Individual cohorts participating in the study followed the analysis plans as specified in our analysis cookbooks (https://github.com/molgenis/systemsgenetics/wiki/eQTL-mapping-analysis-cookbook-(eQTLGen); https://github.com/molgenis/systemsgenetics/wiki/eQTL-mapping-analysis-cookbook-for-RNA-seq-data; https://github.com/molgenis/systemsgenetics/wiki/QTL-mapping-analysis-cookbook-for-Affymetrix-expression-arrays) or with slight alterations as described in the Methods and Supplementary Note. Tools and source codes used for genotype harmonization, identification of sample mix-ups, eQTL mapping, meta-analyses and calculation of PGSs are available at https://github.com/molgenis/systemsgenetics/. Tools used for primary analyses were written in Java (v6, v7, v8; www.java.com). Plink v1.0.7 (https://zzz.bwh.harvard.edu/plink/) and v1.90 (https://www.cog-genomics.org/plink/1.9/) was used for clumping and pruning. Downstream analyses and plots were done with R (v3.4.4, v3.6.1, v4.0.0; https://cran.r-project.org/) using packages data.table v1.12 (https://cran.r-project.org/web/packages/data.table/), tidyverse v1.2.1 (https://cran.r-project.org/web/packages/tidyverse/), broom v0.5.1 package (https://cran.r-project.org/web/packages/broom/), pheatmap v1.0.12 package (https://cran.r-project.org/web/packages/pheatmap/), GeneOverlap v1.18.0 (https://bioconductor.org/packages/release/bioc/html/GeneOverlap.html). Power analyses were conducted by R package pwr v1.3–0 (https://cran.r-project.org/web/packages/pwr/). scRNA-seq analyses made use of Cell Ranger Single Cell Software Suite v3.0.2 (https://support.10xgenomics.com/single-cell-gene-expression/software/pipelines/latest/what-is-cell-ranger) and its implementation of STAR aligner. ToppGene web tool (https://toppgene.cchmc.org/) was used for some interpretative enrichment analyses, as well as GeneNetwork web tool (https://genenetwork.nl/). Decon2 framework was (https://github.com/molgenis/systemsgenetics/tree/master/Decon2) used for predicting cell counts in BIOS data. We formatted our cis-eQTLs into the BESD format using SMR (https://cnsgenomics.com/software/smr/#Overview).
Võsa U., Claringbould A., Westra H.J., Bonder M.J., Deelen P., Zeng B., Kirsten H., Saha A., Kreuzhuber R., Yazar S., Brugge H., Oelen R., de Vries D.H., van der Wijst M.G., Kasela S., Pervjakova N., Alves I., Favé M.J., Agbessi M., Christiansen M.W., Jansen R., Seppälä I., Tong L., Teumer A., Schramm K., Hemani G., Verlouw J., Yaghootkar H., Sönmez R., Brown A., Kukushkina V., Kalnapenkis A., Rüeger S., Porcu E., Kronberg J., Kettunen J., Lee B., Zhang F., Qi T., Hernandez J.A., Arindrarto W., Beutner F., Dmitrieva J., Elansary M., Fairfax B.P., Georges M., Heijmans B.T., Hewitt A.W., Kähönen M., Kim Y., Knight J.C., Kovacs P., Krohn K., Li S., Loeffler M., Marigorta U.M., Mei H., Momozawa Y., Müller-Nurasyid M., Nauck M., Nivard M.G., Penninx B.W., Pritchard J.K., Raitakari O.T., Rotzschke O., Slagboom E.P., Stehouwer C.D., Stumvoll M., Sullivan P., ‘t Hoen P.A., Thiery J., Tönjes A., van Dongen J., van Iterson M., Veldink J.H., Völker U., Warmerdam R., Wijmenga C., Swertz M., Andiappan A., Montgomery G.W., Ripatti S., Perola M., Kutalik Z., Dermitzakis E., Bergmann S., Frayling T., van Meurs J., Prokisch H., Ahsan H., Pierce B.L., Lehtimäki T., Boomsma D.I., Psaty B.M., Gharib S.A., Awadalla P., Milani L., Ouwehand W.H., Downes K., Stegle O., Battle A., Visscher P.M., Yang J., Scholz M., Powell J., Gibson G., Esko T, & Franke L. (2021). Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression. Nature genetics, 53(9), 1300-1310.