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Analysis of data from the NHANES 1999–2018 and Mendelian randomization studies reveals the relationship between alcohol use and rheumatoid arthritis

Nutrition Journal volume 23, Article number: 156 (2024) Cite this article

Abstract

Background

Rheumatoid arthritis (RA) is a complex multifactorial autoimmune disease affected by genetics and environmental factors. The relationship between alcohol consumption and RA remains controversial. This study aimed to assess the association between alcohol consumption and RA risk using cross-sectional analysis and Mendelian randomization (MR).

Methods

We investigated the association between alcohol consumption and RA risk through multivariate linear regression and subgroup analyses. Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 1999–2018 which involved 32,308 participants. Subsequently, a two-sample MR study was conducted to assess the causal effect of spirits intake on RA. Instrumental variables (IVs) for spirits intake were screened from genome-wide association study (GWAS) datasets, including 69,949 individuals from the UK Biobank study, while summary statistics relating to RA were obtained from a GWAS meta-analysis of 417,256 participants. The primary inverse variance weighted (IVW) method and other supplementary MR methods were used to estimate the causal association between spirits intake and RA. Sensitivity analyses were performed to confirm the robustness and reliability of the results.

Results

In the cross-sectional analysis, we observed that alcohol consumption was significantly positively linked with RA risk (odds ratio [OR] = 1.030; 95% confidence interval [CI], 1.025–1.034). According to subgroup analyses stratified by age, sex, race, smoking status, marital status, education attainment, and body mass index (BMI), consistently showed a positive relationship between alcohol consumption and RA risk in each subgroup (all OR > 1, P < 0.05). Furthermore, MR analysis indicated a causal association between spirits intake and RA (OR = 1.043, P < 0.05). Sensitivity analyses supported the robustness and reliability of these findings (all P > 0.05).

Conclusion

This study indicated that alcohol consumption is correlated with an increased risk of RA, but further studies are necessary to clarify the exact association.

Peer Review reports

Introduction

An estimated 0.69% of people worldwide have rheumatoid arthritis (RA), a chronic systemic, autoimmune condition with a 4.8 million disability-adjusted life years (DALYs) global burden [1, 2]. As a leading cause of disability, RA is associated with reduced life expectancy, secondary health complications, and socioeconomic damage [3]. Evidence suggests that hereditary factors account for approximately 60% of RA risk, and a considerable proportion of the risk may also be attributable to environmental and lifestyle factors [4]. Currently, smoking is the most well-established environmental risk factor for the development of seropositive individuals with RA [5]. Additional environmental risk factors for RA, such as dietary variables, vitamin D levels, and level of education, have been investigated [6,7,8]. However, the results were not definitive.

Since ancient times, numerous societies used alcohol (C2H5OH), usually known as ethanol, as one of the most widely consumed psychoactive substances globally [9]. Alcohol dehydrogenase (ADH) first breaks down ingested alcohol to the extremely poisonous acetaldehyde, which is then rapidly converted by aldehyde dehydrogenase (ALDH) into harmless acetate [10]. The fast metabolism of acetaldehyde causes individuals with alcoholism to have higher serum acetate levels [11]. Consequently, interest in important metabolic intermediates such as acetate has significantly increased due to their possible effects on human health. A number of studies have shown that alcohol consumption may affect the innate and adaptive immune systems [12]. Therefore, alcohol intake has recently attracted attention as a potential risk factor for autoimmune disorder such as RA.

Nevertheless, research findings on the impact of alcohol consumption on the course of RA disease have been inconclusive. There is a well-accepted assumption that a negative relationship exists between alcohol use and the occurrence of RA. Multiple meta-analyses and clinical investigations have supported this hypothesis [13,14,15].

Some studies focusing on women have expressed differing opinions [16, 17]. Other studies have indicated that alcohol consumption dose not significantly influence disease activity in individuals with RA [18, 19]. Previous studies examining the correlation between alcohol intake and the likelihood of developing RA may have been affected by limitations in sample size and the potential for reverse causation bias.

