Table 2.
Summary of association studies of established or candidate SLD/dyslexia genes.
| Phenotype (Trait/Subphenotype) |
Gene(s) | Variant(s) Associated with Phenotype or Trait | Sample Size and Study Design | Reference |
|---|---|---|---|---|
| Genes Residing in Classical DYX Loci | ||||
| Dyslexia/PA, RAN, and other traits | DYX1C1 | rs11629841 and haplotypes of rs11629841 with rs3743204 and rs692691 | 148 nuclear families (470 individuals) |
[76] |
| Dyslexia | DYX1C1 | No association | 264 nuclear families (1153 individuals) |
[77] |
| Dyslexia | DYX1C1 | c.1249G>T coding variant | 191 trios | [78] |
| Dyslexia/short-term memory | DYX1C1 | c.−3G>A and c.1249G>T minor alleles haplotype | 212 nuclear families (677 individuals) |
[79] |
| Dyslexia/short-term memory | DYX1C1 | rs3743205/rs3743204/ rs600753 haplotype in females |
366 trios | [80] |
| Reading ability (reading and spelling traits) |
DYX1C1 | rs17819126 coding variant | 284 DZ twins, 164 DZ twin families, 143 MZ twin families | [81] |
| Dyslexia/Reading ability (12 cognitive traits) |
DCDC2 | 10/31 SNPs in DCDC2 | 153 nuclear families (536 individuals) |
[82] |
| Dyslexia | DCDC2 | No association |
396 trios | [83] |
| Dyslexia (severe versus non-severe) |
DCDC2 | rs793862, rs807701, rs80772 and intron-2 deletion | 72 cases/184 controls | [84] |
| Reading ability (7 reading and spelling traits) |
DCDC2 | 21 SNPs of which rs1419228 was associated with poorer general reading performance | 522 twin families (1067 individuals) (unselected population) |
[85] |
| Dyslexia/word-reading and spelling | DCDC2 | rs793862 and rs807724 minor alleles in SLD or comorbid cases | 225 cases/442 controls (plus 54 comorbid SLD/SLI/ADHD cases) |
[86] |
| Dyslexia and mathematics (numerical facts and mental calculation) | DCDC2 and DYX1C1 | c.−3G>A, c.1249G>T in DYX1C1 and intron-2 deletion/STR in DCDC2 | 180 nuclear families (581 individuals) |
[87] |
| Dyslexia/6 traits of reading ability | DCDC2 | Intron-2 STR alleles associated with word- and non-word repetition | 303 nuclear families (973 individuals) |
[88] |
| Dyslexia | DCDC2 | 14 SNPs of which several SNPs and two haplotypes were associated under different models | 196 cases/196 controls | [89] |
| Dyslexia/6 traits of reading ability | DCDC2 and KIAA0319 | 5 SNPs within KIAA0319 Pairwise associations between a DCDC2 and a KIAA0319 variant |
264 nuclear families 350 cases/273 controls |
[90] |
| Reading abilities (5 reading and spelling traits) |
KIAA0319 | rs2143340 associated with poor reading and spelling | ~6000 individuals | [91] |
| Dyslexia/6 traits of reading ability | KIAA0319 | rs9461045 associated with dyslexia traits | 264 nuclear families (of which 126 comprised a severity sample) |
[92] |
| Dyslexia/Reading, spelling, and phonological traits |
DCDC2 and KIAA0319 NRSN1 |
rs6935076 in KIAA0319 associated with dyslexia and spelling and 3 SNPs in NRSN1 | 291 nuclear families (of which 165 are trios) |
[93] |
| General reading abilities (word-reading and spelling) | KIAA0319 and CMIP | rs2143340 in KIAA0319 and rs6564903 in CMIP | 225 cases/442 controls (plus 54 comorbid SLD/SLI/ADHD cases) |
[86] |
| Dyslexia and mathematics | ROBO1 | rs333491 associated with mental calculation accuracy | 179 nuclear families (of which 154 comprised a severity sample) |
[94] |
| Dyslexia Word-reading efficiency and RAN |
KIAA0319L
KIAA0319L |
rs7523017 associated with dyslexia A four SNP-haplotype |
291 nuclear families 156 nuclear families |
[95] |
| Other dyslexia-candidate genes | ||||
