The neuropeptide Y single-nucleotide polymorphism rs16147:T&gt;C moderates the effect of alcohol dependence on depression in male Chinese Han population

Wei, Xiaojie; Cai, Fangfang; Zhou, Siyao; Zhang, Jinjing; Xu, Kewei; Shen, Guanghui; Sun, Huankun; Yang, Fan; Hong, Liuzhi; Zou, Yang; Chen, Yu‐Hsin; Liu, Yanlong; Chen, Li; Wang, Fan; Wang, Wei

doi:10.3389/fpsyt.2022.1012850

Cited by 4 publications

(4 citation statements)

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“…Consistent with previous studies (35,36), we found that anxiety and depression symptoms during withdrawal in AUD patients are highly correlated with alcohol dependence levels in withdrawal. There is an established relationship between alcohol and anxiety; high anxiety levels in AUD patients manifest during alcohol withdrawal (37-39).…”

Section: Discussionsupporting

confidence: 92%

The oxytocin receptor rs2254298 polymorphism and alcohol withdrawal symptoms: a gene–environment interaction in mood disorders

Shen

Yang

et al. 2023

Front. Psychiatry

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ObjectiveAlcohol use disorder (AUD) is a common mental disorder characterized by repeated withdrawal episodes. Negative emotions during withdrawal are the primary factors affecting successful abstinence. Oxytocin is a critical modulator of emotions. OXTR, the oxytocin receptor, may also be a promising candidate for treating alcohol withdrawal symptoms. Previous studies indicated that people with different genotypes of OXTR rs2254298 were reported to suffer from more significant depressive or heightened anxiety symptoms when experiencing early adversity. The present study aims to explore the modulatory role of the polymorphism OXTR rs2254298 on mood disorders during alcohol withdrawal and to help researchers better understand and develop effective relapse prevention and interventions for alcohol use disorders.MethodsWe recruited 265 adult Chinese Han men with AUD. Anxiety and depressive symptoms were measured using the Self-Rating Anxiety Scale and Self-Rating Depression Scale. Alcohol dependence levels were measured using Michigan Alcoholism Screening Test. Genomic DNA extraction and genotyping from participants’ peripheral blood samples.ResultFirst, a multiple linear regression was used to set the alcohol dependence level, OXTR.rs2254298, interaction terms as the primary predictor variable, and depression or anxiety as an outcome; age and educational years were covariates. There was a significant interaction between OXTR rs2254298 and alcohol dependence level on anxiety (B = 0.23, 95% confidence interval [CI]: 0.01–0.45) but not on depression (B = −0.06, 95% CI: −0.30 – 0.18). The significance region test showed that alcohol-dependent men who are GG homozygous were more likely to experience anxiety symptoms than subjects with the A allele (A allele: β = 0.27, p < 0.001; GG homozygote: β = 0.50, p < 0.001). Finally, re-parameterized regression analysis demonstrated that this gene–environment interaction of OXTR rs2254298 and alcohol dependence on anxiety fits the weak differential susceptibility model (R2 = 0.17, F (5,259) = 13.46, p < 0.001).ConclusionThis study reveals a gene–environment interactive effect between OXTR rs2254298 and alcohol withdrawal on anxiety but not depression. From the perspective of gene–environment interactions, this interaction fits the differential susceptibility model; OXTR rs2254298 GG homozygote carriers are susceptible to the environment and are likely to experience anxiety symptoms of alcohol withdrawal.

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Section: Discussionsupporting

confidence: 92%

The oxytocin receptor rs2254298 polymorphism and alcohol withdrawal symptoms: a gene–environment interaction in mood disorders

Shen

Yang

et al. 2023

Front. Psychiatry

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“…As indicated by the risk factor analyses, drinking behaviors may play a role in the susceptibility of female reproductive disorders linked to depression or dysthymia. Research has demonstrated a positive association between alcohol dependence and depression, indicating the potential involvement of interconnected neurobiological mechanisms 56 , 57 . It is widely recognized that alcohol negatively affects female reproduction 38 .…”

Section: Discussionmentioning

confidence: 99%

Epidemiologic and genetic associations of female reproductive disorders with depression or dysthymia: a Mendelian randomization study

