{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T05:04:58Z","timestamp":1789275898056,"version":"build-2803163510"},"reference-count":61,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Cellular heterogeneity limits causal inference in complex diseases. We applied an established cell-type-stratified Mendelian randomization (csMR) framework, originally developed by Hao et al. (2024), to investigate whether lipid phenotypes affect kidney disease through distinct brain cell populations, extended by a proteome-wide mediation component. Methods: Using Bayesian colocalization (posterior probability of hypothesis 4 [PPH4], \u22650.8) and multidimensional instrumental variable selection, we evaluated cell-type-stratified MR-supported associations of five lipid traits across ten brain cell or tissue strata with kidney disease risk. Instrumental variables were derived from published genome-wide association studies and human brain single-cell expression quantitative trait locus (eQTL) maps. An exploratory proteomic mediation analysis using the Difference Method was performed with UKB-PPP as the discovery resource and deCODE as the external validation resource, with mediation signals interpreted as hypothesis-generating. For the primary csMR analysis, multiple testing was corrected separately within each lipid trait using a Bonferroni threshold of 3.33 \u00d7 10\u22124, corresponding to 150 cell\/tissue-by-outcome tests per lipid trait. Results: In csMR analyses, cholesterol-related lipids showed cell-type-stratified associations with kidney disease, most prominently in oligodendrocyte-related analyses (max \u03b2 on the log-odds scale = 1.025). LDL-related associations with broad chronic glomerular disease were most evident in excitatory neuron-related analyses. Dual-cohort proteomic analysis prioritized plasma proteins, including SNAP29 and ICAM4, as candidate protein-associated signals for exploratory mediation analysis. These findings represent genetic colocalization and Mendelian randomization-supported associations, not experimentally established mechanisms, and should be interpreted as hypothesis-generating. Conclusions: This study provides a cell-type-resolved genetic and proteomic association map linking lipid traits, brain cell strata, and kidney disease outcomes, offering hypotheses for future experimental validation.<\/jats:p>","DOI":"10.3390\/genes17091097","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T13:29:29Z","timestamp":1789133369000},"page":"1097","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-Omics Mendelian Randomization Maps Lipid-Related Brain Cell-Type Associations with Kidney Disease"],"prefix":"10.3390","volume":"17","author":[{"given":"Jiani","family":"Deng","sequence":"first","affiliation":[{"name":"Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100700, China"},{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boning","family":"Cao","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100700, China"},{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengjie","family":"Zheng","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100700, China"},{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinan","family":"Ai","sequence":"additional","affiliation":[{"name":"Diabetes Department of Integrated Chinese and Western Medicine, China-Japan Friendship Hospital, Beijing  100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoxian","family":"Wang","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100700, China"},{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China"},{"name":"Nephrology Diagnosis and Treatment Center, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, China"},{"name":"Department of Nephropathy, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, China-Japan Friendship Hospital, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ibror.2018.11.008","article-title":"The human hypothalamus in mood disorders: The HPA axis in the center","volume":"6","author":"Bao","year":"2019","journal-title":"IBRO Rep."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-Gonz\u00e1lez, M.A., Conde, S.V., Latorre, R., Th\u00e9bault, S.C., Pratelli, M., Spitzer, N.C., Verkhratsky, A., Tremblay, M., Akcora, C.G., and Hern\u00e1ndez-Reynoso, A.G. 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