Table 2 Replication of genetic association tests for age of onset of Huntington's disease in Venezuelan kindreds.
| Candidate gene | Polymorphism | Number of affected analysed (n) | R2 CAG length only | R2 CAG + Cand. gene | p Value for multiple regression | Protective genotype(s) | Detrimental genotype(s) | Difference in average age of onset (years) | p Value for t‐test | Phase matches? | p Value for QTDT |
|---|---|---|---|---|---|---|---|---|---|---|---|
| HD | Δ2642 | 375 | 0.707 | 0.707 | NS | WT {96%} | Δ2642 {4%} | 0.04 | NS | Yes | NS |
| (CCG)n | 306 | 0.747 | 0.750 | NS | (CCG)7 {92%} | (CCG)10 {5%} | 2.0 | NS | Yes | NS | |
| Shorter (CAG)n | 443 | 0.729 | 0.730 | NS | Lower repeat lengths | Higher repeat lengths | NS | No and Yes* | NS | ||
| GRIK2 | (TAA)n | 368 | 0.741 | 0.745 | NS | All others | (TAA)16 | 4.6 | NS | Yes | 0.09 for (TAA)13 |
| APOE | ε2/ε3/ε4 | 423 | 0.679 | 0.680 | NS | ε3 {77%} | ε4 {10%} | 2.0 | NS | No | NS |
| TCERG1 | (Gln‐Ala)n | 427 | 0.727 | 0.733 | 0.08 | 306 bp | All others | 5.1 | NS | Yes | 0.07 for 306 bp |
| UCHL1 | Ser18Tyr | 405 | 0.731 | 0.734 | NS | Ser {87%} | Thr {13%} | 0.3 | NS | Yes | NS |
| TP53 | Arg72Pro | 429 | 0.729 | 0.729 | NS | Arg {62%} | Pro {38%} | 0.7 | NS | No | NS |
| DFFB | Arg196Lys | 429 | 0.728 | 0.730 | 0.10 | Lys {10%} | Arg {90%} | 3.0 | NS | No | 0.02 |
| GRIN2B | C/T SNP | 337 | 0.747 | 0.747 | NS | C {74%} | T {26%} | 1.7 | NS | Yes | NS |
| T/G SNP | 305 | 0.756 | 0.757 | NS | G {49%} | T {51%} | 1.1 | NS | No | NS | |
| GRIN2A | C/T SNP | 421 | 0.729 | 0.732 | 0.04 | T {76%} | C {24%} | 2.6 | NS | Yes | 0.07 |
| T/T | T/C | 3.9 | 0.05 | Yes |
*Divergent effects have been reported in different publications (table 1).
All statistical tests controlled for the effect of CAG repeat length on age of onset: the comparisons of R2 values starts with the correlation of CAG repeat length alone; the comparisons of mean ages of onset for allelic or genotypic classes used CAG repeat length as a covariate, and the QTDT test used residual ages of onset that removed the effect of CAG repeat length. Overall allele frequency in the Venezuelan sample is noted in braces in the “Protective genotype” and “Detrimental genotype” columns, or in tables 3 (for GRIK2) and 4 (for TCERG1 and GRIN2A). Non‐significant results (NS) indicate p Values >0.1.