Our previous research involving 167 nuclear families from the Autism Genetic Resource Exchange (AGRE) demonstrated that two intronic SNPs, rs1861972 and rs1861973, in the homeodomain transcription factor gene ENGRAILED 2 (EN2) are significantly associated with autism spectrum disorder (ASD).
The haplotype A-C of rs1861972 and rs1861973 is the core element of the observed haplotype association in this study, which plays a role as a protective factor against autism; in addition, the haplotype G-A-C is less frequent in male cases compared to controls (38.64 vs. 52.51%), which plausibly modulate disease vulnerability to autism.
Two intronic SNPs (rs1861972 and rs1861973) demonstrated significant association with autism (rs1861972, P=0.0018; rs1861973, P=0.0003; haplotype, P=0.000005).
While Del-T haplotype formed from rs34808376-rs1861973 markers showed increased non-transmission, the Ins-C showed significant transmission suggesting protective effect and risk, respectively, conferred by these haplotypes in autism etiology.