Ling,

Dai,

Weng

et al. 2024

Sci Rep

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Observational studies have previously reported an association between depression and certain female reproductive disorders. However, the causal relationships between depression and different types of female reproductive disorders remain unclear in terms of direction and magnitude. We conducted a comprehensive investigation using a two-sample bi-directional Mendelian randomization analysis, incorporating publicly available GWAS summary statistics. Our aim was to establish a causal relationship between genetically predicted depression and the risk of various female reproductive pathological conditions, such as ovarian dysfunction, polycystic ovary syndrome(PCOS), ovarian cysts, abnormal uterine and vaginal bleeding(AUB), endometriosis, leiomyoma of the uterus, female infertility, spontaneous abortion, eclampsia, pregnancy hypertension, gestational diabetes, excessive vomiting in pregnancy, cervical cancer, and uterine/endometrial cancer. We analyzed a substantial sample size, ranging from 111,831 to 210,870 individuals, and employed robust statistical methods, including inverse variance weighted, MR-Egger, weighted median, and MR-PRESSO, to estimate causal effects. Sensitivity analyses, such as Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plots, were also conducted to ensure the validity of our results. Furthermore, risk factor analyses were performed to investigate potential mediators associated with these observed relationships. Our results demonstrated that genetic predisposition to depression or dysthymia was associated with an increased risk of developing PCOS (OR = 1.43, 95% CI 1.28–1.59; P = 6.66 × 10–11), ovarian cysts (OR = 1.36, 95% CI 1.20–1.55; P = 1.57 × 10–6), AUB (OR = 1.41, 95% CI 1.20–1.66; P = 3.01 × 10–5), and endometriosis (OR = 1.43, 95% CI 1.27–1.70; P = 2.21 × 10–7) after Bonferroni correction, but no evidence for reverse causality. Our study did not find any evidence supporting a causal or reverse causal relationship between depression/dysthymia and other types of female reproductive disorders. In summary, our study provides evidence for a causal relationship between genetically predicted depression and specific types of female reproductive disorders. Our findings emphasize the importance of depression management in the prevention and treatment of female reproductive disorders, notably including PCOS, ovarian cysts, AUB, and endometriosis.

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“…The sample size was calculated with G Power (3.1.9.2), according to the previous Gene × Environment studies where the differences of slope between different gene subgroups ranged from approximately 0.05–0.20. 23 , 24 Therefore, to conduct a linear regression with Δslope of 0.05, α value of 0.05 (two‐tailed), power of 0.95, the estimated sample size was 210 participants; that is, the sample size required for the study was 210 participants.…”

Section: Methodsmentioning

confidence: 99%

“…The sample size was calculated with G Power (3.1.9.2), according to the previous Gene × Environment studies where the differences of slope between different gene subgroups ranged from approximately 0.05-0.20. 23,24 Therefore, to conduct a linear regression rs1477341 exhibited more depression symptoms. However, RETN rs3745368 had no significant interaction with alcohol dependence.…”

Section: Participantsmentioning

confidence: 99%

RETN gene polymorphisms interact with alcohol dependence in association with depression

Zhou

et al. 2023

Clinical Laboratory Analysis

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BackgroundPrevious studies suggest that alcohol dependence is associated with increased risk of depression. The occurrence of depressive symptoms is related to polymorphisms in various genetic regions. This study aimed to investigate the interaction of RETN gene polymorphisms (rs1477341, rs3745368) with alcohol dependence on depressive symptoms in adult male during acute alcohol withdrawal.MethodsA total of 429 male adults were recruited in this study. Alcohol dependence was assessed using the Michigan alcoholism screening test (MAST). Depression was assessed using the 20‐item self‐rating depression scale (SDS). Hierarchical regression analysis was used to evaluate the interaction between genes and alcohol dependence on depression. Region of significance (ROS) test was used to explain the interaction effect. The strong and weak forms of the differential susceptibility and diathesis models were used to determine which fits the data better.ResultsOur results showed that MAST scores were significantly positively associated with SDS scores (r = 0.23, p < 0.01) in alcohol‐dependent patients during alcohol withdrawal. The interaction between genotype and alcohol dependence was significant (β = −0.14, p < 0.05) in a strong diathesis‐stress model. Susceptibility for depression symptoms was associated with alcohol dependence in RETN rs1477341 A carriers. Specifically, those that showed more alcohol dependence and the A allele of RETN rs1477341 exhibited more depression symptoms. However, RETN rs3745368 had no significant interaction with alcohol dependence.ConclusionsThe A allele of RETN rs1477341 may correlate with susceptibility to depression symptoms in alcohol‐dependent individuals during acute alcohol withdrawal.

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The neuropeptide Y single-nucleotide polymorphism rs16147:T>C moderates the effect of alcohol dependence on depression in male Chinese Han population

Cited by 4 publications

References 36 publications

The oxytocin receptor rs2254298 polymorphism and alcohol withdrawal symptoms: a gene–environment interaction in mood disorders

The oxytocin receptor rs2254298 polymorphism and alcohol withdrawal symptoms: a gene–environment interaction in mood disorders

Epidemiologic and genetic associations of female reproductive disorders with depression or dysthymia: a Mendelian randomization study

RETN gene polymorphisms interact with alcohol dependence in association with depression

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