There are currently hundreds of genetic variants associated with schizophrenia (SZ) through genome-wide association (Buniello et al., 2019) such that it is critical to consider SZ risk genetics in the context of brain developmental and mature functional properties as well as in molecular signaling pathways. One putative risk allele has been identified in the 3′ untranslated region of claudin-5 (CLDN5 (Greene et al., 2018);), a tight junction protein that contributes to blood-brain barrier (BBB) integrity (Abbott et al., 2006). CLDN5 is located in the region of hemizygous deletion in the 22q11. 2 deletion syndrome (22qDS). SZ risk is greatly elevated in 22qDS; with most studies finding this risk increases roughly 25-fold to at least 25%(Gothelf et al., 1999; Hoeffding et al., 2017; Murphy et al., 1999; Schneider et al., 2014; Van et al., 2017) and see Vangkilde et al.(2016). The CLDN5 variant rs10314 was associated with decreased claudin-5 expression, and was present in the remaining 22q11. 2 region in 9 of 15 22qDS subjects with SZ, but only 8 of 44 22qDS subjects without SZ (X2 P< 0.04)(Greene et al., 2018).

To determine whether this association stands with an independent and larger sample, we evaluated whole genome sequencing data of 490 22qDS patients from the 22q11 International Brain and Behavior Consortium (22q11-IBBC (Mlynarski et al., 2016);) aligned to Hg38. Genotyping at the CLDN5 variant site had high depth (17.4 X in average). As expected no heterozygosity was detected within the 22q11. 2 deleted region.