Table 3. Meta-analysis of the associations of compound genotypes with Alzheimer’s disease (AD) Aβ42 and tau biomarkers.
| Biomarker | Source | Genotype | N | Beta | SE | P value | Direction |
| Aβ42 | CSF | 0XY | 59 | 0.026 | 0.055 | 6.37E-01 | −+???? |
| Aβ42 | CSF | 100+200 | 56 | −0.272 | 0.057 | 2.13E-06 | −−???? |
| Aβ42 | CSF | 111+222 | 178 | −0.341 | 0.039 | 2.46E-18 | −−???? |
| Aβ42 | CSF | 1XY+2XY | 242 | −0.373 | 0.037 | 2.18E-24 | −−???? |
| Aβ42 | CSF | 000 | 237 | Reference | |||
| Aβ42 | Plasma | 0XY | 951 | 0.351 | 0.364 | 3.35E-01 | −?−−++ |
| Aβ42 | Plasma | 100+200 | 396 | −2.305 | 0.551 | 2.82E-05 | −?−−−− |
| Aβ42 | Plasma | 111+222 | 1462 | −1.582 | 0.312 | 4.14E-07 | −?−−−− |
| Aβ42 | Plasma | 1XY+2XY | 1821 | −1.656 | 0.287 | 7.98E-09 | −?−−−− |
| Aβ42 | Plasma | 000 | 5549 | Reference | |||
| Tau | CSF | 0XY | 70 | 0.088 | 0.050 | 7.97E-02 | ++???? |
| Tau | CSF | 100+200 | 56 | 0.233 | 0.056 | 2.85E-05 | ++???? |
| Tau | CSF | 111+222 | 189 | 0.293 | 0.035 | 4.87E-17 | ++???? |
| Tau | CSF | 1XY+2XY | 253 | 0.294 | 0.032 | 6.75E-20 | ++???? |
| Tau | CSF | 000 | 326 | Reference | |||
| Tau | Plasma | 0XY | 647 | 0.009 | 0.013 | 4.91E-01 | −?−+−? |
| Tau | Plasma | 100+200 | 289 | −0.045 | 0.018 | 1.28E-02 | +?−−−? |
| Tau | Plasma | 111+222 | 1033 | −0.010 | 0.011 | 3.66E-01 | +?−−−? |
| Tau | Plasma | 1XY+2XY | 1280 | −0.002 | 0.010 | 8.42E-01 | +?−−−? |
| Tau | Plasma | 000 | 3913 | Reference | |||
Column “Genotype” shows compound genotypes encoded by triples of numbers and X and Y letters. Numbers show the counts of minor alleles (i.e., 0, 1, 2) in rs429358_T/c, rs2075650_A/g or rs12721046_G/a SNP, in that order. The upper/lower case denotes here major/minor allele. The most frequent 000 genotype denotes the major allele homozygote for all three SNPs, i.e., rs429358_TT, rs2075650_AA, rs12721046_GG. The 100+200 genotype indicates rs429358_Tc, rs2075650_AA, rs12721046_GG (100) and rs429358_cc, rs2075650_AA, rs12721046_GG (200). The 111+222 genotype denotes rs429358_Tc, rs2075650_Ag, rs12721046_Ga (111) and rs429358_cc, rs2075650_gg, rs12721046_aa (222). Letters X and Y indicate aggregation of minor alleles of rs2075650 and rs12721046, respectively. Then, 0XY aggregates all non-ε4 genotypes except 000. The 1XY+2XY genotype aggregates rs429358_Tc (1) and rs429358_cc (2) and all genotypes of rs2075650 (X) and rs12721046 (Y), except major allele homozygote of both SNPs, rs2075650_AA and rs12721046_GG (00), because it is included in the 100+200 genotype. Column “Direction” shows sign of the effect beta in individual studies in the following order: ADNI-1, ADNI-2/GO, FHS_C1, FHS_C2, FHS_C3, and ARIC. Question mark indicates missing estimates. Note, cerebrospinal fluid (CSF) biomarkers were available only in ADNI cohorts; plasma biomarkers were not available in ADNI-2/GO, and tau was not reported in ARIC. A gamma general linear model with a log link function was used for all biomarkers except Aβ42 measured in plasma. SE denotes standard error. More details with individual-study estimates are given Supplementary Table 5.