The National Center for Health Statistics (NCHS), responsible for compiling data on the health and nutritional status of the civilian noninstitutionalized US population, is conducting an ongoing cross-sectional study called the National Health and Nutrition Examination Survey (NHANES) [20]. Consequently, NHANES may provide a substantial sample of nationally representative data significantly enhancing the validity and reliability of the findings.

Employing variations associated with potential risk factors of interest as instrumental variables (IVs), Mendelian randomization (MR) analyses are increasing in popularity as a means of determining the causal significance of risk factors for disease [21]. Furthermore, because germline genetic variants are assigned at random during meiosis and are unaffected by environmental variables, this method is less susceptible to reverse causation and confounding [22].

In the present study, a cross-sectional analysis was performed using the NHANES data to determine the correlation between alcohol intake and the likelihood of developing RA. Subsequently, this study employed a two-sample MR analysis to assess further the causal association between spirits intake and the risk of RA.

Study methodology

Cross-sectional study

Study population

The NHANES database (https://www.cdc.gov/nchs/nhanes/index.htm) contains the data used to conduct the current analysis. To improve the statistical power, data from 1999 to 2018 were combined to increase the sample size for this project. The NHANES protocols were authorized by the NCHS Research Ethics Review Board and each participant in the NHANES study provided signed informed consent form upon enrollment. Data pertaining to demographics, physical examination, and questionnaires were collected for this research. This study included individuals over 20 years old with complete data on alcohol consumption and RA who were registered in the NHANES Mobile Examination Center between 1999 and 2018. After excluding participants with incomplete questionnaire data or missing information on RA status during follow-up, a total of 32,308 individuals were selected for analysis (Fig. 1).

Fig. 1
figure 1

Study flowchart. NHANES, National Health and Nutrition Examination Survey; RA, rheumatoid arthritis

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Definition of exposure and outcomes

The results of the questionnaire were used to determine whether the participant has a history of RA. Participants were questioned over two inquiries pertaining to RA. (1) Have you ever received a diagnosis of arthritis from a doctor or other healthcare professional? (2) What specific type of arthritis was it? If the initial response was affirmative and the subsequent question was responded with “rheumatoid arthritis”, the participants were classified as having RA.

The primary exposure variable was alcohol consumption (g/day), assessed by determining usual alcohol intake with the National Cancer Institute (NCI) method. This estimated long-term intake employs data from 2 days of 24 h recalls [23]. The type of alcohol consumed was not specified.

Other covariates

To enhance the precision and reliability of the present findings, potential confounding factors were considered as covariates based on previous research on RA [24, 25]. These factors include sex (male, female), age (20–60 years, ≥ 60 years), ethnicity (non-Hispanic Black, non-Hispanic White, other Hispanic, Mexican American, other races), smoking status (current smoker, former smoker, never smoker), marital status (widowed/divorced/separated, married/cohabiting, never married), citizenship status (not a citizen or citizen), body mass index (BMI, obese: ≥30 kg/m2, overweight: 25 to < 30 kg/m2, underweight: <18.5 kg/m2, normal: 18.5 to < 25 kg/m2), education level (high school grad/GED, 9-11th grade, less than 9th grade, some college or AA degree, college graduate or above), and the ratio of family income to poverty.

Statistical analysis

The statistical analyses were conducted using the Statistical Package for the Social Science (SPSS Statistics 26) and R software (The R Foundation; http://www.r-project.org; version 4.1.3). This study employed the NHANES-recommended sampling weights, determined based on a stratified multistage probabilistic sampling design. The P values for continuous variables in the population baseline table were examined using a weighted t-test. In contrast, the P values for categorized variables were determined using a weighted chi-square test. A multivariate linear regression model was used to examine the relationship between alcohol use and RA risk after controlling for confounders: Model 1, with no changed elements. Model 2 was adjusted for age, sex, and race. Model 3 included additional adjustments for education level, smoking status, marital status, and BMI. Additionally, subgroup analyses were performed using these factors as stratification variables. P values less than 0.05 on two-sided were regarded as statistically significant.

