We observed important sex and developmental effects in the association of two individual genome-wide significant SCZ risk loci with high-alpha coherence; effects of intergenic chromosome 2 variant rs59979824 were observed among males 14–24, whereas the effect of GALNT10 variant rs11740474 on chromosome 5 was most robustly observed after age 25. rs59979824 has been associated with SCZ in three independent studies32,58,59 and a fourth study that examined overlapping SCZ and autism spectrum disorder (ASD) GWAS variants60. There is some evidence, albeit weak, from the Braineac database (http://www.braineac.org/) that rs59979824 is associated with the expression of TMEFF2, which has also been previously associated with SCZ61,62. Recent investigations have suggested that TMEFF2 may modulate the level of sarcosine (N-methylglycine) and therefore the activity of the glycine transporter type I (GlyT1)61,62. One of the two primary pharmacological possibilities for enhancing function of the NMDA receptor relies on inhibiting the glycine transporter type I (GlyT-1) with sarcosine, bitopertin (RG1678), or ALX-540763. Sarcosine has shown promising early results in ameliorating cognitive and negative symptoms in SCZ. GALNT10 variant rs11740474 has also been implicated in several previous studies of SCZ32,58,59,64 and one study of ASD60.
