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17 recordsLinked to original sources
PubMed2026

Genetic Association Between Sleep Traits and Vertigo Risk: A Two-sample Bidirectional Mendelian Randomization Study.

BACKGROUND: Observational studies suggest the potential association between sleep traits and vertigo; however, causal evidence remains limited. OBJECTIVE: This study aimed to explore the relationship between genetically predicted sleep traits and vertigo with the Mendelian randomization (MR) method. METHODS: Instrumental variables for sleep traits (snoring, sleep duration, insomnia, daytime sleepiness, daytime napping, and chronotype) were adopted from genomewide association studies (GWAS) data of European ancestry from UK Biobank. The summary-level datasets of vertigo were retrieved from the GWAS of FinnGen. Inversevariance weighted (IVW) method was adopted as the main analysis. RESULTS: IVW analysis revealed a significant association between genetically predicted daytime napping (OR = 1.51, 95% CI =1.08-2.12, P = 0.016) and chronotype (OR = 1.13, 95% CI =1.01-1.26, P = 0.033), both of which were associated with an increased risk of vertigo. However, we did not find evidence for a causal effect of snoring, overall sleep duration, long sleep duration, short sleep duration, insomnia, and excessive daytime sleepiness on vertigo. No reverse causality was detected. CONCLUSION: Our findings suggest that abnormal sleep patterns may serve as risk factors for vertigo disorders and offer opportunities for the prevention and management of vertigo disorders.

Humans↗
PubMed2026

Shared Genetic Basis, Biological Function and Causal Relationship Between Sleep Traits and Hypothyroidism: Evidence from a Comprehensive Genetic Analysis.

BACKGROUND: This research attempts to clarify whether there are any genetic similarities between sleep traits and hypothyroidism based on publicly accessible large-scale genomewide association studies. METHODS: The methodology included colocalization analysis, cross-phenotype association analysis, and linkage disequilibrium score regression analysis to find common genetic overlap. Through tissue function specificity and functional mapping, we were able to identify the shared genetic level. Genetic instrumental factors were used for causal inference in two-sample univariate and multivariable Mendelian randomization analyses. RESULTS: A hereditary correlation between hypothyroidism and napping during the day and getting up in the morning (rg= -0.0982, P= 0.0007; rg= -0.101, P= 0.0001). MAGI3, and HLA-DRB1 BX296568.1 may be potential targets for shared treatments. Colocalization and tissue-specific analysis demonstrated that the common genes and SNPs were identified in the thyroid, lung, brain, and lymphatic tissues. Functional analysis emphasized the importance of these common genes in processes like as protein transport, inflammatory response, and MHC class II protein synthesis. Furthermore, an association has been established between hypothyroidism and sleep duration (IVW, OR 1.5208; 95% CI 1.1142-2.0758, P=0.0082) and getting up in the morning (IVW, OR 1.8375; 95%CI: 1.4502-2.3284, P=4.73E-07). Furthermore, the reverse MR analysis revealed no causal connection between aberrant sleep traits and hypothyroidism. The enduring impact of insomnia on hypothyroidism persists despite controlling for alcohol consumption and smoking habits. CONCLUSION: Certain genetic correlations between sleep traits and hypothyroidism have been emphasized. These findings may elucidate the origin of comorbidity and have implications for future clinical trials.

Humans↗
PubMed2026

Causal Effects of Gut Microbiota on Morning Chronotype, Insomnia and Sleep Duration: A Two-Sample Mendelian Randomization Study.

