The causal relationship between antisocial behavior and resting-state networks: a two- sample Mendelian randomization study DOI Creative Commons

Yixin Zhao,

Weilong Guo,

Jiansong Zhou

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 18, 2023

Abstract Background A growing body of evidence shows that antisocial behavior is associated with resting-state network alterations. However, the causality this association not clear. Therefore, we used Mendelian randomization (MR) to examine causal relationship between (ASB) and networks (RSNs). Methods Genome-wide studies summary data ASB in 85359 participants from Complex Trait Genetics lab were identify their general risk preference. Data 27744 subjects functional connectivity within (RSN-FC). 27397 structural (RSN-SC). The weighted median, inverse variance method, randomization-Egger methods for MR analysis estimate effect directional pleiotropy. Results GWAS respectively three combined samples, which contained 85359, adult European ancestry. suggested no significant RSNs. Conclusion Numerous have found a close correlation present did find direct RSNs, suggesting there might be some mediating influencing factors or complex indirect pathways circuits

Language: Английский

Causal relationship between resting-state networks and depression: a bidirectional two-sample mendelian randomization study DOI Creative Commons

Dongmiao Huang,

Yuelin Wu,

Jihui Yue

et al.

BMC Psychiatry, Journal Year: 2024, Volume and Issue: 24(1)

Published: May 29, 2024

Abstract Background Cerebral resting-state networks were suggested to be strongly associated with depressive disorders. However, the causal relationship between cerebral and disorders remains controversial. In this study, we aimed investigate effect of on using a bidirectional Mendelian randomization (MR) design. Methods Updated summary-level genome-wide association study (GWAS) data correlated obtained from meta-analysis European-descent GWAS Complex Trait Genetics Lab. Depression-related FinnGen involving participants European ancestry. Resting-state functional magnetic resonance imaging multiband diffusion brain performed measure structural connectivity in seven well-known networks. Inverse-variance weighting was used as primary estimate, whereas MR-Pleiotropy RESidual Sum Outliers (PRESSO), MR-Egger, weighted median detect heterogeneity, sensitivity, pleiotropy. Results total, 20,928 20,573 well depression-related 48,847 patients 225,483 controls analyzed. Evidence for limbic network found inverse variance–weighted (odds ratio, $$28.21$$ ; 95% confidence interval, $$3.32-239.54$$ $$\text{P}=0.002$$ ), SC LN not found(OR=1.0025; CI,1.0005-1.0046; P =0.012). No significant associations MR study. Conclusions These results suggest that genetically determined has may play critical role its neuropathology.

Language: Английский

Citations

4
NEK4: prediction of available drug targets and common genetic linkages in bipolar disorder and major depressive disorder DOI Creative Commons
Bin Gong,

Chenxu Xiao,

Yu Feng

et al.

Frontiers in Psychiatry, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 30, 2025

Background Bipolar disorder (BD) is a mental illness characterized by alternating episodes of elevated mood and depression, while major depressive (MDD) debilitating condition that ranks second globally in terms disease burden. Pharmacotherapy plays crucial role managing both BD MDD. We investigated the genetic differences populations individuals with MDD BD, from perspective, we offered new insights into potential drug targets. This will provide clues to Methods study employed genome-wide association studies (GWAS) summary-data-based Mendelian randomization (SMR) methods investigate underpinnings patients bipolar predict target genes. Genetic variants associated were identified through large-scale GWAS datasets. For utilized comprehensive meta-analysis comprising 57 cohorts Europe, North America, Australia, including 41,917 cases 371,549 controls European ancestry. dataset included type 1 2 diagnosed based on DSM-IV, ICD-9, or ICD-10 criteria standardized assessments. MDD, used data Howard DM et al., which integrated largest totaling 246,363 561,190 controls. The SMR approach, combined expression quantitative trait loci (eQTL) data, was then applied assess causal associations between these gene expression, aiming identify markers targets Furthermore, two-sample (TSMR) analyses performed explore links protein (pQTL) disorders. Results analysis revealed 41 druggable genes five appeared brain tissue blood eQTL datasets significantly risk. 45 found be analysis, three simultaneously NEK4 , common candidate for also high risk diseases may help differentiate BD. Specifically, showed strong (β brain=0.126, P FDR=0.001; βblood=1.158, FDR=0.003) brain=0.0316, FDR=0.022; βblood=0.254, FDR=0.045). Additionally, notably linked (βbrain=0.123, FDR=2.97E-05; βblood=1.018, FDR=0.002), but no significant 2.Moreover, TSMR four proteins (BMP1, F9, ITIH3, SIGIRR) affecting PSMB4 Conclusion Our as key (MDD), suggesting its biomarker differentiating subtypes. Using GWAS, SMR, approaches, multiple risk, providing basis These findings offer promising directions precision medicine novel therapeutic strategies health treatment.

Language: Английский

Citations

0
Unveiling causal relationships between tobacco use phenotypes and neuroimaging: Insights from bidirectional Mendelian randomization and bibliometric analysis DOI Creative Commons
Zhiyong Zhang, Longtao Yang,

H.R. Guan

et al.

