Genome-wide association study of major anxiety disorders in 122,341 European-ancestry cases identifies 58 loci and highlights GABAergic signaling DOI
Nora I. Strom, Brad Verhulst, Silviu‐Alin Bacanu

et al.

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

Published: July 5, 2024

Abstract The major anxiety disorders (ANX; including generalized disorder, panic and phobias ) are highly prevalent, often onset early, persist throughout life, cause substantial global disability. Although distinct in their clinical presentations, they likely represent differential expressions of a dysregulated threat-response system. Here we present genome-wide association meta-analysis comprising 122,341 European ancestry ANX cases 729,881 controls. We identified 58 independent significant risk variants 66 genes with robust biological support. In an sample 1,175,012 self-report 1,956,379 controls, 51 the associated were replicated. As predicted by twin studies, found genetic correlation between depression, neuroticism, other internalizing phenotypes. Follow-up analyses demonstrated enrichment all brain regions highlighted GABAergic signaling as one potential mechanism underlying risk. These results advance our understanding architecture prioritize for functional follow-up studies.

Language: Английский

Pervasive biases in proxy genome-wide association studies based on parental history of Alzheimer’s disease DOI
Yuchang Wu, Zhongxuan Sun,

Qinwen Zheng

et al.

Nature Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 4, 2024

Language: Английский

Citations

6
Cross-disorder genetic analysis of immune diseases reveals distinct gene associations that converge on common pathways DOI Creative Commons

Pietro Demela,

Nicola Pirastu, Blagoje Soskic

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 12, 2023

Abstract Genome-wide association studies (GWAS) have mapped thousands of susceptibility loci associated with immune-mediated diseases. To assess the extent genetic sharing across nine diseases we apply genomic structural equation modelling to GWAS data from European populations. We identify three disease groups: gastrointestinal tract diseases, rheumatic and systemic allergic Although groups are highly specific, they converge on perturbing same pathways. Finally, test for colocalization between single-cell eQTLs derived peripheral blood mononuclear cells. causal route by which 46 predispose find evidence eight genes being candidates drug repurposing. Taken together, here show that different constellations distinct patterns associations, but nodes in T cell activation signalling

Language: Английский

Citations

15
Gene Discovery and Biological Insights into Anxiety Disorders from a Multi-Ancestry Genome-wide Association Study of >1.2 Million Participants DOI Open Access
Eleni Friligkou, Solveig Løkhammer, Brenda Cabrera‐Mendoza

et al.

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

Published: Feb. 15, 2024

ABSTRACT We leveraged information from more than 1.2 million participants to investigate the genetics of anxiety disorders across five continental ancestral groups. Ancestry-specific and cross-ancestry genome-wide association studies identified 51 anxiety-associated loci, 39 which are novel. Additionally, polygenic risk scores derived individuals European descent were associated with in African, Admixed-American, East Asian The heritability was enriched for genes expressed limbic system, cerebral cortex, cerebellum, metencephalon, entorhinal brain stem. Transcriptome- proteome-wide analyses highlighted 115 through brain-specific cross-tissue regulation. also observed global local genetic correlations depression, schizophrenia, bipolar disorder putative causal relationships several physical health conditions. Overall, this study expands knowledge regarding pathogenesis disorders, highlighting importance investigating diverse populations integrating multi-omics information.

Language: Английский

Citations

5
Combining Transdiagnostic and Disorder-Level GWAS Enhances Precision of Psychiatric Genetic Risk Profiles in a Multi-Ancestry Sample DOI Creative Commons
Yousef Khan, Christal N. Davis, Zeal Jinwala

et al.

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

Published: May 10, 2024

Abstract The etiology of substance use disorders (SUDs) and psychiatric reflects a combination both transdiagnostic (i.e., common) disorder-level independent) genetic risk factors. We applied genomic structural equation modeling to examine these factors across SUDs, psychotic, mood, anxiety using genome-wide association studies (GWAS) European-(EUR) African-ancestry (AFR) individuals. In EUR individuals, represented SUDs (143 lead single nucleotide polymorphisms [SNPs]), psychotic (162 SNPs), mood/anxiety (112 SNPs). identified two novel SNPs for that have probable regulatory roles on FOXP1 , NECTIN3 BTLA genes. AFR (1 SNP) (no significant SUD factor SNP, although previously in EUR- cross-ancestry GWAS, is finding Shared variance accounted overlap between their comorbidities, with second-order GWAS identifying up 12 not significantly associated either first-order Finally, common independent effects showed different associations psychiatric, sociodemographic, medical phenotypes. For example, the components schizophrenia bipolar disorder had distinct affective risk-taking behaviors, phenome-wide conditions tobacco broader factor. Thus, combining approaches can improve our understanding co-occurring increase specificity discovery, which critical demonstrate considerable symptom etiological overlap.

Language: Английский

Citations

5
Genome-wide association study of major anxiety disorders in 122,341 European-ancestry cases identifies 58 loci and highlights GABAergic signaling DOI
Nora I. Strom, Brad Verhulst, Silviu‐Alin Bacanu

et al.

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

Published: July 5, 2024

Abstract The major anxiety disorders (ANX; including generalized disorder, panic and phobias ) are highly prevalent, often onset early, persist throughout life, cause substantial global disability. Although distinct in their clinical presentations, they likely represent differential expressions of a dysregulated threat-response system. Here we present genome-wide association meta-analysis comprising 122,341 European ancestry ANX cases 729,881 controls. We identified 58 independent significant risk variants 66 genes with robust biological support. In an sample 1,175,012 self-report 1,956,379 controls, 51 the associated were replicated. As predicted by twin studies, found genetic correlation between depression, neuroticism, other internalizing phenotypes. Follow-up analyses demonstrated enrichment all brain regions highlighted GABAergic signaling as one potential mechanism underlying risk. These results advance our understanding architecture prioritize for functional follow-up studies.

Language: Английский

Citations

5