BACKGROUND: The gut microbiota has been shown to be closely associated with brain function; however, whether it exerts a causal influence on sleep traits remains to be further explored. Mendelian randomization (MR) is an emerging epidemiological approach that uses whole-genome sequencing data to infer causal relationships. In this study, we conducted a two-sample MR analysis to investigate the causal effects of gut microbiota on three domains of sleep traits: morning chronotype, insomnia, and sleep duration. METHODS: Single nucleotide polymorphisms strongly associated with 196 gut microbiota taxa were selected as instrumental variables. Morning chronotype, insomnia, and sleep duration were used as outcomes. MR and sensitivity analyses were performed to assess the causal relationships between gut microbiota and sleep traits. RESULTS: Three taxa (Bifidobacteriales, Bifidobacteriaceae, and Bifidobacterium) were negatively associated with morning chronotype, while Tyzzerella 3 showed a positive causal effect on morning chronotype. Oscillibacter was negatively associated with insomnia, whereas four taxa (Negativicutes, Selenomonadales, the Clostridium innocuum group, and Lachnoclostridium) were identified as risk-increasing factors for insomnia. Lentisphaerae and Victivallaceae were positively associated with sleep duration. Actinobacteria and Alistipes had negative effects on long sleep duration, whereas Ruminiclostridium 6 was positively associated with long sleep duration. Four taxa (Victivallales, Anaerofilum, Lentisphaerae, and Lentisphaeria) were negatively associated with short sleep duration. CONCLUSIONS: Our findings suggest that specific gut microbiota taxa may be positively or negatively associated with sleep traits. These results offer new insights into the potential role of gut microbiota in sleep regulation and provide a basis for future studies aimed at understanding whether modulating microbial composition could influence sleep health.

Mendelian randomization↗
PubMed2026

Causal Relationships Between Modifiable Risk Factors and Gastroesophageal Reflux Disease: A Two-Sample Mendelian Randomization Study.

INTRODUCTION: Gastroesophageal reflux disease (GERD) is a prevalent digestive disorder, yet the causal roles of modifiable risk factors remain unclear. This study aims to investigate the causal relationships between 28 modifiable risk factors (including obesity traits, mental health disorders, sleep traits, metabolic comorbidities, and serum parameters) and GERD using two-sample Mendelian randomization (MR). Gastroesophageal reflux disease (GERD). Our findings aim to inform targeted prevention and treatment strategies for GERD. METHODS: This study obtained data from extensive genome-wide association studies (GWAS). Pooled data associated with gastroesophageal reflux associations were obtained from the 23andMe Research team's research, which included a total of 129,080 cases of gastroesophageal reflux and 473,524 controls of European ancestry. We conducted a univariable Mendelian randomization (MR) analysis to ascertain whether genetic evidence of exposure demonstrated a statistically significant association with the risk of GERD. Subsequently, a multivariable MR analysis was carried out to estimate the independent effects of the exposures on GERD. RESULTS: Univariable MR analysis utilizing extensive GWAS data suggested that genetic factors such as BMI, Waist circumference, Arm fat mass (left and right), Leg fat mass (left and right), Attention Deficit and Hyperactivity Disorder (ADHD), Major Depressive Disorder (MDD), Schizophrenia, Negative emotions (including nervousness, anxiety, tension, or depression), Insomnia, Sleep apnea syndrome, Sleep duration, and Snoring, as well as Total cholesterol levels and Apolipoprotein B levels, are associated with the development of GERD. Multivariate Mendelian randomization of BMI and Negative emotion as correction factors showed that Waist circumference, Arm fat mass (left and right), Leg fat mass (left and right), ADHD, Insomnia, Sleep apnea syndrome, and Snoring were associated with an increased risk of GERD (p< 0.05). Conversely, longer sleep duration was associated with a reduced risk of GERD (p< 0.05). DISCUSSION: This MR study reveals novel causal mechanisms in GERD pathogenesis: (1) Peripheral adiposity (arm/leg fat mass) exerts independent effects beyond central obesity, indicating site-specific fat distribution significance; (2) ADHD emerges as a distinct psychiatric risk factor independent of mental disorders; (3) Sleep apnea operates through BMI-independent pathways. Collectively, these findings redefine GERD pathophysiology, highlighting fat depot specificity and brain-gut interactions as critical mechanistic drivers. CONCLUSION: Overall, our findings suggest that multiple risk factors are associated with the risk of GERD. These results provide a theoretical basis for controlling body weight and plasticity, improving sleep habits, and preventing and timely seeking medical attention to reduce the occurrence of psychiatric disorders, which will be important strategies to prevent and alleviate GERD.

Humans↗
PubMed2025

The Interplay Between Sleep and Mental Health: A Genetic Perspective.

