Table 3. Top candidate genes based on integrating a decade of genome-wide linkage and association studies, the autism male bias and differential expression in brain and blood of individuals with autism spectrum disorder (ASD).
|
Differential expression in blood |
Differential expression in brain |
|||||
|---|---|---|---|---|---|---|
| Gene | t-test P | FDR | t-test P | FDR | Male-specific genetic distance from marker (cM) | Association with disorders comorbid to ASDa |
| TRIM44 | 9.5e−02 | 4.8e−02 | 5.1e−03 | 1.4e−02 | 0.84 | |
| ITPR1 | 7.7e−01 | 9.3e−04 | 1.9e−03 | 1.5e−03 | 1.09 | 4, 7, 15, 16 |
| IREB2 | 2.3e−02 | 4.0e−02 | 1.2e−02 | 2.8e−03 | 1.39 | 4, 10 |
| CNTN4 | 1.4e−01 | 2.4e−02 | 3.2e−01 | 5.1e−03 | 1.88 | 4, 6, 8, 16, 18, 19 |
| NMNAT3 | 2.0e−01 | 4.5e−02 | 4.6e−01 | 8.3e−03 | 2.39 | 10 |
| RAB6B | 2.0e−01 | 4.5e−02 | 1.0e−03 | 1.9e−04 | 3.02 | |
| CADPS2 | 4.1e−04 | 3.7e−03 | 1.0e−05 | 4.9e−05 | 3.34 | 5, 6 |
| SPTBN1 | 1.5e−03 | 9.1e−03 | 1.6e−01 | 3.1e−06 | 3.56 | 1, 16 |
| TMEM108 | 2.1e−01 | 4.5e−02 | 1.0e−01 | 2.8e−03 | 4.09 | |
| ACPL2 | 8.3e−02 | 2.8e−02 | 8.2e−02 | 2.4e−03 | 4.43 | |
| ADCY2 | 1.4e−01 | 3.2e−02 | 3.9e−02 | 3.9e−03 | 4.77 | 16 |
| NSUN2 | 1.1e−02 | 1.1e−02 | 7.7e−01 | 3.8e−02 | 6.62 | 16 |
| PANK1 | 1.4e−02 | 3.8e−02 | 7.7e−03 | 2.8e−03 | 7.14 | |
| SUMF1 | 1.4e−01 | 2.4e−02 | 4.9e−01 | 6.7e−03 | 7.31 | 9, 10, 13, 21, 22 |
| TANC1 | 1.2e−01 | 1.7e−03 | 6.0e−02 | 3.8e−02 | 7.31 | 4, 6, 17, 19, 20 |
| SLC23A2 | 1.6e−02 | 2.7e−02 | 2.4e−02 | 1.8e−02 | 8.35 | |
| EPB41L5 | 2.5e−03 | 1.3e−02 | 3.5e−02 | 1.8e−02 | 8.65 | |
| ALKBH3 | 1.6e−01 | 3.7e−02 | 3.0e−05 | 2.4e−04 | 9.00 | |
| SLC9A9 | 7.5e−02 | 2.8e−02 | 4.3e−04 | 1.8e−04 | 9.04 | 5, 6, 8, 15, 18, 20 |
| NTRK3 | 3.0e−02 | 4.0e−02 | 7.9e−02 | 9.1e−03 | 9.67 | 2, 3, 5, 6, 7, 11, 15, 16, 17, 23 |
| PLSCR4 | 5.4e−02 | 2.8e−02 | 8.4e−03 | 5.0e−04 | 12.30 | 7, 16 |
| MYO10 | 1.4e−01 | 3.2e−02 | 1.4e−01 | 9.2e−03 | 12.64 | 10 |
| KCNMA1 | 1.3e−02 | 3.8e−02 | 2.4e−01 | 2.2e−02 | 13.86 | 2, 8, 10, 15, 16, 18 |
| SMYD3 | 4.8e−04 | 9.5e−03 | 2.6e−02 | 1.8e−03 | 14.32 | |
| ATP2B2 | 5.3e−02 | 2.4e−02 | 1.1e−03 | 9.4e−04 | 14.77 | 14, 16, 20 |
| ALDH18A1 | 9.1e−03 | 3.8e−02 | 6.0e−01 | 4.1e−02 | 15.93 | 8, 10, 12, 18, 19, 20 |
| LMCD1 | 1.3e−01 | 2.4e−02 | 5.4e−01 | 6.7e−03 | 16.72 | |
| ATG7 | 2.7e−01 | 4.5e−04 | 3.4e−04 | 7.1e−04 | 16.78 | 10 |
| SYN2 | 2.6e−01 | 2.6e−02 | 4.6e−03 | 2.9e−03 | 18.41 | 7, 8, 15, 16 |
| MKRN2 | 2.3e−01 | 2.6e−02 | 2.0e−02 | 9.5e−03 | 18.70 | |
Abbreviation: FDR, false discovery rate.
Listed are genes located within 20 male-specific cM of genome-wide significant autism markers, which are also differentially expressed in both brain and blood of individuals with ASD. Of these, 19 genes (63%) were previously implicated in neurological disorders with high degrees of overlap in symptomatology and morbidity to ASD.
List of disorders: (1) neurofibromatosis, (2) tuberous sclerosis, (3) anxiety disorders, (4) ataxia, (5) attention deficit disorder, (6) autistic disorder, (7) bipolar disorder, (8) seizures, (9) cerebral palsy, (10) dementia, (11) depressive disorder, (12) Down syndrome, (13) dystonia, (14) encephalomyelitis, (15) epilepsy, (16) schizophrenia, (17) hydrocephalus, (18) mental retardation, (19) microcephaly, (20) multiple sclerosis, (21) neuroacanthocytosis, (22) neuroaxonal dystrophies, (23) obsessive-compulsive disorder.