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PubMed2025

A genome-wide association study of methamphetamine use among people with HIV.

BACKGROUND: Amphetamine-like stimulants are the most used psychostimulants in the world; methamphetamine use is the most prevalent in people with HIV. Prolonged methamphetamine use can cause lasting damage to the heart, gut, and brain, as well as auditory hallucinations and paranoid thinking. However, relatively little is known about methamphetamine use and its genetic contributors. METHODS: Using genetic information from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort, we conducted a multi-ancestry genome-wide association study (GWAS) of methamphetamine use among people with HIV (n = 1,196 reported ever use, n = 4,750 reported never use). RESULTS: No single nucleotide polymorphism was statistically associated with methamphetamine use at the genome-wide level (p < 5 * 10-8) in our study. Further, we did not replicate previously suggested genetic variants from other studies (all p > 0.05 in our analysis). DISCUSSION: Our study suggests that there is no single strong genetic contributor to lifetime use of methamphetamine in people with HIV enrolled in CNICS. Larger studies with more refined outcome assessment are warranted to further understand the contribution of genetics to methamphetamine use and use disorder. Investigation into social and environmental contributors to methamphetamine use are similarly necessary.

Humans↗

PubMed2025

GWAS highlights the neuronal contribution to multiple sclerosis susceptibility.

Multiple Sclerosis (MS) is a chronic inflammatory and neurodegenerative disease affecting the brain and spinal cord. Genetic studies have identified many risk loci, that were thought to primarily impact immune cells and microglia. Here, we performed a multi-ancestry genome-wide association study with 20,831 MS and 729,220 control participants, identifying 236 susceptibility variants outside the Major Histocompatibility Complex, including four novel loci. We derived a polygenic score for MS and, optimized for European ancestry, it is informative for African-American and Latino participants. Integrating single-cell data from blood and brain tissue, we identified 76 genes affected by MS risk variants. Notably, while T cells showed the strongest enrichment, inhibitory neurons emerged as a key cell type. The expression of IL7 and STAT3 are affected only in inhibitory neurons, highlighting the importance of neuronal and glial dysfunction in MS susceptibility.

Journal Article↗

PubMed2026

Freely available genomic datasets for atrial fibrillation research: current resources and analytical pipeline.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, characterized by clinical and genetic heterogeneity. Increasing use of genomics and other omics approaches has driven reliance on publicly available AF datasets to advance biological discovery. Thus, this systematic review aimed to identify freely available genomic AF datasets through Mendeley Data and its interconnected repositories, and to characterize the most common analyses performed on these data. The search was conducted in adherence to the PRISMA 2020 guideline. Nineteen freely available genomic AF datasets were identified: Summary statistics for 'Biobank-driven genomic discovery yields new insight into atrial fibrillation biology', hum0014.v8.58qt.v1, AF GWAS in UK Biobank, UK Biobank (Publication 9659), GWAS summary statistics from a 2025 multi-ancestry AF meta-analysis, GSE115574, GSE128188, GSE14975, GSE2240, GSE238242, GSE254133, GSE261170, GSE271748, GSE271839, GSE293813, GSE294456, GSE31821, GSE41177, and GSE79768. The GEO datasets were further examined using differential gene expression, functional enrichment, protein-protein interaction networks, hub gene analysis, microRNA target prediction, and gene clustering, as well as, for the more recently deposited datasets, eQTL colocalization, single-cell/single-nucleus clustering, cell-cell communication analysis, and gene-dosage-dependent transcriptional and electrophysiological profiling. These analyses show some consistency but also considerable heterogeneity in initial conditions, data normalization, and analytical methodological settings. In conclusion, only a limited number of datasets are freely available, so additional, well-characterized and standardized datasets are needed to provide a complete picture of the AF pathology.

Mendeley Data↗

PubMed2026

Genomic basis of developmental defects of enamel and sex-specific effects.