Although many facets of sleep, including subjective, behavioral, and neurophysiological features, are closely linked with psychiatric disorders, the natures of these relationships are generally unclear. A given alteration in sleep could reflect a cause (that may mediate genetic risk), consequence, symptom, trigger, epiphenomenon due to shared determinants, or some combination of these. In principle, genetic approaches can be informative: 1) by identifying specific genetic influences on disease mediated by or shared with sleep, which could help the search for biological mechanisms and therapeutic targets, and 2) by providing evidence for causality, which could suggest interventions for modifiable sleep traits. Here, we summarize recent human quantitative and molecular genetic studies on sleep and psychiatric disease, including twin and genome-wide association studies. Despite evidence for shared heritability across many domains, notably depression and insomnia, the field is in its early stages and faces significant challenges including the following: 1) putative causal effects are small, phenotypically nonspecific, not resolved to specific gene pathways, and often bidirectional; 2) most current discovery cohorts are demographically biased and do not capture profound age-related changes in sleep and its genetic architecture; 3) group-level analyses ignore patient-to-patient heterogeneity, including the presence or absence of specific sleep alterations; and 4) a paucity of objective, brain-based data in genetically informative samples hampers making connections with sleep neurophysiology. Nonetheless, as ever-growing genetic tools and resources still hold great potential for translational bridges between basic model systems, human epidemiology, and personalized clinical care, genetic approaches will still likely be needed to reveal sleep's roles in maintaining mental health.

Humans↗
PubMed2026

Rare Coding Variants Reveal Distinct Genetic Architectures Across Multidimensional Sleep Phenotypes.

Sleep and circadian traits have been widely studied using common variants, but the contribution of rare coding variation remains unclear. We analyzed rare coding variants in 397,065 whole-exome sequenced UK Biobank participants across 36 sleep phenotypes from self-report, diagnoses, sleep medication use and accelerometry, and meta-analyzed results with 171,536 whole-genome sequenced All of Us participants of diverse ancestries, with replication in the Mass General Brigham Biobank (N = 31,275). We identified 260 genes associated with sleep phenotypes, including novel associations with sleep medication use in 29 genes and 24 out of 29 have not previously been reported with any sleep phenotypes. We observed modest but significant rare variant heritability and strong genetic correlations between sleep medication use, insomnia and fatigue. Temporal gene expression trajectory analyses indicate that genes associated with self-reported sleep traits show constant high prenatal expression, whereas genes linked to sleep medication phenotypes exhibit peak expression in the late prenatal period. These findings highlight distinct biological mechanisms captured by different measurement sources of sleep phenotypes and reveal rare-variant-informed targets for therapeutic discovery.

exome sequencing↗
PubMed2026

Variants leading to ELAVL2 haploinsufficiency cause a neurodevelopmental disorder with prominent cognitive, behavioral, and neurological features.

RNA-binding proteins (RBPs) regulate gene expression, and a number of RBPs have been implicated in brain function and behavior. Here, we report 16 individuals with a neurodevelopmental disorder and de novo heterozygous variants in ELAVL2, encoding an RBP not previously linked to Mendelian disease. Thirteen individuals were identified through GeneMatcher. Their ELAVL2 variants include two structural, five nonsense, and six missense variants, supporting haploinsufficiency as the primary disease mechanism. The cohort presented with developmental delay, intellectual disability, autism spectrum disorder, seizures, sleep problems, sensory processing issues, emotional instability, and difficulty with socialization. Three additional variants (two missense and one terminal exon truncation), each previously reported in a different large cohort study, were also included for follow-up investigations. We provide multiple lines of evidence linking variants in ELAVL2 to the observed neurodevelopmental and behavioral phenotypes. First, we show that common genetic variants in ELAVL2 are significantly associated with intelligence, motor development, sleep-related traits, and sociability in the general population. Drosophila loss-of-function models provide further independent evidence for a conserved role in the regulation of seizure-like behavior, sensory processing, and sleep. Molecular studies confirm that some of the missense variants are deleterious, leading to decreased protein levels. Together, our integrative study combining Mendelian genetics, clinical and association studies, and animal and molecular modeling supports variants in ELAVL2 as a cause of a neurodevelopmental disorder, with haploinsufficiency as the disease mechanism, and identifies crucial roles of ELAVL2 in neuronal function, cognition, and behavior.

