Exome Sequencing of 963 Chinese Families Identifies Novel Epilepsy Candidate Genes DOI Open Access

Yu Ma,

Ke Su,

Mingshan Zhou

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 11, 2024

Abstract Epilepsy, a prevalent neurodevelopmental disorder in children, is often accompanied by detrimental psychological consequences and other comorbidities. We performed exome sequencing on 963 patient-parent trios, revealing differences genetic epidemiology between Chinese European epilepsy cohorts. The diagnostic yield for known genes was 40%. Pathogenic variants were most commonly found SCN1A, KCNQ2, DEPDC5. Additionally, we identified 15 novel monogenic candidates at least two patients diagnosed with developmental epileptic encephalopathy, non-acquired focal epilepsy, or generalized including ADCY2, BCAR3, CDC45, CHRNG, CRTC2, CSMD1, CSMD2, KDM6B, KIF1B, PLEKHM3, PPP4R1, RASGRP2, SGSM2, SYNE1 , ZFHX3 . Aside from ADCY2 which implicated the GABAergic synapse pathway based KEGG analysis, these do not belong to pathways. Local field potential recordings zebrafish calcium imaging experiments validated associations 11 of genes, excluding those unsuitable functional analyses. Furthermore, that CRTC2 overexpression leads hippocampal neuronal hyperactivity using multi-electrode arrays electrophysiology. have documented first-line medications prescribed harboring candidate genes. This study expands our understanding underpinnings provides opportunities early diagnosis personalized medicine approaches.

Language: Английский

Familial confounding in the associations between maternal health and autism DOI Creative Commons
Vahe Khachadourian, Elias Arildskov, Jakob Grove

et al.

Nature Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

Evidence suggests that maternal health in pregnancy is associated with autism the offspring. However, most diagnoses pregnant women have not been examined, and role of familial confounding remains unknown. Our cohort included all children born Denmark between 1998 2015 (n = 1,131,899) their parents. We fitted Cox proportional hazard regression models to estimate likelihood each prenatal ICD-10 diagnosis, accounting for disease chronicity comorbidity, correlations sociodemographic factors. examined evidence using discordant sibling paternal negative control designs. Among 1,131,899 individuals our sample, 18,374 (1.6%) were diagnosed by end follow-up. Across 236 we tested (prevalence ≥0.1%), 30 significantly after factors, disorder correction multiple testing. This obstetric, cardiometabolic psychiatric disorders (for example, diabetes (hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.08-1.31) depression (HR 1.49, CI 1.27-1.75)), previously shown be autism. Family-based analyses provided strong observed associations. findings indicate pervasive associations offspring underscore these are largely attributable confounding.

Language: Английский

Citations

2
Morphological and genetic decoding shows heterogeneous patterns of brain aging in chronic musculoskeletal pain DOI
Lei Zhao,

Jiao Liu,

Wenhui Zhao

et al.

Nature Mental Health, Journal Year: 2024, Volume and Issue: 2(4), P. 435 - 449

Published: March 26, 2024

Language: Английский

Citations

10
Investigating the shared genetic architecture between depression and subcortical volumes DOI Creative Commons

Mengge Liu,

Lu Wang,

Yujie Zhang

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Sept. 2, 2024

Depression, a widespread and highly heritable mental health condition, profoundly affects millions of individuals worldwide. Neuroimaging studies have consistently revealed volumetric abnormalities in subcortical structures associated with depression. However, the genetic underpinnings shared between depression volumes remain inadequately understood. Here, we investigate extent polygenic overlap using bivariate causal mixture model (MiXeR), leveraging summary statistics from largest genome-wide association for (N = 674,452) 14 phenotypes 33,224). Additionally, identify genomic loci through conditional/conjunctional FDR analyses. MiXeR shows that traits share substantial proportion variants depression, 44 distinct identified by subsequent conjunctional analysis. These are predominantly located intronic regions (58.7%) non-coding RNA (25.4%). The 269 protein-coding genes mapped these exhibit specific developmental trajectories, expression level 55 linked to both volumes, 30 cognitive abilities behavioral symptoms. findings highlight architecture phenotypes, enriching our understanding neurobiological Depression people authors show brain identifying loci.

Language: Английский

Citations

7
Dissecting the genetic overlap between severe mental disorders and markers of cellular aging: Identification of pleiotropic genes and druggable targets DOI
Claudia Pisanu,

Donatella Congiu,

Anna Maria Meloni

et al.