Mendelian randomization study

Data sources and study population

The IEU OpenGWAS project (https://gwas.mrcieu.ac.uk/) was used to download pertinent genome-wide association study (GWAS) datasets. This study used summary statistics from a GWAS meta-analysis of the European Bioinformatics Institute (EBI) database. The dataset, ebi-a-GCST90018910, had a substantial sample size of 417,256 individuals [26]. Summary statistics for spirits intake were sourced from a GWAS conducted by the Neale laboratory using data from the UK Biobank with a sample size of 69,949 individuals (ukb-b-3751). Patients diagnosed with RA were identified using the code M06.991 in the International Classification of Diseases (ICD), Tenth Revision. All individuals in these databases were of European descent. Each original study obtained informed consent from participants and ethics approval.

Screening of instrumental variables

First, as instrumental variables (IVs), single-nucleotide polymorphisms (SNPs) linked to exposure factors (P < 5 × 10− 8) were selected. Second, all independent IVs were found to be devoid of linkage disequilibrium (LD) for the examined SNPs (r2 = 0.001, kb = 10,000) [27]. Third, to assess weak IV bias, the F statistic for each SNP was determined, and those with an F value less than 10 were eliminated. Fourth, the palindromic SNPs were eliminated with intermediate allele frequencies and harmonized the corresponding exposure and outcome datasets using effect allele frequencies. Finally, the database of human genotype-phenotype relationships, PhenoScanner (version 2.0) [28], was used to identify and eliminate SNPs associated with confounding factors.

Statistical analysis

Multiple analytical approaches were employed in the present study. The primary method used to assess the causal relationship between genetically predicted spirits intake and RA risk was the inverse-variance weighted (IVW) approach. For this investigation, four MR analysis approaches, namely, MR-Egger, weighted median, simple mode, and weighted mode were selected for complementary analyses. Although the IVW method offers precise estimates, it may be biased by invalid IVs and pleiotropic effects. Therefore, we conducted three sensitivity analyses to obtain an unbiased estimate and account for possible pleiotropy. Cochrane’s Q test was employed to evaluate the possibility of heterogeneity, with a significance level of P < 0.05 indicating the existence of heterogeneity. The horizontal pleiotropy was evaluated using the MR-Egger intercept test, where pleiotropy was suggested by P < 0.05. Additionally, a leave-one-out sensitivity analysis was performed to assess the reliability of the MR findings. All the statistical analyses were conducted in R software (version 4.1.3), using the R package TwoSampleMR (version 0.5.6).

Results

NHANES study

Population characteristics of the study subjects

In the current study, 32,308 individuals aged 20 to 60 were included (30,086 with RA and 2,222 without RA, Table 1). Compared to healthy individuals, patients with a history of RA were more likely to be older, predominantly female, and of non-Hispanic Black origin (P < 0.05). Additionally, they had lower educational attainment, a lower poverty-to-income ratio, and a higher prevalence of smoking (P < 0.05). Individuals who were widowed, divorced, or separated had a higher incidence of RA compared to those who were married, cohabiting or single and never married (P < 0.05). As expected, RA patients had significantly higher BMI and alcohol intake (P < 0.05).

Table 1 Baseline characteristics of participants with and without RA history
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We arranged the RA patients’ alcohol intake values from smallest to largest and divided them into four equal quartiles. Based on these quartile, the individuals were subsequently separated equally into 4 groups, and their baseline characteristics were compared according to the quartile group (Q1-Q4). As shown in Table 2, significant differences were observed between the highest and lowest quartiles of alcohol intake in terms of sex, race, marital status, education attainment, and BMI distributions (P < 0.05). Patients who consumed more alcohol were predominantly male and had a higher incidence of smoking (P < 0.05). No significant differences were observed between the highest and lowest quartiles in terms of citizenship or poverty-to-income ratio.