Humans↗
PubMed1977

Neuroticism and dreaming sleep: a case for interactionism in personality research.

The value of a trait approach to sleep and dreaming characteristics is evaluated by reviewing recent research on differential patterns and interactions manifest by high and low neuroticism subjects. Differential patterning of dream content and REM sleep characteristics under positive and negative presleep conditions suggest a qualitative difference in experience and behavior, and a quantitative difference in "importance" attributable to the dreaming sleep process. It is hypothesized that, under "normal" conditions, low neuroticism individuals make more exclusive use of the dreaming period, while under "artificial" conditions, they demonstrate a greater motivation to compensate for restricted REM by intensification of the REM process (shortened REM onset latencies, greater REM rebound, intensified dream experiences). Finally, it is suggested that theories of dreaming sleep should recognize the importance of traits, as well as situational factors to the psychology of dreaming sleep.

Affect↗
PubMed2025

Familial and sporadic non-rapid eye movement parasomnia in adults: clinical and sleep differences.

STUDY OBJECTIVES: The heritable trait of non-rapid eye movement (NREM) parasomnias is well known, but differences between sporadic and familial phenotypes have not been studied. The aim of our study was to evaluate, in a clinical series of adults with NREM parasomnias, clinical and sleep differences between familial versus sporadic forms, and between childhood versus adolescent versus adult-onset forms. METHODS: We prospectively collected clinical features, family history, questionnaires (Epworth Sleepiness Score and Paris Arousal Disorders Severity Scale (PADSS)), and video-polysomnography measures from patients with NREM parasomnias confirmed by video-polysomnography, admitted over a 12-year period. Familial NREM parasomnia was defined as having at least one relative of the index case with NREM parasomnia. RESULTS: Of the 625 consecutive adults with NREM parasomnias, 50% had a family history of NREM parasomnia (most commonly parents, followed by siblings, then children). Compared to those with sporadic NREM parasomnias, participants with familial NREM parasomnias had an earlier age of onset and greater severity of NREM parasomnias (according to the PADSS). They were more likely to report sleepwalking, sleep terrors, and a combination of parasomniac manifestations (but no more confusional arousals or sleep-related eating disorders), and were less likely to report sexsomnia. In contrast, monthly episode frequency, sleepiness score, sleep structure, and EEG and behavioral markers of NREM parasomnias did not differ between groups. CONCLUSIONS: Familial NREM parasomnias have a typical phenotype with an earlier age of onset and a more severe clinical course. This phenotyping may guide medical care and future genetic studies.

Humans↗
PubMed2025

Gut metagenome and plasma metabolome profiles in older adults suggest pyruvate metabolism as a link between sleep quality and frailty.

Poor sleep quality is associated with increased frailty in older adults, but the role of the gut microbiome in this relationship remains unclear. Here, gut metagenome and plasma metabolome were profiled in 1,225 individuals aged 62-96 years. Poor sleep quality was associated with reduced abundances of potential probiotics such as Faecalibacterium prausnitzii and elevated abundances of pathobionts. A gut microbiome sleep quality index (GMSI) was developed to quantify microbial balance related to better sleep quality; higher GMSI scores were inversely associated with frailty and related clinical traits. Pyruvate metabolism emerged as a key microbial pathway linking sleep quality to frailty, with features such as F. prausnitzii abundance and microbial pyridoxal 5'-phosphate biosynthesis implicated in this connection. These findings deepen our understanding of microbiome-metabolome pathways related to sleep quality and frailty in aging and provide a valuable resource for future longitudinal and interventional studies.

Humans↗
PubMed1976

[Premature and usual periods of "rapid" sleep during attacks of diurnal narcolepsy].

The authors studied some psychophysiological characteristics of precocious and usual periods of rapid sleep in 17 patients with polysymptomatic narcolepsy during 92 attacks of day sleep. Precocious rapid sleep duffers from usual one in an inclusion into the dream content the experimental situations and their emotional saturation. The patients underestimated the duration of sleep and were unsatisfied by its quality. These differences indicate to a functional interconnection of rapid sleep with delta-sleep in the process of brain integration of information and assist to understand the pathogenesis of some traits of narcolepsy.

