived. Abbreviations as in Figure 1.