Table 1.
Prioritization and scoring algorithm rules (details are given in Supplementary Table 2) for SNPs selected with P < 0.001 in the family-based GWA and P < 0.05 in the siblings case-control studies performed in the discovery sample.
| General principle | Points | Example |
|---|---|---|
| Statistical parameters (max 2 points) | ||
| P-value of the association of the SNP with autism in GWAS is <10−8 vs. between 10−8 and 10−5. | 1 vs. 0.5 | None* vs. rs7974275 (GRIN2B) |
| Odds ratio associated with the risk-associated allele of the SNP is ≥1.5 in the sibling case-control study. | 1 | rs4251859 (PLAUR) |
| Genomic characteristics (max 2 points) | ||
| The SNP is located within the gene (including 5 kb upstream and downstream regions). | 1 | rs2770298 (HTR2A) |
| The SNP acts as an eQTL of the gene as determined by two eQTL databases, “Genevar” (Yang et al., 2010) and “eQTL resource @ Pritchard's lab” (eqtl.uchicago.edu) (Veyrieras et al., 2008; Degner et al., 2009; Pickrell et al., 2010). | 1 | rs2297389 (GABRR1) |
| Previous reporting (max 1 point) | ||
| The gene has been associated through genome-wide or gene candidate association studies, mutations, or structural abnormalities with autism vs. with a related neurodevelopmental genetic disorder (e.g., schizophrenia, bipolar, mental retardation). | 1 vs. 0.5 | rs3928471 (SLC9A9) vsrs72723811 (NRG1) |
| Physiological properties (max 4 points) | ||
| The expression of the gene is significantly different in patients with autism compared with controls in brain (Purcell et al., 2001; Garbett et al., 2008) or in lymphoblastoid cell lines (Gregg et al., 2008; Hu et al., 2011). | 1 vs. 0.5 | rs3928471 (SLC9A9) vs. rs636624 (PTPRG) |
| The gene has a specific role or restricted expression in the CNS. | 1 | rs12514116 (KCNIP1) |
| A mouse model exhibits either impairment of CNS development or function with or without an autism-related behavior as reported in the mouse gene informatics database from the JAX laboratory (Blake et al., 2011) and literature. | 1 | rs314253 (DLG4) |
| The gene is a part of a pathway in which other genes have been strongly associated with autism (development of the CNS, neurogenesis, neuronal migration, neuron projection, synaptogenesis, synaptic transmission) or is a part of a biochemical pathway from in which other genes have been strongly associated with autism (e.g., TSC/mTOR, MET receptor tyrosine kinase pathways). | 1 | rs9940922 (CDH13) |