Table 2 Baseline characteristics of participants with RA according to alcohol intake quartiles
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Relationship between alcohol intake and RA based on observations

The odds ratios (ORs) for Model 1, Model 2, and Model 3 were 1.027 [95% confidence interval (CI) 1.023–1.031], 1.030 (95% CI 1.026–1.034), and 1.030 (95% CI 1.025–1.034), respectively, indicating a positive correlation between the incidence of RA and alcohol intake (Table 3). Furthermore, alcohol consumption quartiles were compared, using the first quartile used as a reference (Q1). In Model 1, which was unadjusted for covariates, patients with increasing quartiles of alcohol intake (Q2, OR: 0.070, 95% CI: 0.047–0.103; Q3, OR: 1.266, 95% CI: 0.926–1.732; Q4, OR: 3.885, 95% CI: 3.222–4.684) exhibited a higher risk of RA compared to Q1 (all P values for trend < 0.05). This increased risk remained significant in Model 2 (P < 0.05), adjusted for age, sex, and race (Q2, OR: 0.092, 95% CI: 0.063–0.136; Q3, OR: 1.557, 95% CI: 1.121–2.218; Q4, OR: 6.045, 95% CI: 4.884–7.483) and in Model 3, which was further adjusted for education level, smoking status, marital status, and BMI (Q2, OR: 0.091, 95% CI: 0.062–0.134; Q3, OR: 1.909, 95% CI: 1.332–2.736; Q4, OR: 6.930, 95% CI: 5.570–8.623).

Table 3 Associations between alcohol intake and RA risk
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To gain further insight into the relationship between alcohol intake and the risk of RA, we conducted subgroup analyses stratified by age, sex, race, martial status, smoking status, education level, and BMI. In each subgroup, a significant positive correlation was observed between alcohol intake and RA risk, both before and after adjusting for possible variables (all OR > 1, P < 0.05, Table 4).

Table 4 Subgroup analysis for the association between alcohol intake and RA risk
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Mendelian randomization study

Causal relationship between spirits intake and the risk of RA

An MR analysis was conducted to evaluate the possible causal relationship between spirits intake and RA risk, as the multivariate linear regression analysis above indicated a substantial positive correlation between the two variables. In the majority of the studies, we considered 17 IVs (genetic variations) associated with spirits intake. As shown in Fig. 2, the estimated effect of spirits intake on RA by each SNP is displayed in a forest plot. The direction of each SNP’s OR indicates either a protective or risk effect. Five SNPs (rs11612594, rs140255666, rs9826278, rs34300267, and rs79668485) to the left of the invalid line exhibited a protective effect against RA, while 12 SNPs (rs138046610, rs144504331, rs28603365, rs73568958, rs117933182, rs77094623, rs111610561, rs138235027, rs79181129, rs190371197, rs10257147, and rs73340194) to the right of the invalid line were associated with an increased RA risk. According to the IVW findings, there was a significant correlation between genetically predicted spirits intake and an elevated risk of RA (OR = 1.043, P < 0.05, Table 5).

Fig. 2
figure 2

Forest plot of SNPs associated with RA risk. SNPs are ordered by chromosome numbers. The dot and the bar indicate the causal effect of spirits intake level on the risk of RA. Protective SNPs against RA risk are shown on the left of the invalid line; SNPs with predisposition risk to RA are shown on the right of the invalid line. Note A shot of spirits (whisky or Baijiu), about 30 mL, with an alcohol content of 40% [29]

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Table 5 MR estimates for the causal effect alcohol intake on RA risk
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However, MR-Egger (OR = 1.022, P = 0.686), the weighted median (OR = 1.044, P = 0.095), the simple mode (OR = 1.042, P = 0.384), and the weighted mode (OR = 1.055, P = 0.165) did not strongly support a causal association between spirits intake and RA risk (Table 5). The effect estimates of exposure to RA, as determined by several MR techniques, are displayed in Fig. 3. Each point in the scatter plot represents a SNP, and the 95% CI is indicated by the line at each point. The horizontal coordinate shows the impact of SNPs on exposure factors (spirits intake), and the vertical coordinate represents the impact of SNPs on outcomes (RA). The colored lines show the MR fit results. The results show that spirits intake had a suggestive risk effect on RA, with an OR of 1.043 (P < 0.05), meaning that for every unit increase in log-odds of spirits intake, the risk of RA increased by 1.043.