Neuropsychopharmacology, Journal Year: 2024, Volume and Issue: 49(6), P. 1033 - 1041

Published: Feb. 24, 2024

Language: Английский

Citations

6
Shared genetic architecture of cortical thickness alterations in major depressive disorder and schizophrenia DOI

He Wang,

Qiyu Zhao,

Yijing Zhang

et al.

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2024, Volume and Issue: 135, P. 111121 - 111121

Published: Aug. 22, 2024

Language: Английский

Citations

6
The shared genetic risk architecture of neurological and psychiatric disorders: a genome-wide analysis DOI Creative Commons
Olav B. Smeland, Gleda Kutrolli, Shahram Bahrami

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: July 23, 2023

While neurological and psychiatric disorders have historically been considered to reflect distinct pathogenic entities, recent findings suggest shared pathobiological mechanisms. However, the extent which these heritable share genetic influences remains unclear. Here, we performed a comprehensive analysis of GWAS data, involving nearly 1 million cases across ten diseases disorders, compare their common risk biological underpinnings. Using complementary statistical tools, demonstrate widespread overlap even in absence correlations. This indicates that large set variants impact multiple but with divergent effect sizes. Furthermore, interrogation revealed range processes associated diseases, while consistently implicated neuronal biology. Altogether, study key etiological aspects, has important implications for disease classification, precision medicine, clinical practice.

Language: Английский

Citations

14
Genetic overlap between schizophrenia and cognitive performance DOI Creative Commons
Jianfei Zhang,

Hao Qiu,

Qiyu Zhao

et al.

Schizophrenia, Journal Year: 2024, Volume and Issue: 10(1)

Published: March 5, 2024

Abstract Schizophrenia (SCZ), a highly heritable mental disorder, is characterized by cognitive impairment, yet the extent of shared genetic basis between schizophrenia and performance (CP) remains poorly understood. Therefore, we aimed to explore polygenic overlap SCZ CP. Specifically, bivariate causal mixture model (MiXeR) was employed estimate ( n = 130,644) CP 257,841), conjunctional false discovery rate (conjFDR) approach used identify loci. Subsequently, functional annotation enrichment analysis were carried out on identified genomic The MiXeR analyses revealed that 9.6 K variants are associated with 10.9 for CP, which 9.5 these two traits (Dice coefficient 92.8%). By employing conjFDR, 236 loci jointly 139 novel traits. Within loci, 60 exhibited consistent effect directions, while 176 had opposite directions. Functional indicated mainly located in intronic intergenic regions, found be involved relevant biological processes such as nervous system development, multicellular organism generation neurons. Together, our findings provide insights into architecture suggesting common pathways mechanisms contributing both

Language: Английский

Citations

5
Analysis of Acupuncture Point Selection Patterns for Epilepsy Treatment in the Past 20 Years DOI

正涛 杨

Traditional Chinese Medicine, Journal Year: 2025, Volume and Issue: 14(01), P. 42 - 57

Published: Jan. 1, 2025

Language: Английский

Citations

0
Genome‐Wide Association Study Reveals Genetic Architecture of Common Epilepsies DOI Open Access

Sarita Thakran,

Debleena Guin, Priyanka Singh

et al.

Clinical Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

ABSTRACT Epilepsy, affecting approximately 50 million individuals worldwide, exhibits a genetic heritability of 32%. While several genes/loci associated with epilepsy have been identified through candidate and genome‐wide association studies (GWAS), exploration population‐specific markers remains underexplored. We conducted the first GWAS in north Indian population (~1500 samples) to identify variants/loci risk, validated using targeted next‐generation sequencing (NGS). Our revealed 30 variants across seven loci including six novel loci. Subtype analysis based on etiology seizure types, 57 11 loci, 10 which are novel. Gene‐set unveiled enrichment genes glutathione synthesis recycling regulation dopaminergic neuron differentiation pivotal pathophysiology. Furthermore, PRS significant contribution an R 2 0.00573. Additionally, NGS showed ~95% concordance GSA genotypes. study highlights rs17031055/4q31.3 (DCHS2), rs73182224/3q27.2 (DGKG), rs9322462/6q25.2 (CNKSR3), rs75328617/8q24.23 (RNU1‐35P), rs2938010/10q26.13 (CTBP2) rs11652575/17p11.2 (SLC5A10 ) risk. These findings offer valuable insights into landscape population, providing foundation for future exploratory studies.

Language: Английский

Citations

0
Genome-wide analysis identifies novel shared loci between depression and white matter microstructure DOI Creative Commons

Qiyu Zhao,

Shuo Wang,

Di Xiong

et al.

Molecular Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 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.

Language: Английский

Citations

0