Fig. 1

Flowchart displays the selection process for instrumental variables of T2D to investigate the causal effect of T2D on ALS in the Mendelian randomization analysis. A: a set of index SNPs (p < 5.00E−8) were selected to ensure the relevance assumption was satisfied; we further used the F statistic [46, 47] to examine the strength of those index SNPs. B1: following previous studies [48], we attempted to exclude pleiotropic associations by removing index SNPs which were likely associated with ALS with a marginal p value less than 1.00E−5 (the genome-wide suggestive significance level); no index SNPs were removed by this strategy in our analysis; B2: we removed index SNPs which may potentially be in linkage disequilibrium with ALS-associated loci (identified in [49], Additional file 1: Table S7), if the index SNP position was within 1 Mb of an ALS-associated locus. C: similar to B2, based on previous GWAS results of lipid traits [50, 51], we removed index SNPs that were associated with lipids, since dyslipidemia may be linked to both T2D and ALS [45, 52,53,54]