Contexts, kin and cognition: Effects of living arrangements and family resources on the cognitive function of older adults in Vietnam

Social Science & Medicine · 2026-03-26

Deep Sequencing of 71 Candidate Genes to Characterize Variation Associated with Alcohol Dependence

UNC Libraries · 2026-02-10

BACKGROUND: Previous genomewide association studies (GWASs) have identified a number of putative risk loci for alcohol dependence (AD). However, only a few loci have replicated and these replicated variants only explain a small proportion of AD risk. Using an innovative approach, the goal of this study was to generate hypotheses about potentially causal variants for AD that can be explored further through functional studies. METHODS: We employed targeted capture of 71 candidate loci and flanking regions followed by next-generation deep sequencing (mean coverage 78X) in 806 European Americans. Regions included in our targeted capture library were genes identified through published GWAS of alcohol, all human alcohol and aldehyde dehydrogenases, reward system genes including dopaminergic and opioid receptors, prioritized candidate genes based on previous associations, and genes involved in the absorption, distribution, metabolism, and excretion of drugs. We performed single-locus tests to determine if any single variant was associated with AD symptom count. Sets of variants that overlapped with biologically meaningful annotations were tested for association in aggregate. RESULTS: No single, common variant was significantly associated with AD in our study. We did, however, find evidence for association with several variant sets. Two variant sets were significant at the q-value <0.10 level: a genic enhancer for ADHFE1 (p = 1.47 × 10^-5 ; q = 0.019), an alcohol dehydrogenase, and ADORA1 (p = 5.29 × 10^-5 ; q = 0.035), an adenosine receptor that belongs to a G-protein-coupled receptor gene family. CONCLUSIONS: To our knowledge, this is the first sequencing study of AD to examine variants in entire genes, including flanking and regulatory regions. We found that in addition to protein coding variant sets, regulatory variant sets may play a role in AD. From these findings, we have generated initial functional hypotheses about how these sets may influence AD.

Mapping the genetic landscape across 14 psychiatric disorders

JuSER Publikationsportal · 2026-01-01

Genome-wide association study of major anxiety disorders in 122,341 European-ancestry cases identifies 58 loci and highlights GABAergic signaling

Nature Genetics · 2026-02-01 · 2 citations

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

Race Against Time: Fluid Racial Identity and Trajectories of Mental Health from Adolescence to Midlife

SSRN Electronic Journal · 2026-01-01

Genetics of cannabis ever-use and frequency across ancestries implicate novel loci and brain-specific biology

medRxiv · 2026-04-27

Abstract Cannabis use is widespread, with genetic differences partly explaining variation in individual patterns of use. We performed the largest-to-date genome-wide association study (GWAS) meta-analysis of cannabis ever-use (N=736,322, 76% European ancestry) and various measures of frequency of use (N=269,160 cannabis users, 84% European ancestry). We identified 54 independent genome-wide significant loci for ever-use and 6 for frequency and show that the genetic architecture of ever-use, frequency, and cannabis use disorder (CUD) are overlapping but distinguishable. We identified 63 loci that were associated with common liability (‘ All-cannabis ’) to different cannabis use traits in European-ancestry individuals. Across analyses, we identified 75 unique loci that had not previously been implicated in cannabis use. Gene prioritization analyses identified 349 genes for ever-use, 5 genes for frequency of use, and 429 for All-cannabis , including previously identified and novel genes. We found enrichment of genetic signals for cannabis use in biologically meaningful categories and relevant human brain cell types, including excitatory neuronal populations. There were substantial genetic correlations between cannabis use and a range of psychiatric disorders and substance use traits, while cannabis polygenic scores were associated with increased risk of psychiatric disorders. Mendelian Randomization showed evidence for (bidirectional) causal associations between cannabis use and ADHD, bipolar disorder, schizophrenia and PTSD.

Geographic and social inequalities in public school proximity to active landfills in the U.S.

Environmental Sociology · 2025-07-13

Genome-wide association study of adolescent-onset depression

medRxiv · 2025-09-26 · 1 citations

Adolescent depression is a heritable psychiatric condition with rising global prevalence and severe long-term outcomes, yet its biological underpinnings remain poorly understood. We conducted the first genome-wide association study of adolescent-onset depression, comprising 102,428 cases (diagnosis or clinical symptom thresholds) and 286,911 controls, including diverse ancestries. Cross-ancestry meta-analysis identified 52 independent variants across 17 loci; European-only analysis found 61 variants at 29 loci, with a SNP-based heritability of 9.8%. Comparative analyses revealed two genes unique to adolescent-onset versus lifetime depression, enriched in neuronal subtypes, and two genes as potential drug repurposing targets. Polygenic scores were associated with adolescent-onset depression across ancestries, persistent depression trajectories, more severe outcomes, as well as reduced cortical volume, surface area and white matter integrity. Genetic correlation and Mendelian randomisation analyses support shared genetic liability and causal links with early puberty and modifiable health and behavioural risk factors. These findings uncover novel genetic loci and refine biological pathways underlying adolescent-onset depression, revealing age-specific mechanisms and early intervention opportunities.

Publisher Correction: Genome-wide association meta-analysis of childhood ADHD symptoms and diagnosis identifies new loci and potential effector genes

Nature Genetics · 2025-09-29 · 1 citations

Mapping the genetic landscape across 14 psychiatric disorders

Nature · 2025-12-10 · 44 citations

Psychiatric disorders display high levels of comorbidity and genetic overlap1,2, challenging current diagnostic boundaries. For disorders for which diagnostic separation has been most debated, such as schizophrenia and bipolar disorder3, genomic methods have revealed that the majority of genetic signal is shared4. While over a hundred pleiotropic loci have been identified by recent cross-disorder analyses5, the full scope of shared and disorder-specific genetic influences remains poorly defined. Here we addressed this gap by triangulating across a suite of cutting-edge statistical and functional genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders (1,056,201 cases). Using genetic association data from common variants, we identified and characterized five underlying genomic factors that explained the majority of the genetic variance of the individual disorders (around 66% on average) and were associated with 238 pleiotropic loci. The two factors defined by (1) Schizophrenia and bipolar disorders (SB factor); and (2) major depression, PTSD and anxiety (Internalizing factor) showed high levels of polygenic overlap6 and local genetic correlation and very few disorder-specific loci. The genetic signal shared across all 14 disorders was enriched for broad biological processes (for example, transcriptional regulation), while more specific pathways were shared at the level of the individual factors. The shared genetic signal across the SB factor was substantially enriched in genes expressed in excitatory neurons, whereas the Internalizing factor was associated with oligodendrocyte biology. These observations may inform a more neurobiologically valid psychiatric nosology and implicate targets for therapeutic development designed to treat commonly occurring comorbid presentations. Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.