We conducted a multi-ancestry genome-wide association study (GWAS) of developmental defects of enamel (DDE) in the primary dentition among 6,061 U.S. preschool-aged children (3-5 years). We investigated four DDE phenotypes (demarcated opacities, diffuse opacities, hypoplastic defects, and a combined DDE trait) leveraging main-effect models, joint gene-sex interaction testing (2df), and sex-stratified analyses. SNP-based heritability for the combined DDE trait was estimated at 20%, with concordance analyses robustly supporting a genetic etiology. We identified 39 unique genome-wide significant loci (P<5×10 ), with five surpassing a study-wide Bonferroni-corrected statistical significance criterion (P<1.25×10 9), including Y RNA and ALDH1A1. The main-effect GWAS identified 20 loci, including HBS1L and MYB, genes regulating hematopoiesis with plausible roles in amelogenesis. Joint test and sex-stratified analyses revealed 19 additional loci, including ALDH1A1, TENM2, and DLGAP2, demonstrating sex-specific heterogeneity. Nineteen loci exhibited sex-specific differences after Bonferroni correction (P<2x10-3), including genes involved in retinoic acid signaling (ALDH1A1), odontogenesis (TENM2), and neurodevelopment (DLGAP2, CDH10). Pathway enrichment highlighted ectodermal and synapse organization networks, suggesting shared etiological mechanisms between DDE and systemic conditions like neurofibromatosis and autism spectrum disorder. Notably, no locus generalized in an external GWAS of permanent dentition DDE, underscoring fundamental biological differences in the genetic architectures governing primary versus permanent enamel formation. Crucially, a comprehensive cross-trait pleiotropy lookup against early childhood caries (ECC) revealed no shared genetic architecture, supporting the notion that the established clinical and epidemiological association between DDE and ECC is likely driven by structural defects increasing caries lesion susceptibility rather than genetic pleiotropy. By integrating gene-sex interaction testing, this study offers novel insights into the complex, sexually dimorphic genetic etiology of DDE and augments the biological evidence base that can support the development of precision pediatric dentistry.

developmental defects of enamel↗

PubMed2024

Genome-wide association study of the common retinal disorder epiretinal membrane: Significant risk loci in each of three American populations.

Epiretinal membrane (ERM) is a common retinal condition characterized by the presence of fibrocellular tissue on the retinal surface, often with visual distortion and loss of visual acuity. We studied European American (EUR), African American (AFR), and Latino (admixed American, AMR) ERM participants in the Million Veteran Program (MVP) for genome-wide association analysis-a total of 38,232 case individuals and 557,988 control individuals. We completed a genome-wide association study (GWAS) in each population separately, and then results were meta-analyzed. Genome-wide significant (GWS) associations were observed in all three populations studied: 31 risk loci in EUR subjects, 3 in AFR, and 2 in AMR, with 48 in trans-ancestry meta-analysis. Many results replicated in the FinnGen sample. Several GWS variants associate to alterations in gene expression in the macula. ERM showed significant genetic correlation to multiple traits. Pathway enrichment analyses implicated collagen and collagen-adjacent mechanisms, among others. This well-powered ERM GWAS identified novel genetic associations that point to biological mechanisms for ERM.

Humans↗

PubMed2025

Identification of novel type 1 and type 2 diabetes genes by co-localization of human islet eQTL and GWAS variants with colocRedRibbon.

Over 1,000 genetic variants have been associated with diabetes by genome-wide association studies (GWASs), but for most, their functional impact is unknown; only 7% alter gene expression in pancreatic islets in expression quantitative trait locus (eQTL) studies. To fill this gap, we developed a co-localization pipeline, colocRedRibbon, that prefilters eQTLs by the direction of effect on gene expression and shortlists overlapping eQTL and GWAS variants prior to co-localization. Applying colocRedRibbon to recent diabetes and glycemic trait GWASs, we identified 292 co-localizing gene regions, including 24 co-localizations for type 1 diabetes and 268 for type 2 diabetes and glycemic traits, representing a 4-fold increase. A low-frequency type 2 diabetes protective variant increases islet MYO5C expression, and a type 1 diabetes protective variant increases FUT2 expression. These novel co-localizations advance the understanding of diabetes genetics and its impact on human islet biology. colocRedRibbon has broad applicability to co-localize GWASs and various QTLs.

Humans↗