Exome sequencing study in patients with multiple sclerosis reveals variants associated with disease course

Table 2 Summary of statistical analysis of selected SNPs in the discovery and validation cohorts

Selected variants			Discovery cohort (n = 20)			First validation cohort (n = 194)		Second validation cohort (n = 257)		Meta-analysis
SNP	Gene	Minor allele	MAF, Benign (n = 10)	MAF, Aggressive (n = 10)	p value	MAF, Benign (n = 107)	MAF, Aggressive (n = 87)	MAF, Benign (n = 224)	MAF, Aggressive (n = 33)	Joint p value	OR (95% CI)
rs17844444	PCDHB6	A	0.10	0.40	0.03	0.15	0.15	0.18	0.14	0.52
rs17082236	SYNE1	A	0.00	0.35	0.003	0.09	0.1	0.05	0.07	0.54
rs10279499	SAMD9	A	0.45	0.00	0.0006	0.12	0.12	0.10	0.04	0.29
rs10488532	SAMD9L	T	0.45	0.00	0.0006	0.12	0.14	0.12	0.06	0.79
rs2374639	VPS50	C	0.60	0.06	0.003	0.27	0.31	0.27	0.15	(*)
rs17552167	EZH2	T	0.30	0.00	0.007	0.07	0.06	0.08	0.12	0.63
rs28469012	CPXM2	T	0.05	0.45	0.003	0.04	0.10	0.10	0.12	0.04	1.81 [1.03–3.18]
rs10894768	IGSF9B	G	0.50	0.05	0.001	0.35	0.28	0.36	0.27	0.04	0.70 [0.49–0.99]
rs60252902	DHX37	A	0.30	0.00	0.007	0.11	0.11	0.09	0.07	0.76
rs3742130	GPR18	A	0.55	0.05	0.0005	0.26	0.27	0.23	0.19	0.80
rs9919887	SYNE3	G	0.05	0.45	0.003	0.20	0.16	0.20	0.19	0.43
rs2230434	ITGAL	T	0.00	0.25	0.01	0.11	0.09	0.09	0.07	0.32
rs2070896	ITGAX	C	0.56	0.05	0.0006	0.37	0.38	0.33	0.32	0.85
rs35299026	HSD17B14	A	0.25	0.00	0.01	0.05	0.07	0.05	0.06	0.31
rs10423927	NLRP9	G	0.25	0.00	0.01	0.11	0.06	0.08	0.06	0.09	0.58 [0.31–1.09]
rs2254562	SYNJ1	C	0.05	0.45	0.003	0.30	0.29	0.29	0.35	0.65

The minor allele frequencies (MAF) and uncorrected p values for each SNP selected from the discovery cohort are presented. For validation, heterogeneity tests and subsequent meta-analysis was performed in the two replication cohorts whenever possible. MAF and joint p values (calculated with Mantel-Haenszel test) are depicted for each SNP. In addition, odds ratio (OR) with their corresponding 95% confidence intervals (95% CI) are presented for SNPs with statistically significant results. *For SNP rs2374639, validation cohorts cannot be meta-analyzed due to high heterogeneity (I² = 80%, p = 0.03). On a separate analysis, the first validation cohort shows replication of the effect observed in the discovery cohort, with a lower frequency of the minor allele in aggressive MS compared to benign MS [p = 0.04, OR = 0.47 (0.23–0.95)]. The second validation cohort shows an increased frequency of the minor allele in aggressive MS that is not statistically significant [p = 0.39, OR = 1.22 (0.77–1.94)]

ISSN: 1742-2094