Science AI Journal
Biochemistry, Genetics and Molecular Biology · Research topic

Open research questions in Genetic Associations and Epidemiology

106 unresolved questions extracted from the limitations and future-work sections of 785 Genetic Associations and Epidemiology papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Evaluation of circulating proteins as potential mediators of disease risk identified limited evidence for causal effects, although LPA emerged as a candidate protein associated with takotsubo cardiomyopathy and other ill-defined heart diseases.

    Beyond the Canonical Loci of Brugada Syndrome, Takotsubo Cardiomyopathy and Primary Pulmonary Arterial Hypertension · 2026 · DOI

  • BackgroundThe rare cardiovascular diseases of Brugada Syndrome, takotsubo Cardiomyopathy, and primary pulmonary arterial hypertension remain comparatively under-investigated despite their substantial morbidity and mortality.

    Beyond the Canonical Loci of Brugada Syndrome, Takotsubo Cardiomyopathy and Primary Pulmonary Arterial Hypertension · 2026 · DOI

  • Background: Opioid use disorder (OUD) is heritable, yet most genome-wide association studies (GWAS) have focused on European populations, leaving the genetic architecture of OUD in non-European populations underexplored.

    Genome-Wide Association Studies and Deep-Learning Functional Annotation of Opioid Use Disorder across Three Ancestries in the All of Us Research Program · 2026 · DOI

  • Instead, the precision of the genetic-correlation estimates was limited by the available imaging GWAS sample size, uncertainty in SNP-based heritability estimates, and the large number of regional comparisons.

    An Initial Genetic Correlation Analysis of Externalizing Behavior and Neuroimaging Phenotypes in the ABCD Cohort · 2026 · DOI

  • Significant allelic effects occurred at comparable rates across common, rare, and singleton variants, demonstrating that, within MPRA-measurable effects, population frequency carries limited information about per-variant regulatory impact.

    Massively parallel characterization and predictive modelling of neuronal regulatory variation · 2026 · DOI

  • Sex differences influence the incidence, timing, clinical presentation, and outcomes of cardiovascular disease (CVD), yet the molecular programs through which aging interacts with biological sex remain insufficiently understood.

    Sex-Dimorphic Aging of Cardiovascular Disease Genes: A Network-Based Multi-Omics Analysis · 2026 · DOI

  • We expand analyses beyond the nuclear genome and identify 3 mitochondrial pQTLs, including a common variant in MT-RNR1, associated with lower myelin protein zero (MPZ), identifying a potential novel mechanistic link for MT-RNR1s poorly understood role in hearing loss.

    Proteogenomic origins of disease in British South Asians · 2026 · DOI

  • While previous approaches have benchmarked individual methods such as genome-wide association studies (GWAS), rare variant burden testing, and quantitative trait locus (QTL)-informed Mendelian randomization, it remains unclear how best to integrate these signals for drug target discovery.

    Integration of genetic evidence to identify approved drug targets · 2026 · DOI

  • This difference may arise because CATaN 5 captures TF-GRN-based regulatory signal rather than chromatin accessibility, although the contribution of 6 GZMK/B ⁺ CD8 ⁺ T cells to RA heritability remains to be…

    CATaN maps gene regulatory programs that shape genetic risk across complex diseases · 2026 · DOI

  • BackgroundHypertension and type 2 diabetes (T2D) are two of the most frequently co-occurring long-term conditions, but their shared mechanisms are not fully understood, often being attributed to adiposity pathways.

    Genome-wide association studies identify shared mechanisms between hypertension and type 2 diabetes independent of adiposity · 2026 · DOI

  • While AQP8 (mapped to rs9935028 on chromosome 16) is expressed in the brain, its func[on in the CNS remains unclear 64. While a gene[c overlap between schizophrenia and smoking behavior has been demonstrated in studies applying the cond/conj FDR method72, 73, it remains unknown if shared gene[c factors with smoking ini[a[on are different among TRS and non-TRS pa[ents. However, the molecular mechanisms underlying the schizophrenia-smoking associa[on are not completely understood70.

