biostudies-literatureXu MMGuangdong Basic and Applied Basic Research FoundationBasic and Applied Basic Research Foundation of Guangdong ProvinceNational Natural Science Foundation of ChinaChina Postdoctoral Science FoundationGuangzhou Key Laboratory of Formula-Pattern of Traditional Chinese MedicineScientific Research Program by Traditional Chinese Medicine Bureau of Guangdong Provincee06032https://www.ebi.ac.uk/biostudies/studies/S-EPMC12499405biostudies-literatureUnknown12(37)Despite emerging evidence of altered brain region volumes and functional networks in major depression (MD), causal relationships remain unexplored. Here, using genetic variants related to human brain morphometry (n = 36778) and functional networks (n = 47276), bidirectional two-sample and multivariable Mendelian randomization (MR) is performed to systematically investigate causal relationships between 83 brain-wide volumes, 191 resting-state functional magnetic resonance imaging phenotypes, and MD to identify core brain region volumes and functional networks associated with MD onset. Unlike other severe psychiatric disorders, reductions in left and right ventral diencephalon and thalamus volumes, together with decreased functional connectivity between the precuneus, cuneus, or cingulate gyAdvanced science (Weinheim, Baden-Wurttemberg, Germany)Genetic Evidence Supporting a Role for Brain Region Volume and Functional Network Alterations in Major Depression.PMC124994052020A151511057182474370202310882021020100142022M7213588237431982205270824742078210498382174253Lv YWGuo YYu ZYChen XYYang WMZhang YMXu MMLi NfalseGenetic Evidence Supporting a Role for Brain Region Volume and Functional Network Alterations in Major Depression.Despite emerging evidence of altered brain region volumes and functional networks in major depression (MD), causal relationships remain unexplored. Here, using genetic variants related to human brain morphometry (n = 36778) and functional networks (n = 47276), bidirectional two-sample and multivariable Mendelian randomization (MR) is performed to systematically investigate causal relationships between 83 brain-wide volumes, 191 resting-state functional magnetic resonance imaging phenotypes, and MD to identify core brain region volumes and functional networks associated with MD onset. Unlike other severe psychiatric disorders, reductions in left and right ventral diencephalon and thalamus volumes, together with decreased functional connectivity between the precuneus, cuneus, or cingulate gy2025-01-01T00:00:00Z2025 Oct2026-06-04T04:45:53.206Z2026-05-05T03:12:34.871ZS-EPMC124994054064131810.1002/advs.202506032