Tag

Gwas

All articles tagged with #gwas

health27 days ago•84 min saved

Brain-focused genes emerge as key drivers of fibromyalgia in a 2.5 million-person study

A multi-ancestry GWAS meta-analysis of 2.56 million individuals (54,629 cases; 2,509,126 controls) identified 26 fibromyalgia risk loci, led by a coding HTT variant; neural genes such as DCC, DRD2/NCAM1, MDGA2 and CELF4 highlight brain pathways as central to fibromyalgia. Heritability is enriched in brain tissues and neurons, with dentate gyrus neurons showing the strongest signal, supporting a CNS basis and possible gut–brain interactions via enteric neurons. Genetic correlations show widespread pleiotropy with chronic pain, psychiatric and metabolic traits, notably pain syndromes and PTSD. The genetic architecture is nearly identical in males and females, despite prevalence differences. Polygenic risk scores have modest predictive value (highest AUC ~0.59 in Europeans) and can stratify risk. Therapeutic implications include HTT/GPR52 and CELF4 targets, arguing against a primary autoimmune etiology. Limitations include predominantly European ancestry and ICD-based phenotyping; replication in diverse groups is needed. Overall, findings map fibromyalgia to central nervous system biology and provide molecular entry points for future research.

via Nature|

#brain #fibromyalgia #genetics

science1 month ago•6 min saved

Largest GWAS uncovers first genetic risk clues for borderline personality disorder

A large, multi-study genome-wide association analysis of European- ancestry participants identified 11 genomic loci linked to borderline personality disorder, with nine nearby functional genes. Replication supported five additional loci, bringing the total to 11. The newly identified variants account for about 17% of inherited risk, indicating genetics play a meaningful but partial role in BPD.

via Nature|

#borderline-personality-disorder #genetics #gwas

science1 month ago•6 min saved

Study uncovers two biologically distinct forms of major depression tied to energy symptoms

A preprint analyzing energy-related symptoms (AERS) splits major depressive disorder into two biologically distinct subtypes: AERS+ (hypersomnia with weight gain) and AERS- (insomnia with weight loss), plus an uncategorized middle group, based on three genome-wide association meta-analyses in over 460,000 individuals of European ancestry. The study identifies 27 genetic loci and shows divergent genetic architectures: AERS+ links to metabolic syndrome, obesity, inflammation, and comorbidities, while AERS- links to excitatory neurons and other metabolic traits. An immunometabolic framework suggests metabolic and inflammatory pathways may modify, rather than cause, subtypes, offering insight into symptom variability and personalized treatment; the work is a preprint, not yet peer-reviewed.

via ScienceAlert|

#aers #gwas #immunometabolic

science1 month ago•14 min saved

Genome-wide analysis links 74 anxiety-associated loci, 39 of them novel

A GWAS of 693,869 individuals found 74 loci tied to anxiety symptom severity—the most in a single study, with 39 novel associations. By treating anxiety as a dimensional trait rather than a binary diagnosis, the study preserved more genetic signal and revealed a highly polygenic architecture with many small effects, including strong signals near brain-expressed genes PCLO and SORCS3. Some loci overlap genetically with heart disease, gut disorders, and migraines, suggesting shared biology. Common variants explain about 6% of anxiety-severity variation, and polygenic scores account for up to ~3% in individuals, far from predictive power, but the map provides concrete targets for biology-driven drug development and future functional studies.

via Space Daily|

#anxiety #genetics #gwas

science1 month ago•95 min saved

Genetics link infant temperament to later behavior across diverse populations

This GWAS meta-analysis across European and multi-ancestry cohorts (up to ~78k infants) identifies ten loci associated with four temperament traits in the first three years: emotionality, activity, shyness, and sociability. SNP heritability ranges from ~3% to ~15%, two loci colocalize with adult cortex eQTLs (RHEBL1 and MR1), and genetic correlations link early temperament to adult neuroticism, ADHD, autism and extraversion. Findings replicate across ancestry groups, and polygenic scores explain modest variance, with within-family analyses supporting genetic influences on temperament.