Brain Research Bulletin, Journal Year: 2025, Volume and Issue: 223, P. 111277 - 111277

Published: Feb. 26, 2025

Language: Английский

Citations

0
Rapidly evolved genomic regions shape individual language abilities in present-day humans DOI Creative Commons
Lucas G. Casten, Tanner Koomar, Taylor R. Thomas

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 11, 2025

1 Summary Minor genetic changes have produced profound differences in cognitive abilities between humans and our closest relatives, particularly language. Despite decades of research, ranging from single-gene studies to broader evolutionary analyses[1, 2, 3, 4, 5], key questions about the genomic foundations human language persisted, including which sequences are involved, how they evolved, whether similar occur other vocal learning species. Here we provide first evidence directly linking rapidly evolved regions contemporary humans. Through extensive analysis 65 million years events over 30,000 individuals, demonstrate that Human Ancestor Quickly Evolved Regions (HAQERs)[5] - accumulated mutations after human-chimpanzee split specifically influence but not general cognition. These shape development by altering binding Forkhead domain transcription factors, FOXP2 . Strikingly, language-associated HAQER variants show higher prevalence Neanderthals than modern humans, been stable throughout recent history, convergent evolution across mammalian learners. An unexpected pattern balancing selection acting on these apparently beneficial alleles is explained their pleiotropic effects prenatal brain contributing birth complications, reflecting an trade-off capability reproductive fitness. By developing Evolution Stratified-Polygenic Score analysis, capabilities likely emerged before human-Neanderthal far earlier previously thought[3, 6, 7]. Our findings establish direct link ancient divergence present-day variation abilities, while revealing constraints continue development.

Language: Английский

Citations

0
Heritability of white matter in twins: A diffusion neuroimaging review DOI

Giovanni Videtta,

Chiara Colli, Letizia Squarcina

et al.

Physics of Life Reviews, Journal Year: 2024, Volume and Issue: 50, P. 126 - 136

Published: July 6, 2024

Language: Английский

Citations

3
Causal Associations between Functional/Structural Connectivity and Stroke: A Bidirectional Mendelian Randomization Study DOI Creative Commons
Yisong Wang, Longtao Yang, Jun Liu

et al.

Biomedicines, Journal Year: 2023, Volume and Issue: 11(6), P. 1575 - 1575

Published: May 29, 2023

Disruption of brain resting-state networks (RSNs) is known to be related stroke exposure, but determining causality can difficult in epidemiological studies. We used data on genetic variants associated with the levels functional (FC) and structural connectivity (SC) within 7 RSNs identified from a genome-wide association study (GWAS) meta-analysis among 24,336 European ancestries. The for its subtypes were obtained MEGASTROKE consortium, including up 520,000 participants. conducted two-sample bidirectional Mendelian randomization (MR) investigate relationship between FC SC subtypes. results showed that lower global mean limbic network higher risk any ischemic small vessel separately. Moreover, ventral attention default mode have positive causal large artery stroke, respectively. In inverse MR analysis, causally dorsal somatomotor FC, present provides support or different contrasting effects there combination injury compensatory physiological processes following stroke. Further studies are necessary validate our explain mechanisms.

Language: Английский

Citations

5
A multi-omics Mendelian randomization study identifies new therapeutic targets for alcohol use disorder and problem drinking DOI
Daniel B. Rosoff, Josephin Wagner, Andrew S. Bell

et al.

Nature Human Behaviour, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 11, 2024

Language: Английский

Citations

1
Exploring causal association between functional/structural connectivity and major depression disorder: A bidirectional Mendelian randomization study DOI
Huacong Liu,

Zhenyi Lai,

Yumeng Huang

et al.

Journal of Affective Disorders, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

Citations

1
Genetics of neuroanatomy DOI
Bernardo de A.P.C. Maciel, Martijn P. van den Heuvel, Rachel M. Brouwer

et al.

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 148 - 155

Published: July 26, 2024

Language: Английский

Citations

0
Bidirectional Mendelian randomization highlights causal relationships between circulating INHBC and multiple cardiometabolic diseases and traits DOI
Nellie Y. Loh, Daniel B. Rosoff, Rebecca C. Richmond

et al.

Diabetes, Journal Year: 2024, Volume and Issue: 73(12), P. 2084 - 2094

Published: Sept. 16, 2024

Human genetic and transgenic mouse studies have highlighted a potential liver-adipose tissue endocrine axis, involving activin C (Act-C) and/or Act-E ALK7, influencing fat distribution systemic metabolism. We investigated the bidirectional effects between circulating INHBC, which homodimerizes into Act-C, adiposity traits, insulin resistance, inflammation, cardiometabolic disease risk. Additionally, we examined if Act-C is an ALK7 ligand in human adipocytes. used Mendelian randomization vitro immortalized abdominal gluteal Circulating INHBC was causally linked to reduced lower-body fat, dyslipidaemia, increased risks of coronary artery (CAD) non-alcoholic fatty liver (NAFLD). Conversely, upper-body distribution, obesity, hypertriglyceridemia, subclinical type 2 diabetes positively impacted plasma levels. Mechanistically, atherogenic lipid profile may partly explain INHBC-CAD link, while inflammation hypertriglyceridemia how traits affect INHBC. Phenome-wide showed weak causal relationships higher impaired kidney function gout In adipocytes, recombinant activated SMAD2/3 signaling via suppressed lipolysis. summary, influences metabolism by activating adipose serve as drug target for dyslipidemia, CAD, NAFLD.

Language: Английский

Citations

0