Table 2.
CpG sites significantly associated with cerebral white matter, total grey matter, and whole-brain volume (N = 672), along with gene annotations (Gene), chromosome (c), standardized effect size (β), nominal (P-value) and multiple comparison-corrected p-values (P-corr). Traits previously associated with each CpG site were extracted from EWAS catalogues (http://www.ewascatalog.org/, association between traits and CpGs on Illumina 450 K array at p ≤ 1.0x10−4; and http://www.bioapp.org/ewasdb/ [60],), association between traits and CpGs on Illumina 450 K and EPIC arrays at p ≤ 1.0x10−3). Gene information was extracted from the GWAS catalogue (https://www.ebi.ac.uk/gwas/; associations between traits and SNPs at p < 1.0x10− 5). All associations included in the table from these two catalogues are genome-wide significant.
| Phenotype | CpG site | Gene | C | β | P-value | P-corr | CpG – previously associated traits |
Gene – previously associated traits |
|---|---|---|---|---|---|---|---|---|
| Total grey matter | cg07585845 (EPIC) | - | 3 | 9.59x10−7 | 1.02x10−9 | 0.0007 | - | - |
| Whole- brain volume | cg07585845 (EPIC) | - | 3 | 4.47x10−7 | 1.38x10−8 | 0.009 | ||
| Total grey matter | cg02325951 (450 K) | FOXN3 | 14 | 6.53x10−7 | 1.31x10−9 | 0.0009 | Sex (p = 2x10−54; 1.8x10−42; [54]) | Acute myeloid leukaemia (p = 8x10−21 p = 3x10−14; [61]) Heel bone mineral density (p = 2x10−12; [62]) Intelligence (p = 1x10−11; [79]) Self-reported educational attainment (p = 8x10−11; [80]) Cognitive function measurement (p = 2x10−9; [80]) Mathematical ability (p = 3x10− 9; [80]) Smoking status measurement (p = 7x10−9; [63]) Risk-taking behaviour (p = 8x10− 9; [64]) |
| Whole- brain volume | cg02325951 (450 K) | FOXN3 | 14 | 3.26x10−7 | 1.45x10−9 | 0.001 | ||
| Cerebral white matter | cg10297662 (EPIC) | PNKP | 19 | −1.46x10−6 | 4.92x10−8 | 0.03 | - | Involved in DNA repair; mutations at locus associated with microcephaly, seizures, and developmental delay [73] |
| Total grey matter | cg04190002 (450 K) | SHANK3 | 22 | −3.75x10−7 | 7.31x10−9 | 0.04 | Sex (p = 5.4x10− 19; [79]) | Self-reported educational attainment (p = 2x10−20; [80]) Mathematical ability (p = 1x10− 17; [80]) Cognitive function measurement (p = 3x10−12; [80]) Schizophrenia (p = 3x10−12; [82]) |