via Nature|

#genetics #gwas #infancy

science2 months ago•14 min saved

Genome-wide study links anxiety severity to gut-brain axis and shared genetics with heart disease

A large, continuous-spectrum GWAS of anxiety symptoms (693,869 European-ancestry participants) identified 74 genetic loci (39 new) and revealed notable genetic overlap with irritable bowel syndrome (r≈0.57) and modest overlaps with coronary artery disease and migraine. The study estimates about 6% of anxiety symptom variation is explained by common variants, with the rest shaped by environment and gene–environment interactions; researchers caution that correlations do not imply causation and emphasize methodological advances (dimensional analysis) and the need for more diverse datasets. It complements clinically diagnosed anxiety genetics work and highlights gut–brain axis as a key area for future research.

via Space Daily|

#anxiety #genetics #gut-brain-axis

science2 months ago•78 min saved

Single-cell atlas links IBD risk to cell-type specific gene regulation

Researchers built IBDverse, the largest single-cell eQTL atlas for inflammatory bowel disease, mapping cis-eQTL effects across blood and gut tissues in about 400 individuals to link genetic risk to specific cell types. They find cell-type eQTLs are more distal, enhancer-rich, and far more likely to colocalize with IBD GWAS signals than bulk-tissue eQTLs, nominating effector genes such as MAML2 and ZMIZ1 in dendritic cells and MYC and RASGRP1 in colonocytes. Notch pathway regulators in dendritic cells and Wnt-driven epithelial renewal in colonocytes emerge as key mechanisms, tying regulatory variation to barrier dysfunction and inflammation. The study also highlights therapeutic angles—including PRKCB inhibitors and targets like ITGA4/JAK2—and provides a framework for interpreting GWAS loci via cell-type–resolved eQTL mapping in complex diseases.

via Nature|

#eqtl #gwas #ibd

science2 months ago•88 min saved

Consensus GWAS uncovers 91 ADRD risk loci and ties polygenic risk to Alzheimer’s pathology

A European-ancestry meta-analysis of ADRD GWAS (128,681 cases/proxy; 849,833 controls) identified 91 genome-wide loci, including 16 new ones, with 56 loci influencing clinically diagnosed Alzheimer’s disease (18 tier-2 loci needing external validation). Excluding APOE, polygenic scores were linked to AD pathology: in top-decile individuals, Braak stage >4 and moderate/severe neuritic plaques at death were about 2× more likely, though overall predictive power is modest (roughly 4% of variance explained; small AUC gains). Results held across main, no-proxy, and no-biobank analyses and showed microglia enrichment and pathways tied to tau, amyloid, lipids, and immunity; genetic correlations connected ADRD with Lewy body dementia, ALS, PD and educational attainment. The authors call for larger well-characterized neuropathology datasets to clarify locus effects on AD pathology versus other dementias and provide further external validation for certain loci and no-proxy/no-biobank statistics for broader use.

via Nature|

#alzheimers-disease #genomics #gwas

genomics3 months ago•56 min saved

Massive GWAS maps 249 circulating metabolites to thousands of genetic signals in 619,372 individuals

A large GWAS meta-analysis of 249 circulating metabolic traits in the Estonian Biobank and UK Biobank (up to 619,372 individuals) identifies 88,127 locus–trait associations across 8,398 loci. Using fine mapping, phenome‑wide colocalization, and cis‑Mendelian randomization, the study highlights the value of low‑frequency variants (MAF 0.1–1%) in explaining heritability and points to causal links between metabolic traits and diseases such as CAD and T2D. Notably, 19.4% of confidently fine‑mapped variants are low‑frequency missense or splice variants, enriching interpretability. The work also uncovers three lactate‑related loci (GP6, GRK5, ZFPM2) where higher plasma lactate associates with pulmonary embolism risk, potentially reflecting platelet activation rather than a direct causal effect. Overall, integrating low‑frequency variation improves mapping precision and biological insight into metabolism and disease.

