Previous studies indicate a link between an exceptionally long GA-repeat in the Zinc finger MYM-type containing 3 (ZMYM3) gene and higher-order brain functions, reflected in human-specific cognitive disorders. Here, we studied this GA-repeat in a cohort of unrelated male subjects, consisting of patients affected by autism spectrum disorder (ASD) (n = 100) and controls (n = 200). We also analyzed pooled samples from this study and previous studies of this GA-repeat in three other major psychiatric disorders (n = 721), including schizophrenia (SCZ), bipolar disorder (BD), and late-onset neurocognitive disorder (NCD) and pooled controls (n = 487). An allele at the extreme short end (17-repeat) was detected in the ASD cases, which was not detected in the control samples (mid-p ≤ 0.05). This allele overlapped with the extreme allele detected in SCZ, BD, and late-onset NCD. Furthermore, we found a significantly different genetic architecture at this locus in the ASD patients vs. pooled controls. In conclusion, we report a significant association between the human ZMYM3 17-repeat allele and ASD, which overlaps with SCZ, BD, and late-onset NCD. Our findings reinforce the hypothesis that low-frequency alleles at the extreme allele lengths at this locus co-occur with a number of major psychiatric disorders and undergo natural selection.
Razavi et al. (Fri,) studied this question.