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Immune dysregulation has been observed in individuals with sleep disturbance, with HLA molecules play a crucial role in the immune response. This study aimed to investigate the associations between HLA alleles and sleep behaviours, considering several environmental factors. Data were sourced from the UK Biobank. Logistic regression analyses were performed to explore the associations between 359 HLA alleles and 4 sleep behaviours, including chronotype (n = 204,636), insomnia (n = 227,553), snoring (n = 214,350) and daytime dozing (n = 227,197). Furthermore, gene‐environmental interaction studies (GEIS) were conducted to evaluate the interactions of HLA alleles with environmental factors on sleep behaviours. This study analysed a total sample and subgroups stratified by sex to elucidate the impact of HLA alleles on sleep behaviours. Our findings revealed several associations between specific HLA alleles and sleep behaviours. Notably, HLA‐A*23:01 was associated with evening chronotype in the total sample (OR = 0.918, 95%CI: 0.872–0.965), while HLA‐A*32:01 was associated with evening chronotype in males (OR = 1.089, 95%CI: 1.037–1.144). Furthermore, GEIS identified multiple sets of interactions associated with sleep behaviours. For example, the interaction of HLA‐DPA1*01:04 with alcohol consumption was associated with daytime dozing in the total sample (OR = 1.993, 95%CI: 1.351–2.941), while the interaction of HLA‐DQB1*05:04 with ever suffered mental distress preventing usual activities was associated with insomnia in males (OR = 0.409, 95%CI: 0.254–0.658). Our findings highlight the involvement of HLA in sleep regulation and underscore the potential interactions between HLA alleles and environmental factors in modulating susceptibility to sleep behaviours. [ABSTRACT FROM AUTHOR]

Background Depression has been linked to an increased risk of cardiovascular and respiratory diseases; however, its impact on cardiac and lung function remains unclear, especially when accounting for potential gene–environment interactions. Methods We developed a novel polygenic and gene–environment interaction risk score (PGIRS) integrating the major genetic effect and gene–environment interaction effect of depression-associated loci. The single nucleotide polymorphisms (SNPs) demonstrating major genetic effect or environmental interaction effect were obtained from genome-wide SNP association and SNP-environment interaction analyses of depression. We then calculated the depression PGIRS for non-depressed individuals, using smoking and alcohol consumption as environmental factors. Using linear regression analysis, we assessed the associations of PGIRS and conventional polygenic risk score (PRS) with lung function (N  = 42 886) and cardiac function (N  = 1791) in the subjects with or without exposing to smoking and alcohol drinking. Results We detected significant associations of depression PGIRS with cardiac and lung function, contrary to conventional depression PRS. Among smokers, forced vital capacity exhibited a negative association with PGIRS (β  = −0.037, FDR = 1.00 × 10−8), contrasting with no significant association with PRS (β  = −0.002, FDR = 0.943). In drinkers, we observed a positive association between cardiac index with PGIRS (β  = 0.088, FDR = 0.010), whereas no such association was found with PRS (β  = 0.040, FDR = 0.265). Notably, in individuals who both smoked and drank, forced expiratory volume in 1-second demonstrated a negative association with PGIRS (β  = −0.042, FDR = 6.30 × 10−9), but not with PRS (β  = −0.003, FDR = 0.857). Conclusions Our findings underscore the profound impact of depression on cardiac and lung function, highlighting the enhanced efficacy of considering gene–environment interactions in PRS-based studies. [ABSTRACT FROM AUTHOR]

