Genetic modifiers in carriers of repeat expansions in the C9ORF72 gene

Table 2 Variants significantly associated with age at onset or survival after onset

Variant (gene/disease group)	Number of patients with each genotype^a	Model	Association measure (95% CI)	P-value
Age at onset (overall)			Regression coefficient
rs7018487 (UBAP1)	122 / 96 / 23	Additive	−2.62 (−4.36, −0.89)	0.003
rs6052771 (PRNP)	92 / 104 / 46	Recessive	4.42 (1.51, 7.32)	0.003
rs7403881 (MT-Ie)	65 / 118 / 60	Dominant	3.95 (1.36, 6.54)	0.003
Survival after onset (overall)			Relative risk
rs5848 (GRN)	116 / 86 / 19	Additive	1.64 (1.22, 2.22)	0.001
Survival after onset (disease subgroups)			Relative risk
rs7403881 (MT-Ie): FTD	13 / 31 / 14	Recessive^b	3.81 (1.71, 8.46)	0.001
rs13268953 (ELP3): FTD	16 / 31 / 11	Recessive	3.65 (1.56, 8.55)	0.003
Epsilon 4 (APOE): FTD	42 / 13 / 2	Dominant	3.13 (1.45, 6.74)	0.004
rs12608932 (UNC13A): MND	44 / 40 / 23	Recessive^b	5.65 (1.82, 17.58)	0.003
rs1800435 (ALAD): MND	88 / 18 / 1	Dominant	N/A^c	0.003

Association measure = regression coefficient (age at onset analysis) and relative risk (survival after onset analysis); CI = confidence interval. Additive models, dominant models, and recessive models were utilized. We adjusted for multiple testing using a false discovery rate (FDR) of 10%. ^aOrder of genotypes: major-major/major-minor/minor-minor. ^bIndicates that the variant was also significantly associated with the given outcome under an additive model. ^cFor rs1800435, none of the 19 MND patients (0.0%) who carried the minor allele died as compared to 14 of 78 MND patients (15.9%) who did not carry the minor allele; the p-value of 0.003 results from a log-rank test. The strongest association with the given outcome is displayed in this table; other associations are shown in Additional file 1: Table S2 (age at onset) and Additional file 1: Table S3 (survival after onset).

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