Table 1.
Examples of HARs, VEs, and CNEs that have more variants found in cases compared to controls
| Element | Cohort | Variants found in cases and not controls | Number of cases with variants | Number of controls with variants | Potential target genes | Disease and functional associations |
|---|---|---|---|---|---|---|
| HAR1362 | NIMH | chr2:44721116 (G>A), chr2:44721350 (G>A) | 2 | 0 | CAMKMT, SIX3∗, PREPL | required for development of anterior neural structures (SIX3)71 |
| HAR1479 | NIMH | chr2:145978583 (G>A), chr2:145978593 (C>A) | 2 | 0 | ZEB2∗, GTDC1, ARHGAP15 | mutations cause Mowat-Wilson syndrome (ZEB2)72 |
| HAR3094 | NIMH | chrX:30389661 (G>A), chrX:30389670 (A>G) | 2 | 0 | NR0B1∗, CXorf21, IL1RAPL1∗, MAGEB1, MAGEB2, MAGEB3 | mutations associated with ASD and ID (IL1RAPL1)62,63 |
| HAR3134 | HMCA, NIMH | chrX:121796532 (T>C), chrX:121796545 (A>G) | 3 | 0 | GRIA3∗ | mutations associated with ASD, X-linked syndromic ID, and schizophrenia (GRIA3)60,61,73 |
| HAR3162 | NIMH | chrX:143707357 (G>C), chrX:143707386 (A>G), chrX:143707399 (G>A), chrX:143707479 (G>A) | 4 | 1 | SLITRK2, SLITRK4 | mutations associated with ID, DD, and neuropsychiatric symptoms (SLITRK2)66 |
| VE15 | NIMH | chr1:10797318 (T>C), chr1:10797401 (G>C) | 2 | 0 | CASZ1∗ | mutations associated with ASD, ID, and DD (CASZ1)74 |
| VE162 | NIMH | chr1:213598724 (T>C), chr1:213598876 (A>C) | 2 | 0 | PROX1∗, RPS6KC1, SMYD2 | regulates interneuron differentiation (PROX1)70 |
| VE235 | NIMH | chr2:63276286 (C>A) | 1 | 0 | OTX1∗ | mutations associated with ASD75 |
| VE462 | NIMH | chr3:147564829 (T>C), chr3:147564920 (T>C), chr3:147565003 (T>C) | 3 | 0 | ZIC1∗, ZIC4 | involved in medial telencephalon development (ZIC1)76 |
| VE644 | NIMH | chr5:87692588 (G>T), chr5:87692852 (C>T) | 2 | 0 | MEF2C∗, TMEM161B | mutations associated with ASD (MEF2C)65; mutations associated with polymicrogyria (TMEM161B)77,78 |
| CNE6445 | HMCA | chr17:67603809 (C>T) | 2 | 0 | KCNJ16, MAP2K6∗, KCNJ2 | member of MAP/ERK pathway, which has been linked to changes in social behavior (MAP2K6)79 |
| CNE7200 | HMCA | chrX:18442211 (T>C) | 2 | 0 | CDKL5∗ | mutations associated with Rett syndrome and epilepsy (CDKL5)80 |
A full list is in Table S4. Asterisks indicate genes that are loss-of-function intolerant (pLI > 0.9).35 Potential target genes were determined by gene proximity and by location within the same topologically associated domain.81,82 For HAR3162, one variant was observed in both a case and a control in HMCA and was excluded from the table. Coordinates are in hg19. ID, intellectual disability; DD, developmental disorder.