Table 3.
Interactions of LRRK2 p.R1398H with SNCA variants in regard to susceptibility to PD in the Asian series
| Test of association | |||||
|---|---|---|---|---|---|
|
| |||||
| Variant/Genotype | LRRK2 p.R1398H | Sample genotype count and frequency | OR (95% CI) | P-value | Test of interaction |
| Additive/Genotype models1 | |||||
| SNCA rs356219 | |||||
| AA | GG | 282 (12.9%) | 1.00 (reference) | N/A | Additive model |
| AA | GA or AA | 83 (3.8%) | 0.64 (0.39 – 1.06) | 0.087 | OR: 1.17 |
| AG | GG | 808 (37.0%) | 1.59 (1.21 – 2.09) | 0.0009 | 95% CI: 0.87 – 1.59 |
| AG | GA or AA | 232 (10.6%) | 1.19 (0.84 – 1.69) | 0.33 | P=0.30 |
| GG | GG | 623 (28.5%) | 2.09 (1.56 – 2.79) | 6E-7 | Genotype model 4 |
| GG | GA or AA | 156 (7.1%) | 1.84 (1.23 – 2.77) | 0.0031 | P=0.59 |
| SNCA rs11931074 | |||||
| GG | GG | 302 (13.3%) | 1.00 (reference) | N/A | Additive model |
| GG | GA or AA | 89 (3.9%) | 0.61 (0.37 – 0.98) | 0.044 | OR: 1.25 |
| GT | GG | 843 (37.2%) | 1.55 (1.19 – 2.02) | 0.0012 | 95% CI: 0.93 – 1.69 |
| GT | GA or AA | 243 (10.7%) | 1.06 (0.75 – 1.49) | 0.75 | P=0.14 |
| TT | GG | 630 (27.8%) | 1.90 (1.43 – 2.51) | 7.8E-6 | Genotype model 4 |
| TT | GA or AA | 158 (7.0%) | 1.75 (1.18 – 2.61) | 0.0059 | P=0.31 |
| Dominant model2 | |||||
| SNCA rs356219 | |||||
| AA | GG | 282 (12.9%) | 1.00 (reference) | N/A | OR: 1.23 95% CI: 0.71 – 2.14 P=0.47 |
| AA | GA or AA | 83 (3.8%) | 0.64 (0.39 – 1.06) | 0.087 | |
| AG or GG | GG | 1431 (65.5%) | 1.78 (1.38 – 2.31) | 1.10E-5 | |
| AG or GG | GA or AA | 388 (17.8%) | 1.41 (1.03 – 1.92) | 0.030 | |
| SNCA rs11931074 | |||||
| GG | GG | 302 (13.3%) | 1.00 (reference) | N/A | OR: 1.25 95% CI: 0.74 – 2.15 P=0.41 |
| GG | GA or AA | 89 (3.9%) | 0.61 (0.37 – 0.98) | 0.043 | |
| GT or TT | GG | 1473 (65.0%) | 1.69 (1.31 – 2.17) | 4.3E-5 | |
| GT or TT | GA or AA | 401 (17.7%) | 1.28 (0.95 – 1.73) | 0.11 | |
| Recessive model3 | |||||
| SNCA rs356219 | |||||
| AA or AG | GG | 1090 (49.9%) | 1.00 (reference) | N/A | OR: 1.22 95% CI: 0.78 – 1.92 P=0.38 |
| AA or AG | GA or AA | 315 (14.4%) | 0.72 (0.56 – 0.93) | 0.011 | |
| GG | GG | 623 (28.5%) | 1.48 (1.21 – 1.83) | 0.0002 | |
| GG | GA or AA | 156 (7.1%) | 1.31 (0.93 – 1.87) | 0.13 | |
| SNCA rs11931074 | |||||
| GG or GT | GG | 1145 (50.6%) | 1.00 (reference) | N/A | OR: 1.39 95% CI: 0.90 – 2.17 P=0.14 |
| GG or GT | GA or AA | 332 (14.7%) | 0.66 (0.52 – 0.85) | 0.0011 | |
| TT | GG | 630 (27.8%) | 1.38 (1.12 – 1.69) | 0.0020 | |
| TT | GA or AA | 158 (7.0%) | 1.27 (0.90 – 1.80) | 0.18 | |
ORs and p-values result from fixed-effects logistic regression models. For tests of association, the two given variants were combined into one variable, and the model was adjusted for site. For tests of interaction, models included each of the two variants, their interaction, and site. Additive models, genotype models, dominant models, and recessive models refer to the characterization of SNCA variants; only dominant models were considered for LRRK2 p.R1398H due to the small number of rare homozygotes for this variant.
Interaction ORs under an additive model are interpreted as the multiplicative increase in the effect of the minor allele for LRRK2 p.R1398H on PD corresponding to each additional risk allele for SNCA variants, or alternatively as the as the multiplicative increase in the effect of each additional risk allele for SNCA variants on PD corresponding to presence of the minor allele for LRRK2 p.R1398H.
Interaction ORs under a dominant model are interpreted as the multiplicative increase in the effect of the minor allele for LRRK2 p.R1398H on PD corresponding to presence of the risk allele for SNCA variants, or alternatively as the as the multiplicative increase in the effect of presence of the risk allele for SNCA variants on PD corresponding to presence of the minor allele for LRRK2 p.R1398H..
Interaction ORs under a recessive model are interpreted as the multiplicative increase in the effect of the minor allele for LRRK2 p.R1398H on PD corresponding to presence of two risk alleles for SNCA variants, or alternatively as the as the multiplicative increase in the effect of presence of two risk alleles for SNCA variants on PD corresponding to presence of the minor allele for LRRK2 p.R1398H.
Tests of interaction under a genotype model do not produce a single interaction OR, and therefore only a p-value is given. OR=odds ratio. CI=confidence interval.