via Nature|

#colocalization #genomics #gwas

health10 months ago•3 min saved

Genetic and Biological Factors Underlying Sex Differences in Depression

A large genetics study reveals women have more genetic risk variants for major depressive disorder than men, with stronger links to metabolic traits, helping to understand sex-specific aspects of depression and guiding future treatments.

via Nature|

#depression #genetics #gwas

science10 months ago•5 min saved

Genetic Insights Connect Cannabis Use to Mental and Physical Health

A large genetic study by UC San Diego and 23andMe identified gene variants linked to cannabis use, revealing associations with psychiatric, cognitive, and physical health traits, which could inform prevention and treatment strategies for cannabis use disorder.

via UC San Diego Today|

#cannabis #genetics #gwas

science-and-research2 years ago•73 min saved

"Comprehensive Analysis of Circulating Metabolic Biomarkers Across the Genome"

A genome-wide association study involving 233 circulating metabolic traits in over 136,000 participants from 33 cohorts has identified more than 400 independent loci and assigned probable causal genes at two-thirds of these. The study highlights the importance of sample and participant characteristics on genetic associations and demonstrates substantial genetic pleiotropy for multiple metabolic pathways. Ancestry-stratified analyses show positive correlations across ethnic groups, and associations were strongly related to sample size. The study provides a foundational resource for examining the role of metabolism across diverse diseases and emphasizes the need for careful consideration of sample type and fasting status in interpreting results.

via Nature.com|

#genetic-associations #genome-wide-study #gwas

health-genetics2 years ago•105 min saved

Uncovering Genetic Markers Driving Type 2 Diabetes Heterogeneity

A study on type 2 diabetes (T2D) pathophysiology reveals genetic heterogeneity in T2D development and complications. The research, involving over 2.5 million individuals of diverse ancestry, identified 1,289 T2D association signals and classified them into eight mechanistic clusters based on their cardiometabolic profiles. The study also uncovered ancestry-correlated heterogeneity in allelic effects at T2D association signals, with differences in mean BMI in T2D cases and controls across ancestry groups playing a role. Additionally, the study tested the association of cluster-specific polygenic scores with T2D-related vascular outcomes, providing insights into the genetic drivers of T2D heterogeneity.

via Nature.com|

#diabetes #genetic-drivers #gwas

health-and-medicine2 years ago•35 min saved

"Exploring the Genetic Overlap Between Gestational Diabetes and Type 2 Diabetes"

A comprehensive genome-wide association study (GWAS) on Finnish women has nearly tripled the known genetic loci associated with gestational diabetes mellitus (GDM), identifying 13 distinct chromosomal regions and confirming a partially distinct genetic etiology from type 2 diabetes (T2D). The study found that while GDM shares some genetic predispositions with T2D, it also has unique genetic risk factors predominantly related to gestation. This research enhances the understanding of GDM's genetic underpinnings and suggests potential physiological mechanisms of glycemic control that are specific to pregnancy.

via Nature.com|

##finngenstudy #genetics

health2 years ago•52 min saved

Uncovering the Biology and Public Health Impact of Cannabis Use Disorder through Multi-Ancestry Study

A multi-ancestry genome-wide association study has identified 22 independent genome-wide significant loci associated with cannabis use disorder (CanUD) in European ancestry populations, as well as additional loci in African, Admixed American, and East Asian ancestries. The study also revealed genetic correlations between CanUD and various psychiatric and substance use disorder traits, as well as causal relationships with chronic pain, lung cancer, and schizophrenia. Additionally, transcriptome-wide association studies identified genes associated with CanUD in adult and fetal brain tissue, with fetal brain tissue showing greater enrichment for SNP-based heritability. The findings provide insights into the biology of CanUD and have implications for public health.

via Nature.com|

#cannabis-use-disorder #genetic-study #gwas