PICALO: principal interaction component analysis for the identification of discrete technical, cell-type, and environmental factors that mediate eQTLs.

"the code version used for the manuscript as well as any custom code is available at https://doi org/10 5281/zenodo 8172196 [ 72 ]. availability of data and materials the raw rna-seq data of bios can be obtained from the european genome-phenome archive (ega; accession egas00001001077"

"the code for picalo and an animated explanation of the method are available at https://github com/molgenis/picalo .; the picalo software is available at https://github com/molgenis/picalo [ 71 ] under the bsd 3-clause "new" or "revised" license."

"Declarations Ethics approval and consent to participateAll cohorts included in this study enrolled participants with informed consent and collected and analyzed data in accordance with ethical and institutional regulations. The information about individual institutional review board approvals is available in the original publications for each cohort. Where applicable, data access agreements were signed by the investigators prior to the acquisition of the data, either to the UMCG (BIOS, AMP-AD, CMC, GTEx, CMC_HBCC, BrainSeq, UCLA_ASD, BrainGVEX, BipSeq, NABEC) or Biogen (TargetALS) which state the data usage terms. To protect the privacy of the participants, data access was restricted to the investigators of this study, as defined in those data access agreements. Per data use agreements, only summary-level data is made publicly available and strictly mentioned in the disclaimer that they cannot be used to re-identify study participants. Consent for publicationNot applicable. Competing interestsE.T. and H.R. are full-time employees and hold stock options at Biogen. The remaining authors declare that they have no competing interests. Competing interests E.T. and H.R. are full-time employees and hold stock options at Biogen. The remaining authors declare that they have no competing interests."

"Funding P.D. is supported by an NWO, ZonMW-VENI grant (no. 9150161910057). E.A.T. and H.R. are employed by Biogen. J.F. is supported by the Dutch Heart Foundation IN-CONTROL (CVON2018-27), the ERC Consolidator grant (grant agreement No. 101001678), NWO-VICI grant VI.C.202.022, the AMMODO Science Award 2023 for Biomedical Sciences from Stichting Ammodo, and the Netherlands Organ-on-Chip Initiative, an NWO Gravitation project (024.003.001) funded by the Ministry of Education, Culture and Science of the government of the Netherlands. A.Z. is supported by an NWO Gravitation grant ExposomeNL 024.004.017 and EU Horizon Europe Program grant INITIALISE (101094099). L.F. is supported by a grant from the Dutch Research Council (ZonMW-VICI 09150182010019 to L.F.), an Oncode Senior Investigator grant, and a sponsored research collaboration with Biogen."