    Genetic overlap between treatment-resistant schizophrenia and smoking initiation · 2026 · DOI

  • This study has several limitations, and the conclusions are only mechanism hypotheses based on dry experiments, which have not been verified by in vitro, in vivo, and clinical studies; their scientific robustness and applicability need further confirmation by subsequent research. First, the research methods have inherent limitations: all results were obtained through network toxicology database analysis and in vitro molecular docking simulation, lacking direct verification by in vitro cell experiments and in vivo animal experiments. The associations between some targets and pathways in public databases are insufficiently supported by experimental evidence, which renders the in vivo reliability and applicability of the research conclusions to be further confirmed. Second, the study design did not clarify the doseeffect and time-effect relationships of nicotine exposure, nor did it explore the associations between different nicotine exposure doses, exposure durations, depression risk, and core target/pathway activation levels, making it difficult to truly reflect the toxicological effects of nicotine exposure in complex real environments. Third, the technical methods have inherent defects; the completeness of the databases used and the accuracy of the analysis algorithms may affect the accuracy of the results, which may lead to the omission of some key pathogenic mechanisms.

    The effects of nicotine exposure on depression: An integrative analysis combining network toxicology, molecular docking, and Mendelian randomization · 2026 · DOI

  • Nevertheless, the role of common genetic variations within MAP2 in SCZ susceptibility remains to be elucidated.

    Association of MAP2 gene polymorphisms and altered expression with schizophrenia risk in a Chinese Han population · 2026 · DOI

  • While these traits are heritable, the genetic overlap between normal variation in activity levels and neuropsychiatric disorders that involve motor dysfunction such as schizophrenia and Parkinsons disease (PD) remains unexplored.

    Genetic overlap with schizophrenia and Parkinson's reveals psychomotor basis of physical activity · 2026 · DOI

  • By contrasting estimates for three different polygenicity measures for a variety of human traits, we illustrated that most variant contributions to heritable variance are much smaller than the largest one, and, more generally, that these contributions vary widely (also see 24,31).

    Principled measures and estimates of trait polygenicity. · 2026 · DOI

  • Given the significance of reproducibility in genetic association studies and the scarcity of data from Southern Europe, we performed a case-control replication study to test the hypothesis that ENPP1 variants and haplotypes are associated with severe obesity in the underexplored and high-risk Greek population.

    Replication Study of ENPP1 Variants and Haplotypes Associated with Severe Obesity in a Greek Adult Population · 2026 · DOI

  • Abstract The ENPP1 (Ectonucleotide pyrophosphatase/phosphodiesterase 1) gene, encoding a protein that negatively modulates insulin receptor activation, remains relatively understudied in obesity genetics.

    Replication Study of ENPP1 Variants and Haplotypes Associated with Severe Obesity in a Greek Adult Population · 2026 · DOI

  • Polygenic risk scores (PRS) improve progressively as genome-wide association studies (GWAS) increase in sample size and ancestral diversity, yet the effect of successive GWAS releases on individual PRS rankings remains poorly characterised.

    Characterising the Stability of Polygenic Risk Scores: implications for risk stratification · 2026 · DOI

  • While tabular foundation models with in-context learning (ICL) have shown strong sample efficiency in other domains, their effectiveness for genotype-to-phenotype prediction and their robustness to ancestry-driven effect heterogeneity remain unclear.

    Bridging Ancestry Gaps in Genomic Risk Prediction with Tabular Foundation Models · 2026 · DOI

  • Body mass index (BMI) reflects general adiposity, waist circumference (WC) and hip circumference (HC) indicate regional fat distribution, and total fat percentage (TFP) represents overall body fat composition, while their independent disease-risk contributions remain unclear.

    Unraveling the causal web of 4 adiposity indices and 92 multi-system outcomes: A body-wide Mendelian randomization study · 2026 · DOI

  • Abstract Background Cardiorespiratory fitness (CRF) is a common risk factor for cardiometabolic diseases, but the causal relation of CRF with chronic obstructive pulmonary disease (COPD) and its interplay with genetic risk remain unknown.

    Cardiorespiratory fitness, genetic susceptibility, and the risk of chronic obstructive pulmonary disease: findings from observational and two-sample bidirectional Mendelian randomisation analyses · 2026 · DOI

  • These exclusions, often driven by logistical challenges and lack of data, prevent systematic identification of population-enriched associations, such as the association of the missense variant at the CREBRF locus to BMI and type 2 diabetes discovered commonly occurring in Polynesian populations due to its rarity in global populations.