| Dyslexia/6 traits of reading ability | CNTNAP2 | rs2710102 associated with non-word repetition | 188 trios | [96] |
| Dyslexia/6 traits of reading ability | FOXP2 | rs7782412 major allele associated with non-word repetition and real-word reading efficiency | 188 trios | [96] |
| Dyslexia (mismatch response) |
SLC2A3 | rs4234898 on chromosome 4 associated with mismatch response | 200 cases (discovery set) 186 cases (replication set) | [97] |
| Dyslexia/IQ and cognitive processes and mathematics | GRIN2B | rs5796555 and rs1012586 associated with dyslexia | 466 nuclear families, of which 227 comprised a severity sample | [98] |
| Reading ability (reading comprehension, phonological memory) |
BDNF | rs6265 associated with poorer reading performance rs6265 associated with increased brain activity in areas contributing to phonological and reading competence |
81 children 94 children |
[99] [100] |
| Dyslexia-associated gene panels | ||||
| Dyslexia/word-reading and spelling | DYX1C1, DCDC2, KIAA0319, and MRPL19/C2orf3 locus | No association | 958 cases/1150 controls | [72] |
| Dyslexia | MRPL19, C20RF3, ROBO1, DCDC2, KIAA0319, DYX1C1, CNTNAP2, ATP2C2 and CMIP | rs807724 in DCDC2 associated with dyslexia | 331 cases/maximum 363 controls | [101] |
| Dyslexia/spelling | CYP19A1, DCDC2, DIP2A, DYX1C1, GCFC2 (C2orf3), KIAA0319, MRPL19, PCNT, PRMT2, ROBO1 and S100B | A non-synonymous SNP in DCDC2 (rs2274305) and a non-coding SNP in S100B (rs9722) associated with dyslexia | 361 cases/261 controls 575 affected, 376 unaffected and 511 of unknown status (family-based) |
[102] |
| Dyslexia | DYX1C1, DCDC2, KIAA0319, ROBO1 and TDP2 | Nominal associations only (rs7765678 in DCDC2, rs2038137 and rs6935076 in KIAA0319) |
383 cases/357 controls | [38] |
| Reading abilities (Word/Non-word reading fluency, PA, RAN) |
Top hits from previous GWAS on reading (SLD) and language (SLI) (dis)abilities | No association | 307 nuclear families (483 children/505 adults) |
[103] |
| Reading ability | CYP19A1, DCDC2, DYX1C1, GCFC2 (C2orf3), KIAA0319, MRPL19, ROBO1, KIAA0319L DIP2A, PRMT2, PCNT, S100B, CNTNAP2 and CMIP | No single-marker association 62 SNPs—Gene-based SNP-set associations were significant for DYX1C1, DIP2A, CYP19A1 |
1217 old adults (>70 yrs) (unimpaired) |
[104] |
| Dyslexia Word reading, RAN, and syllable discrimination |
KIAA0319, DCDC2, and DYX1C1 | No single-marker association Pairwise SNP association with dyslexia (rs2274305 in DCDC2 and rs4504469 in KIAA0319) rs2274305 in DCDC2 rs57809907 in DYX1C1 rs4504469 in KIAA0319 |
286 cases/1197 controls 3357 individuals (total cohort) |
[73] |
| Reading and spelling ability |
CMIP, CNTNAP2, CYP19A1, DCDC2, DIP2A, DYX1C1, C2orf3, KIAA0319, KIAA0319L, MRPL19, ROBO1, PCNT, PRMT2 and S100B |
No association (>9500 SNPs and gene-based SNP-sets) |
1505 individuals (unimpaired) |
[75] |
| Other SLD domains | ||||
| Reading and mathematical traits indicative of dyslexia and dyscalculia, respectively | 15q11.2(BP1-BP2)—TUBGCP5, NIPA1, NIPA2, CYFIP1 | 15q11.2(BP1-BP2) deletion CNV associated with worse outcome in reading and mathematical abilities | 167 controls, carriers of neuropsychiatric CNVs | [43] |
| Dysgraphia | DCDC2, DYX1C1, KIAA0319 and ROBO1 | rs3743204 in DYX1C1 and rs793842 in DCDC2 associated with dysgraphia measurements | 21 cases/18 controls | [105] |
PA: phonological awareness, RAN: rapid automatized naming, SNP: single nucleotide polymorphism, cases = dyslexic cases, controls = unimpaired individuals, DZ: dizygotic (twins), MZ: monozygotic (twins), STR: short tandem repeat.