Table 1.
AD-associated ABCA7 (epi-) genetic variation
| Variation | Interpretation | Origin | OR | MAFgnomAD (%) |
|---|---|---|---|---|
| Common risk-increasing variants | ||||
| rs3764650 | Intronic GWAS sentinel SNP, low predicted functional effect | CA | 1.2 [1.1–1.3] | 8.4 |
| rs4147929 | Intronic GWAS sentinel SNP, low predicted functional effect | CA | 1.1 [1.1–1.2] | 17.1 |
| rs3752246 | Missense GWAS sentinel SNP p.Gly1527Ala, predicted benign | CA | 1.2 [1.1–1.2] | 17.0 |
| rs78117248 | NGS-identified intronic candidate SNP, low predicted functional effect | CA | 2.1 [1.3–3.3] | 2.4 |
| ABCA7 VNTR expansions | Reduced ABCA7 expression, loss of exon 19 encoding an ATP-binding domain | CA | 4.5 [1.3–24.2] | 0.8 |
| rs115550680 | Intronic GWAS sentinel SNP, low predicted functional effect | AA | 1.8 [1.5–2.1] | 6.2 |
| rs142076058 | PTC variant p.Arg578 fs, loss-of-function | AA | 1.8 [1.4–2.4] | 5.7 |
| Rare variants | ||||
| PTC variants | Loss-of-function | CA | 2.6 [1.3–5.5]* | 1.1** |
| PTC variants | Loss-of-function | AA | 1.4 [1.0–1.9] | 7.3** |
| Missense variants | Unclear, misfolding and/or increased protein degradation? | CA | 1.8 [1.3–2.4]* | / |
| Common protective variant | ||||
| rs72973581 | Missense variant p.Gly215Ser, change into evolutionary conserved amino acid | CA | 0.6 [0.4–0.95] | 6.3 |
| CpG methylation | ||||
| cg02308560 | Hypermethylation in AD, Polycomb repression, effect on ABCA7 unknown | CA | Est. = 7.7 (s.e. = 1.7) | / |
| cg24402332 | Hypermethylation in AD, effect on ABCA7 unknown | CA | Est. = 12.4 (s.e. = 3.4) | / |
| cg04587220 | Hypermethylation in AD, Polycomb repression, effect on ABCA7 unknown | CA | Est. = 4.7 (s.e. = 1.4) | / |
| CpG island shore (chr19:1045074–1045679) | Hypomethylation in AD, effect on ABCA7 unknown | CA | log2FC = − 0.28 | / |
Variants and CpG methylation sites in ABCA7 with reported association to AD are shown along with their interpreted functional effect, the origin of the study cohort, odds ratios (OR) with 95% confidence intervals, and origin-matched minor allele frequencies (MAF) in community-dwelling individuals from gnomAD
CA Caucasian, AA African American, Est. regression estimate, s.e. standard error, log2FC log2 fold change,
*Meta-analysis OR from this review
**Cumulative frequencies