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. 2023 Oct 4;15:79. doi: 10.1186/s13073-023-01233-z

Table 3.

Mediation models. Results from structural equation models testing the hypothesis, that SNP effects on CSF biomarker PCs would also affect AD risk

SNP Chr:Pos Location Locus EA EAF R2imp Sex PC1 PC2 PC3 PC4 PC5 PC Prop Direct Total ZAD (Wightman et al.) [42]
Tau pathology/Degeneration (PC1)
 rs140169162 17:30886881 Intron MYO1D G 0.98 0.69 m 0.02 0.10 −0.03 0.01 0.00 0.11 0.29 0.26 0.36 −1.94
f 0.52* −0.12 −0.04 −0.01 0.00 0.35* −1.04* −0.69
Aβ Pathology (PC2)
 rs1638675 10:119178376 Intergenic - A 0.57 0.89 m 0.03 0.10* −0.03 0.00 0.00 0.10* −0.06 0.04 −0.18
f 0.02 −0.04* 0.00 0.00 0.00 −0.02 0.07 0.04
Tau pathology/Degeneration & Aβ Pathology (PC1 & PC2)
 rs12972156 19:45387459 Intron APOE C 0.74 0.98 all −0.07* −0.12* 0.02 0.00 0.00 −0.17* 0.65 −0.09 −0.27* −Inf*
 rs157582 19:45396219 Intron APOE C 0.65 1.00 all −0.08* −0.11* 0.01 0.00 0.00 −0.17* 0.79 −0.05 −0.22* −Inf*
 rs10119 19:45406673 3′-UTR APOE G 0.60 0.95 all −0.06* −0.10* 0.01 0.00 0.00 −0.15* 0.67 −0.07 −0.23* −Inf*
 rs429358 19:45411941 Exon APOE T 0.70 0.99 all −0.09* −0.13* 0.01 0.00 0.00 −0.21* 0.54 −0.18* −0.39* −Inf*
 rs75627662 19:45413576 Intergenic APOE C 0.71 0.98 all −0.06* −0.10* 0.02 0.00 0.00 −0.14* 0.59 −0.10 −0.24* −Inf*
 rs157595 19:45425460 Intergenic APOE A 0.33 0.96 all −0.06* −0.09* 0.02 0.00 0.00 −0.13* 0.54 −0.11 −0.23* −29.68*
 rs111789331 19:45427125 Intergenic APOE T 0.73 0.95 all −0.08* −0.12* 0.02 0.00 0.01 −0.19* 0.57 −0.14 −0.33* −Inf*
Injury/Inflammation (PC3)
 rs7551263 1:203150756 Intron CHI3L1 T 0.84 0.99 all 0.04 −0.01 0.05* −0.02 0.00 0.06 −0.11 −0.05 1.21
 rs114211800 5:158973225 Intron LOC105377684 G 0.98 0.91 m 0.11 −0.08 −0.31* 0.00 0.00 −0.29* 0.27 −0.02 0.45
f −0.09 −0.05 0.03 0.01 0.00 −0.09 0.58 0.49
 rs2302634 7:12270770 Intron TMEM106B T 0.58 1.00 all −0.02 −0.01 0.07* 0.00 0.00 0.04 −0.08 −0.04 5.38*
 rs56194026 15:74831534 Intergenic ARID3B C 0.92 0.90 m −0.03 0.01 −0.13* 0.01 0.00 −0.15* 0.09 −0.06 −0.03
f −0.01 −0.03 0.10* 0.00 0.00 0.06 −0.18 −0.12 −0.01
No evidence for mediation
 rs10399931 1:203156080 Intergenic CHI3L1 T 0.24 0.98 all 0.04 −0.03 0.02 −0.03 0.00 −0.01 0.10 0.10 0.58
 rs12670437 7:76390507 Intergenic - G 0.98 0.87 all −0.10 0.05 −0.01 −0.01 0.00 −0.07 0.54 −0.06 −0.14 0.22
 rs145791381 9:24796757 Intergenic - T 0.98 0.93 all 0.00 −0.01 0.10 −0.03 0.00 0.06 −0.08 −0.02 2.20*
 rs16974493 13:110307768 Intergenic - T 0.97 0.98 all −0.01 0.01 0.01 0.02 0.00 0.03 −0.07 −0.03 0.34
 rs150326618 14:52641990 Intergenic - G 0.98 0.80 all −0.08 −0.02 −0.07 0.03 0.00 −0.15 0.19 −0.62 −0.77 −0.22
 rs275844 19:48884949 Intergenic GRIN2D G 0.88 0.93 m −0.07 0.02 −0.01 0.00 0.00 −0.06 0.18 0.12 −2.13*
f −0.02 0.05 0.02 −0.01 0.00 0.05 −0.18 −0.13
 rs8111684 19:48947326 3′-UTR GRIN2D G 0.26 1.00 all 0.02 0.00 −0.02 0.00 0.00 0.00 0.04 −0.01 −0.01 0.72
 rs3107911 19:48964305 Intron GRIN2D C 0.15 0.96 all 0.02 0.00 −0.01 0.00 0.00 0.00 0.03 −0.05 −0.05 1.31

SNP RS ID, Chr:Pos Chromosome:Position Build 37, EA effect allele, SE standard error, R2imp Imputation Quality, Sex In case of significant differences in mediation pathways between males and females based on moderated mediation models, pathway estimates are given separately for males and females, PC1-PC5 The effect of one copy of the effect allele on latent AD in SD via mediation of the biomarker PC, PC1 Tau pathology/Degeneration, PC2 Aβ Pathology, PC3 Injury/Inflammation, PC4 Non-AD Inflammation, PC5 Non-AD Synaptic Functioning, PC Joint effect of all mediation pathways via any biomarker, Prop. Proportion of mediated effect (PC/Total), Direct The effect of one copy of the effect allele on latent AD in SD not mediated by any biomarker PC, Total The joint effect of one copy of the effect allele on latent AD in SD by either mediation or direct effects, ZAD (Wightman et al.) [42] Z test statistic based on previous GWAS of AD

*p < 0.008