    Meta-analysis of over 8,000 individuals from Hawai'i and Samoa for genetic associations to cardiometabolic phenotypes · 2026 · DOI

  • In Alzheimer's disease (AD), clinical and pathological heterogeneity is well recognized, but genetic dissection is limited by a lack of well-powered cohorts with deep phenotypic characterization.

    Dissecting Alzheimer's disease heterogeneity by cross-trait polygenic prediction · 2026 · DOI

  • Future work should explore the potential for boosting the predictive power 493 of family models through (i) multivariate models that simultaneously encompass multiple 494 cognitive and behavioral phenotypes, and (ii) incorporation of additional genotypic, environmental 495 and biological features.

    Appraising familial prediction of proband outcomes in neurogenetic disorders · 2026 · DOI

  • and colocalization analysis. However, several should be acknowledged. Although all GWAS datasets were derived from European-ancestry populations, the findings may not be generalizable to other ancestral groups. The number of instrumental SNPs for gastric cancer was limited, which may have reduced the precision of the forward MR estimates. retrospective clinical analysis included only 45 individuals and did not provide independent validation of the MR findings. Therefore, larger and mechanistic investigations are needed to determine whether the inverse association observed here reflects a true biological relationship or a more complex pattern of bias and indirect effects. ancestry-matched epidemiological supplementary In addition, studies the Nevertheless, several limitations should be acknowledged. First, although our instrumental variables were selected from well-powered GWAS datasets, the number of SNPs for gastric cancer was relatively small, which may have reduced the precision of the forward MR estimates. Second, although all GWAS datasets included in the present analysis were derived from European-ancestry populations, the findings may not be interactions or medication-related directly generalizable to other ancestral groups. Third, MR analyses assume linearity and no interaction between genetic therefore, gene– variants and environmental exposures; environment (e.g., antihypertensive drugs) could not be fully evaluated in the present study. Finally, as with all MR analyses, horizontal pleiotropy and residual confounding cannot be completely excluded, although our sensitivity analyses suggested minimal influence. Future studies incorporating multi-ancestry GWAS data and integrative omics analyses (e.g., transcriptome- or methylation-based MR) are warranted to validate and further elucidate the underlying mechanisms. The retrospective clinical component of this study has important limitations. The sample size was very small, including only 45 individuals, which substantially limited statistical power and precision. The observed association between hypertension and gastric cancer was not statistically significant, and the confidence interval was wide. Therefore, this small observational dataset should be regarded as preliminary and descriptive, rather than as a confirmatory or validating cohort. Future studies with larger and better- characterized clinical populations are required to determine whether the direction observed in the MR analysis can be replicated at the phenotypic level.

    Bidirectional Mendelian randomization analysis of hypertension, coronary artery disease, and gastric cancer with supplementary clinical data · 2026 · DOI

Most-cited papers in Genetic Associations and Epidemiology

Most recent work

Find a gap in your own Genetic Associations and Epidemiology sub-topic

This page shows what the Genetic Associations and Epidemiology literature already flags as unresolved. To narrow it to your specific question, run the guided finder — it searches the gap library on demand and checks candidates against 250M+ OpenAlex works.

Open the Research Gap Finder →

Related topics in Biochemistry, Genetics and Molecular Biology

Gut microbiota and health
289 open questions
Single-cell and spatial transcriptomics
185 open questions
dental development and anomalies
121 open questions
Mitochondrial Function and Pathology
110 open questions
Human-Animal Interaction Studies
105 open questions
Genomics and Chromatin Dynamics
97 open questions
Inflammatory Bowel Disease
91 open questions
Extracellular vesicles in disease
91 open questions
106 open questions have been extracted from the limitations and future-work passages of 785 Genetic Associations and Epidemiology papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

Tools for your next paper

Gaps & Literature SearchFind open questions in any field — 120,000+ open gaps mined from our own library.Pre-CheckIs your paper ready? A Tier 1–5 acceptance probability in seconds.Journal FinderA ranked shortlist of target journals from a 17,500-venue index.Duplicate Publication CheckerCheck prior-publication & salami-slicing risk across 8 sources.Citation GeneratorFreeA DOI or title → APA, MLA, Vancouver, Chicago, BibTeX, RIS. No signup.Graphical Abstract MakerFreeTurn your findings into a colorblind-safe graphical abstract.

Compare the category — Honest roundups of the AI research tools, ours listed alongside the alternatives.

Command palette

Jump anywhere, run any action.