Table 2.

List of top variants annotated to the five presynaptic assembly genes enriched in the European GWAS of BIS in JME (n = 324).

Gene	Location	Size	rsid	Beta	P value	PVE
PTPRD	chr9:8,314,246–10,613,002	2,298,757	rs1781264	1.827	1.19E-04	0.042
NLGN1	chr3:173,398,448–174,286,644	888,197	rs73177088	6.191	9.95E-04	0.044
NLGN4X	chrX:5,890,042–6,228,867	338,826	rs146813567	−2.898	3.06E-04	0.039
IL1RAPL1	chrX:28,587,446–29,956,718	1,369,273	rs5943492	1.039	8.73E-04	0.043
PTEN	chr10:87,862,563–87,971,930	109,368	rs112050451	5.158	1.27E-03	0.041

Variants with P ≤ 5 × 10⁻⁴ were annotated to the gene with the nearest transcription start site using the Ensembl Variant Effect Predictor (v94)⁶². This gene set was used as input in a GO enrichment analysis^63,64, to test for enrichment in annotated pathways. One-sided hypergeometric tests were completed to identify over-representation of pathways⁴². To reduce the risk of false positive results, a permutation procedure⁶⁵ was employed by randomly shuffling GWAS p values 2000 times, each time re-applying the P ≤ 5 × 10⁻⁴ threshold and calculating the hypergeometric test statistics. For each pathway, the final permutation-based p value was calculated as the percentage of the 2000 permutations that produced a p value less than or equal to the p value calculated from the non-permuted data. A pseudo count was added during this calculation to prevent calculating p values equal to 0.

PTPRD, Protein Tyrosine Phosphatase Receptor Type D; NLGN1, Neuroligin 1; NLGN4X, Neuroligin 4 X-Linked; IL1RAPL1, Interleukin 1 Receptor Accessory Protein Like 1; PTEN, Phosphatase and Tensin Homologue.