Humans↗
PubMed2026

Mitochondrial Function-Related Genes in Sleep Disorders: A Multi-Omics Mendelian Randomization Study.

Mitochondrial dysfunction is linked to sleep disorders in previous report, but the potential roles of specific genes remain unclear. This study aimed to dissect different subtype-specific genetic associations and their underlying mechanisms. A multi-omics Summary-data-based Mendelian Randomization (SMR) approach was performed to identify potential causal links between mitochondrial function-related genes and sleep disorders. We integrated GWAS data from FinnGen database (the discovery set), independent GWAS datasets (covering different sleep-disorder subtypes and used for validation), and cis-QTLs (including mQTLs, eQTLs, and pQTLs) to perform systematic exploration. Specially, we performed targeted validation of tissue-specific effects, leveraging gene expression data from disease-relevant brain regions within the GTEx database. Our SMR analysis identified mitochondrial function-related genes potentially modulating sleep disorders across biological layers, initially identifying 102 genes at the methylation level, 48 at the gene expression level, and 6 at the protein abundance level. Integrative analysis subsequently prioritized DCXR and ACADVL and revealed their distinct, subtype-specific associations. DCXR exhibited a protective role in sleep apnea while ACADVL showed a paradoxical risk conferring role in daytime sleepiness. In addition, the analysis identified an epigenetic regulatory mechanism for DCXR in which its expression and protein levels are modulated by DNA methylation. Finally, validation in brain-hypothalamus tissue confirmed DCXR as a significant potential protective factor (OR&#x2009;=&#x2009;0.929, 95% CI: 0.887-0.973, P_HEIDI&#x2009;=&#x2009;0.999, FDR&#x2009;=&#x2009;0.2449). Our findings implicate key mitochondrial genes, particularly DCXR and ACADVL, in the pathophysiology of specific sleep disorder subtypes, highlighting potential avenues for precision medicine. Clinical trial number: Not applicable.

Humans↗
PubMed2025

Genome-wide gene-sleep interaction study identifies novel lipid loci in 732,564 participants.

BACKGROUND AND AIMS: Deviations from the population mean in sleep duration have been associated with increased risk for developing dyslipidemia and atherosclerotic cardiovascular disease, but the mechanism of effect is poorly characterized. We performed large-scale genome-wide gene-sleep interaction analyses of lipid levels to identify genetic variants underpinning the biomolecular pathways of sleep-associated lipid disturbances and to suggest possible druggable targets. METHODS: We collected data from 55 cohorts with a combined sample size of 732,564 participants (87&#xa0;% European ancestry) with data on lipid traits (high-density lipoprotein [HDL-c] and low-density lipoprotein [LDL-c] cholesterol and triglycerides [TG]). Short (STST) and long (LTST) total sleep time were defined by the extreme 20&#xa0;% of the age- and sex-standardized values within each cohort. Based on cohort-level summary statistics data, we performed meta-analyses for one-degree of freedom tests of interaction and two-degree of freedom joint tests of the SNP-main and -interaction effect on lipid levels. RESULTS: The one-degree of freedom variant-sleep interaction test identified 10 novel loci (Pint<5.0e-9), and we additionally identify 7 loci within the two-degree of freedom analyses (Pjoint<5.0e-9 in combination with Pint<6.6e-6). Multiple loci, including those mapped to APSH (target for aspartic and succinic acid) and SLC8A1 showed biological plausibility and druggability potential based on literature. CONCLUSIONS: Collectively, the 17 (9 with short and 8 with long sleep) loci provided evidence into the biomolecular mechanisms underlying sleep-associated lipid changes, including potential involvement of the vitamin D receptor pathway. Collectively, these findings may contribute developing novel interventions for treating dyslipidemia in people with sleep disturbances.

Humans↗
PubMed1976

Behavioral characteristics of children with chronic nonspecific diarrhea.