Smoking and alcohol consumption were associated with the development of depression and anxiety. 3′UTR APA quantitative trait loci (3'aQTLs) have been associated with multiple health states and conditions. Our aim is to evaluate the interactive effects of 3'aQTLs-alcohol consumption/tobacco smoking on the risk of anxiety and depression. The 3'aQTL data of 13 brain regions were extracted from the large-scale 3'aQTL atlas. The phenotype data (frequency of cigarette smoking and alcohol drinking, anxiety score, self-reported anxiety, depression score and self-reported depression) of 90,399–103,011 adults aged 40–69 years living in the UK and contributing to the UK Biobank during 2006–2010, were obtained from the UK Biobank cohort. The frequency of cigarette smoking and alcohol drinking of each subject were defined by the amount of smoking and alcohol drinking of self-reported, respectively. The continuous alcohol consumption/smoking terms were further categorized in tertiles. 3'aQTL-by-environmental interaction analysis was then performed to evaluate the associations of gene-smoking/alcohol consumption interactions with anxiety and depression using generalized linear model (GLM) of PLINK 2.0 with an additive mode of inheritance. Furthermore, GLM was also used to explore the relationship between alcohol consumption/smoking with hazard of anxiety/depression stratified by allele for the significant genotyped SNPs that modified the alcohol consumption/smoking-anxiety/depression association. The interaction analysis identified several candidate 3'aQTLs-alcohol consumption interactions, such as rs7602638 located in PPP3R1 (β = 0.08, P = 6.50 × 10−6) for anxiety score; rs10925518 located in RYR2 (OR = 0.95, P = 3.06 × 10−5) for self-reported depression. Interestingly, we also observed that the interactions between TMOD1 (β = 0.18, P = 3.30 × 10−8 for anxiety score; β = 0.17, P = 1.42 × 10−6 for depression score), ZNF407 (β = 0.17, P = 2.11 × 10−6 for anxiety score; β = 0.15, P = 4.26 × 10−5 for depression score) and alcohol consumption was not only associated with anxiety, but related to depression. Besides, we found that relationship between alcohol consumption and hazard of anxiety/depression was significantly different for different SNPs genotypes, such as rs34505550 in TMOD1 (AA: OR = 1.03, P = 1.79 × 10−6; AG: OR = 1.00, P = 0.94; GG: OR = 1.00, P = 0.21) for self-reported anxiety. The identified 3'aQTLs-alcohol consumption/smoking interactions were associated with depression and anxiety, and its potential biological mechanisms need to be further revealed. Our study identified important interactions between candidate 3'aQTL and alcohol consumption/smoking on depression and anxiety, and found that the 3'aQTL may modify the associations between consumption/smoking with depression and anxiety. These findings may help to further explore the pathogenesis of depression and anxiety. • Interaction between rs7602638 located in PPP3R1 and alcohol consumption was positively associated with anxiety score. • Interaction between rs10925518 in RYR2 and alcohol consumption was negatively correlated with self-reported depression. • Interactions between TMOD1, NLRP1, ZNF407 and alcohol consumption were positively associated with anxiety and depression. [ABSTRACT FROM AUTHOR]

Previous studies have observed the protective effects of alcohol and the deleterious effects of smoking on chronic pain in the general population. Interestingly, alcohol and smoking were negatively associated with the severity and status of depression and anxiety. Meanwhile, depression and anxiety are associated with an increased perception of pain severity. However, little is known regarding the associations of alcohol and smoking with chronic pain in people with depression and anxiety. Depression was assessed with the Patient Health Questionnaire-9 (PHQ-9). Anxiety was measured with items based on the Generalized Anxiety Disorder-7 (GAD-7). We used logistic and liner regression models to examine associations between smoking, alcohol consumption, and 8 pain phenotypes, including (1) headache; (2) facial pain; (3) neck or shoulder pain; (4) back pain; (5) stomach or abdominal pain; (6) hip pain; (7) knee pain; and (8) multisite chronic pain. Additionally, we did subgroup analysis in the non-depression and anxiety groups and comorbid anxiety-depression group to test if there were differences. Our results found that alcohol consumption was negatively associated with headache in depression group (odds ratio (OR) = 0.71, P = 0.007), which was also found in anxiety group (OR = 0.63, P = 0.002), comorbid anxiety and depression group (OR = 0.68, P = 0.025), and non-depression and anxiety group (OR = 0.72, P = 0.002). We observed that smoking was positively associated with back pain in depression group (OR = 1.14, P = 0.016) and mild to moderate depression group (OR = 1.13, P = 0.049). Also, positive associations of smoking with hip pain were found in the anxiety group (OR = 1.37, P = 0.001) and comorbid anxiety and depression group (OR = 1.31, P = 0.022). Our research indicated that for participants with depression and anxiety, alcohol consumption was negatively associated with most of the pain phenotypes, while smoking was positively associated with most of the 8 pain phenotypes. [ABSTRACT FROM AUTHOR]