The frequencies of ALS variants are population specific
| Gene | Variant | % Italian (n=1003) | % Irish (n=444) | p Value |
|---|---|---|---|---|
| ANG | c.232A>G(p.K54E) | 0.1 | 0 | 0.56* |
| c.338G>A(p.W89X) | 0.1 | 0 | ||
| c.433C>T(p.R121C) | 0.1 | 0 | ||
| C9orf72 | Repeat Expansion | 4.39 | 8.78 | 3.95×10−4* |
| FUS | c.1542G>C(p.R514S) | 0.1 | 0 | 0.18†, 0.61* |
| c.1562G>T(p.R521L) | 0.1 | 0 | ||
| c.1574C>T(p.P525L) | 0.1 | 0.45 | ||
| OPTN | c.1192C>G(p.GLn398Glu) | 0 | 0.23 | 1†, 1* |
| c.1499T>C(p.L500P) | 0.1 | 0 | ||
| c.1703T>C(p.L568S) | 0.1 | 0 | ||
| SOD1 | c.34G>T(p.D11Y) | 0.3 | 0 | 3.7×10−3* |
| c.59A>G(p.N19S) | 0.1 | 0 | ||
| c.63C>G(p.F20L) | 0.1 | 0 | ||
| c.115C>G(p.L38V) | 0.1 | 0 | ||
| c.142G>T(p.V47F) | 0.1 | 0 | ||
| c.203T>C(p.L67P) | 0.1 | 0 | ||
| c.256G>A(p.G85S) | 0.1 | 0 | ||
| c.271G>A(p.D90N) | 0.1 | 0 | ||
| c.272A>C(p.D90A) | 0.3 | 0 | ||
| c.281G>A(p.G93D) | 0.3 | 0 | ||
| c.328G>T(p.D109Y) | 0.2 | 0 | ||
| c.400_402delGAA(p.E133del) | 0.1 | 0 | ||
| c.435G>C(p.L144F) | 0.1 | 0 | ||
| TARDBP | c.800A>G(p.N267S) | 0.2 | 0 | 0.026†, 0.035* |
| c.859G>A(p.Gly287Ser) | 0 | 0.45 | ||
| c.881G>T(p.G294V) | 0.2 | 0 | ||
| c.909A>C(p.Q303H) | 0.1 | 0 | ||
| c.1009A>G(p.M337V) | 0.1 | 0 | ||
| c.1102G>A(p.G368S) | 0.1 | 0 | ||
| c.1144G>A(p.A382T) | 0.9 | 0 | ||
| c.1147A>G(p.I383V) | 0.1 | 0 | ||
| c.1169A>G(p.N390S) | 0.3 | 0 | ||
| Combined | – | 9.07 | 9.91 | 1.7×10−4†, 0.25* |
Analysed variants include the C9orf72 hexanucleotide repeat expansion and non-synonymous variants reported as patient specific. Analysis of TARDBP was restricted to exon 6 while analysis of FUS was restricted to exons 14 and 15 and analysis of OPTN was restricted to exons 5, 9, 12 and 14.3.
*Comparison of combined variant frequencies using a Fisher exact test.
†Comparison of independent variant frequencies using a c-α test.
ALS, amyotrophic lateral sclerosis.