Fig. 2. EWAS database enrichments.

Significant overlap (Fisher’s exact test, FDR < 0.05) between traits included in the MRC-IEU EWAS database and ALS-associated positions identified using the LB model. (A) Network showing the traits that significantly (FDR < 0.05) overlap with the ALS-associated positions. Nodes indicate the overlap between ALS-associated positions and positions associated with indicated traits, with larger nodes indicating more overlap, and lighter shades of blue indicating stronger associations. Edges indicate probe overlap between the traits, with thicker lines indicating more overlapping probes. Colored surfaces indicate the clusters (cholesterol, metabolic, and inflammatory) identified using the Louvain clustering algorithm. (B) Identification of independent clusters of traits. The first iteration shows the traits that significantly overlap with the ALS-associated probes at FDR < 0.05. In subsequent iterations, the probes belonging to the trait with the lowest-enrichment P value were excluded, and enrichment tests were performed using the remaining traits. This algorithm was repeated, retaining traits that were nominally significant (P < 0.05, indicated in bold), until at most one trait remained nominally significant. At the third iteration, no traits remained nominally significant (P < 0.05), showing that both BMI and related traits (including triglycerides and HDL-c) and IgE and related traits (atopy) show independent overlap with the ALS-associated positions. IgE, total serum IgE; TG, triglycerides; sTG, serum triglycerides; WC, waist circumference; sHDL-c, serum HDL-c: HW, hypertriglyceridemic waist; FG, fasting glucose; AF, atrial fibrillation; BMIc, BMI change; PL, postprandial lipemia; GGT, gamma-glutamyl transferase; fINS, fasting insulin; AC, alcohol consumption per day; 2hINS, 2-hour insulin; ATP, atopy; sIgE, high serum IgE; pAN, plasma adiponectin; T2D, type 2 diabetes; CKD, chronic kidney disease; HOMA-IR, homeostatic Model Assessment of Insulin Resistance.