Genome-wide analysis identifies novel shared loci between depression and white matter microstructure

Molecular Psychiatry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 19, 2025

Depression, a complex and heritable psychiatric disorder, is associated with alterations in white matter microstructure, yet their shared genetic basis remains largely unclear. Utilizing the largest available genome-wide association study (GWAS) datasets for depression (N = 674,452) microstructure 33,224), assessed through diffusion tensor imaging metrics such as fractional anisotropy (FA) mean diffusivity (MD), we employed linkage disequilibrium score regression method to estimate global correlations, local analysis of [co]variant approach pinpoint genomic regions conjunctional false discovery rate identify variants. Our findings revealed that showed significant correlations FA 37 MD 59 regions, while were weak. Variant-level identified 78 distinct loci jointly (25 novel loci) (35 loci), 41 (17 loci). Further analyses these exhibited both concordant discordant effect directions between traits, well overlapping hemispheric patterns architecture. Enrichment implicated biological processes related metabolism regulation. This provides evidence mixed-direction architecture microstructure. The identification specific pathways offers potential insights developing targeted interventions improve integrity alleviate depressive symptoms.

Язык: Английский

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Novel mechanistic insights into the comorbidity of anemia and rheumatoid arthritis: Identification of therapeutic targets

Molecular Immunology, Год журнала: 2025, Номер 180, С. 74 - 85

Опубликована: Фев. 27, 2025

Язык: Английский

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Genetic and neural mechanisms shared by schizophrenia and depression

Molecular Psychiatry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 3, 2025

Язык: Английский

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Identification of genetic architecture shared between schizophrenia and Alzheimer’s disease

Translational Psychiatry, Год журнала: 2025, Номер 15(1)

Опубликована: Апрель 16, 2025

Both schizophrenia (SCZ) and Alzheimer's disease (AD) are highly heritable brain disorders. Despite of the observed comorbidity shared psychosis cognitive decline between two disorders, genetic risk architecture by SCZ AD remains largely unknown. Based on summary statistics currently available largest genome-wide association studies for (n = 130,644) 455,258) in individuals European ancestry, we conducted conditional/conjunctional false discovery rate (FDR) analysis to enhance statistical power discovering more associations with or detect common variants both We found conditioned vice versa across different levels significance, indicating polygenic overlap. 268 (78 novel) SCZ-only 125 (55 AD-only SNPs at conditional FDR < 0.01, 16 lead conjunctional 0.05. Only half showed concordant effect direction, which was consistent modest correlation (r 0.097; P 0.026) This study provides evidence overlap AD, suggesting existence molecular mechanisms, may inform therapeutic targets that applicable

Язык: Английский

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Brain connectivity and transcriptomic similarity inform abnormal morphometric similarity patterns in first-episode, treatment-naïve major depressive disorder

Journal of Affective Disorders, Год журнала: 2024, Номер 370, С. 519 - 531

Опубликована: Ноя. 9, 2024

Язык: Английский

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Causal relationships between hippocampal volumetric traits and the risk of Alzheimer’s disease: a Mendelian randomization study

Brain Communications, Год журнала: 2024, Номер 7(1)

Опубликована: Дек. 24, 2024

Abstract Alzheimer’s disease, a common and progressive neurodegenerative disorder, is associated with alterations in hippocampal volume, as revealed by neuroimaging research. However, the causal links between volumes of hippocampus its subfield structures disease remain unknown. A genetic correlation analysis using linkage disequilibrium score regression was conducted to identify volumetric traits linked disease. Following this, examine traits, we applied two-sample Mendelian randomization approach, utilizing bidirectional framework. Seven were found genetically correlated then included analyses. Inverse variance weighted analyses that increased left whole hippocampus, body, right presubiculum head cornu ammonis 1 causally related higher risks Conversely, risk decreased body hippocampus. These results validated through other approaches sensitivity analysis. Our findings uncover relationships suggesting not only potential significance these predicting but also reciprocal influence on volumes.

Язык: Английский

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Subcortical imaging-derived phenotypes are associated with the risk of Parkinson’s disease: A Mendelian Randomization Study

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Сен. 26, 2024

Background The abnormalities of subcortical structures, such as putamen and caudate, play a key role in the occurrence Parkinson’s disease (PD); however, whether how imaging-derived phenotypes (IDPs) structures are causally associated with risk PD remain poorly understood. Methods causal associations between IDPs from UK biobank were evaluated bidirectional two-sample Mendelian randomization (MR) studies. Results Totally five found to be PD. Among these IDPs, IDP 168 (Global volume gray matter, OR = 1.38 [1.16, 1.63], P 1.82 x 10^{− 4}), 214 (Right volume, 1.31 [1.15, 1.50], 7.71 5) 1441 (T2* signal right 1.21 [1.09, 1.35], 5.23 4) increased In contrast, 1358 (Mean intensity 0.72 [0.62, 0.85), 6.77 1344 left 0.76 [0.65, 0.88], 3.23 reduced Conclusions specific imaging features caudate altered developing PD, thereby providing new insights into development novel predictive biomarkers therapies for patients.

Язык: Английский

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