Micronutrient GWAS Synthesis and Analysis

We searched for published GWASs evaluating individuals of European ancestry on the GWAS Catalog and PubMed (the last search was performed in May 2022). We did not find any GWAS conducted for vitamins B1, B2, B3, B5, B7, sulfur, iodine, chloride, and fluoride. The GWASs conducted for vitamin K, potassium, sodium, cobalt, chromium, and molybdenum were excluded because of no significant genome-wide results [8 (link), 18 (link), 19 (link)]. In total, fourteen micronutrients of potential interest were identified: calcium [5 (link)], copper [6 (link)], iron [7 (link)], magnesium [8 (link)], selenium [6 (link)], zinc [6 (link)], beta-carotene [9 (link)], folate [10 (link)], vitamin A [11 (link)], vitamin B6 [12 (link)], vitamin B12 [10 (link)], vitamin C [13 (link)], vitamin D [14 (link)], and vitamin E [15 (link)] (Additional file 2: Additional Text) [5 (link)–15 (link), 20 , 21 (link)]. For copper, we also identified a more recent and larger GWAS by Jäger et al. [20 ], but given that this study reported Z-scores and not beta-coefficients, we used the study by Evans et al. [6 (link)] in order to improve interpretability. However, the genetic instruments from the GWAS by Jäger et al. [20 ] were used in secondary analyses. Vitamin A and vitamin E were excluded because those GWASs were adjusted for body mass index (BMI) [22 (link)] which might introduce collider bias if the genetic instruments of the exposure of interest also have an effect on BMI [23 (link)].
For the main MR analysis, we included independent SNPs (r² < 0.001 within 10,000-kb windows), strongly associated (P ≤ 5E−08) with the blood level of each micronutrient.