The authors obtained early case histories of 16 children with chronic nonspecific diarrhea and 16 control subjects and found that the index subjects had a significantly higher frequency of sleep problems, crying and irritability, digestive problems excluding diarrhea, overactivity, resistance to discipline, and family history of gastrointestinal problems. They conclude that these behavioral characteristics represent temperamental traits based on physiological factors, perhaps an imbalance of autonomic nervous system function. They speculate that chronic nonspecific diarrhea may occur in association with certain temperamental traits because both the somatic and psychic components stem from a common disturbance in autonomic nervous system function.

Child Behavior Disorders↗
PubMed2025

Exploring the shared genetic basis of attention-deficit/hyperactivity disorder and obstructive sleep apnea: A multi-omics analysis.

BACKGROUND: Observational studies have suggested an association between attention-deficit/hyperactivity disorder (ADHD) and obstructive sleep apnea (OSA), but these findings are often inconsistent due to potential biases from medication use, and varying diagnostic criteria. Genetic analyses can help mitigate these confounding factors, providing additional evidence. METHODS: This study evaluated the genetic correlations between ADHD and OSA using Genome-wide association study (GWAS) summary data, applying linkage disequilibrium score regression (LDSC) and SUPER GeNetic cOVariance Analyzer (SUPERGNOVA). Cross-trait association and colocalization analysis identify potential pleiotropic loci. Tissue enrichment analysis and gene-level analysis of shared genes between OSA and ADHD was conducted. Additionally, bidirectional Mendelian randomization was used to assess potential causal relationships. RESULTS: We found significant genetic correlations between ADHD and OSA (rg&#xa0;=&#xa0;0.309, p&#xa0;=&#xa0;3.252E-27), and identified 8 novel pleiotropic loci through cross-trait association analysis. Tissue enrichment analysis showed that these shared genes were primarily concentrated in brain tissues, particularly in deep gray matter regions, and were associated with immune and inflammatory pathways. Forward Mendelian Randomization analysis showed that ADHD was significantly associated with the risk of OSA (OR 1.070, 95&#xa0;% CI 1.013-1.130, p&#xa0;=&#xa0;0.016), and reverse analysis showed that OSA was significantly associated with the risk of ADHD (OR 1.240, 95&#xa0;% CI 1.106-1.390, p&#xa0;=&#xa0;2.213E-4). CONCLUSION: The findings of this study show a significant positive genetic correlation between ADHD and OSA and each is a risk factor for the other. Inflammation in specific brain regions may be the underlying mechanism for their comorbidity.

Humans↗
PubMed2025

The inversion In(2L)t impacts complex, environmentally sensitive behaviors in Drosophila melanogaster.

Genetic variation in behavioral traits allows organisms to respond and adapt to environmental challenges. Genetic variation in behavior is often affected by many genes and thus has a complex genetic basis. Inversions, the reorientation of genes along the chromosome, tightly link genetic variants together because they suppress recombination. Therefore, inversions are believed to have a major impact on phenotypic variation because they combine the effects of multiple genes, which can pleiotropically alter multiple aspects of behavior. This study investigates how the inversion In(2L)t, found in Drosophila melanogaster populations around the world, impacts different aspects of behavior in an environment-sensitive manner. We test the activity, foraging, and startle-induced behavior of flies with different In(2L)t genotypes across sex and temperatures. We observe that Drosophila homozygous for In(2L)t sleep less frequently, spend more time away from a food source, and have a longer duration of startle response. Additionally, the impacts of In(2L)t on aspects of behavior can be sex-specific and are largely consistent across temperatures. Taken together, our research demonstrates that inversions can regulate aspects of behavior, and suggests hypotheses explaining the distribution of In(2L)t across space and time.

Behavior↗
PubMed1979

Platelet monoamine oxidase activity correlates with social affiliative and agonistic behaviors in normal rhesus monkeys.

After a 4-mo study period, quantitative measures of stable behavioral traits in individual rhesus monkeys correlated significantly with platelet monoamine oxidase (MAO) activity. In particular, behavioral items reflecting social activity and social contact, both agonistic and affiliative, were inversely correlated with enzyme activity. Time spent alone was positively correlated. Since platelet MAO activity is generally stable and predominantly controlled by genetic factors, it might serve as a "genetic marker" for individual differences in "normal" behaviors possibly related to differences in MAO activity in the brain and other tissues.

Age Factors↗