Table 4. EWAS database enrichments.

Ten strongest enrichments within the MRC-IEU EWAS database. FDR is the FDR-corrected P values from a Fisher’s exact test. Effect directions indicate whether the ALS EWAS and trait EWAS effect sizes share the same direction of effect (for example, an opposite direction of effect for BMI indicates that DNA methylation changes at overlapping positions associated with a lower BMI are also associated with a higher ALS risk). EWAS method indicates whether DMPs identified with respective method were enriched for the given trait.

Trait	FDR	Effect directions	EWAS method
BMI	1.36 × 10−9	Opposite	LB and MOA
Total serum IgE	1.93 × 10−7	Opposite	LB
Triglycerides	4.02 × 10−7	Opposite	LB and MOA
Serum triglycerides*	1.32 × 10−5	Opposite	LB and MOA
Waist circumference	1.85 × 10−4	Opposite	LB and MOA
HDL-c	0.0013	Equal	LB and MOA
Hypertriglyceridemic waist	0.0024	Equal	LB and MOA
Serum HDL-c*	0.0066	Equal	LB and MOA
Fasting glucose	0.0097	Opposite	LB and MOA
Atrial fibrillation	0.011	Opposite	LB and MOA

^*Note that we adhered to the trait descriptions as provided in the database: serum, plasma, and whole-blood measurements are included as distinct traits (“triglycerides” and “high-density lipoprotein cholesterol” refer to whole-blood measurements).