Genetic risk factors for severe and fatigue dominant long COVID and commonalities with ME/CFS identified by combinatorial analysis

Table 10 Assessing the effects of the SNX9 rs2025994 genotype on severe long COVID when controlling for the genotypes of the interacting SNPs rs6777173 (KLF15) and rs11072524 (RYR3)

KLF15 minor allele count	RYR3 minor allele count	SNX9 homozygous wild type odds (cases:controls)	SNX9 heterozygous odds (cases:controls)	EGA Odds ratio: SNX9 heterozygous vs. homozygous wild type (95% confidence interval)
0	0	0.46 (74:160)	0.89 (17:19)	1.93 (0.95–3.93)
0	1	2.48 (57:23)	0.70 (7:10)	0.28 (0.10–0.83)
1	0	0.43 (114:267)	0.28 (14:50)	0.66 (0.35–1.23)
1	1	0.63 (48:76)	0.24 (6:25)	0.38 (0.15–0.99)
2	0	0.66 (71:108)	0.21 (6:28)	0.33 (0.13–0.83)
2	1	0.49 (17:35)	0.38 (3:8)	0.77 (0.18–3.29)

We present comparisons for genotype combinations that are present in more than 10 patients (which excludes the 18 patients who are homozygous for the SNX9 minor allele). None of the EGA odds ratios for the individual comparisons are statistically significant after correcting for multiple testing. However, among patients who possess a copy of the minor allele at either interacting SNP, presence of the SNX9 minor allele consistently results in lower odds of disease relative to the homozygous wild type genotype (Fisher’s Exact Test p = 0.00047). Among patients who possess only wild type alleles for both interacting SNPs, presence of the SNX9 minor allele results in higher odds of disease relative to the homozygous wild type genotype, but the difference is not statistically significant (Fisher’s Exact Test p = 0.075)

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