Fig. 3
figure 3

Scatter plot for of the associations between spirits intake and RA risk. Each point in the scatter plot represents an IV (genetic variant). The line on each point reflects the 95% CI, and the horizontal coordinate is the effect of SNPs on spirits intake. The vertical coordinate is the effect of SNPs on RA. SNP effects were plotted as lines for the IVW (red line), MR-Egger (blue line), simple mode (green line), weighted median (purple line), and weighted mode (orange line) methods. The slope of each line represents the causal estimation. A positive slope indicates that spirits intake had a positive effect on RA risk. Note A shot of spirits (whisky or Baijiu), about 30 mL, with an alcohol content of 40% [29]. MR, Mendelian randomization; SNP, single nucleotide polymorphism

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Sensitivity analysis

Several sensitivity analyses, including Cochrane’s Q test, the MR-Egger intercept test, and the leave-one-out analysis for spirits intake with 17 genetic variations, were conducted as assess the stability of the results. Cochrane’s Q test revealed no heterogeneity in the causal effect of spirits intake on RA (all P > 0.05, Table 5). Additionally, no horizontal pleiotropy was detected during spirits exposure according to the MR-Egger intercept test (P = 0.685, Table 5). As shown in Fig. 4A, the funnel plot depicting the causal relationship between spirits intake and RA was nearly symmetrically distributed. The reliability and dependability of the MR results were supported by the leave-one-out graph, which showed that all lines were positioned to the right of the “0 line”, indicating that the exclusion of any single SNPs did not significantly impact the results (Fig. 4B).

Fig. 4
figure 4

Sensitivity analyses for the effect of spirits intake on RA risk. (A) The funnel plot of the causality of spirits intake and RA was almost symmetrically distributed, suggesting that no significant heterogeneity existed. (B) The leave-one-out graph showed that all lines were located to the right of the “0 line”, suggesting that the removal of any SNPs did not fundamentally affect the results, supporting the reliability of the MR results. Note A shot of spirits (whisky or Baijiu), about 30 mL, with an alcohol content of 40% [29]. MR, Mendelian randomization

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Discussion

The current study investigated the association between alcohol intake and RA using a two-sample MR analysis and a cross-sectional analysis based on the NHANES 1999–2018 cohort. The results of this cross-sectional investigation demonstrated a positive correlation between alcohol use and RA risk. Additionally, the causal relationship between spirits intake and RA was supported by a two-sample MR analysis based on GWAS datasets, indicating that spirits intake is a modifiable risk factor for RA.

As noted in the introduction, alcohol consumption is a common social activity across many cultures. It is estimated that 32.5% of the global population consumes alcohol [30]. Unfortunately, a significant portion of the population suffers from alcohol addiction. Alcohol use has been associated with various health issues, including diabetes and obesity [31]. However, there has been a long-standing debate over the role of light-to-moderate alcohol consumption on health outcomes [32]. RA is a complex, multifactorial autoimmune disease. According to several earlier research, moderate alcohol use reduces RA patients’ disease activity in a dose-dependent way [13,14,15]. The possible mechanism may involve immune system responses to alcohol exposure, including effects on proinflammatory cytokines, antigen-specific IgG, IL-21 production by TFH cells, B-cell maturation and proliferation, antigen presentation, and the ability of antigen-presenting cells (APCs) to activate T cells [11]. Additionally, alcohol intake may influence the gut microbiota, affecting autoimmune disease [33]. In recent decades, this inference has been partially supported by the data of other clinical and experimental studies. However, whether these results represent genuine protective effects or mere methodological limitations remains unclear. More importantly, this has substantial consequences for policy and practice.

Elucidating the nature of the relationship between alcohol intake and RA is essential, yet more challenging than expected. Significant progress has been made in both techniques and the number of participants, resulting in a wide range of findings based on observational data. This is due to the growing accessibility of extensive cohort datasets and advanced statistical tools. An observational study involving 16,762 participants demonstrated that alcohol intake dose not have a protective impact on RA when accounting for potential confounding factors [18]. Similarly, a nested case-control research in a Swedish cohort reported consistent results [34]. Additionally, two extensive prospective cohort studies, one with 101,501 Chinese and the other with 238,131 American individuals, found that alcohol use increased RA risk in women [16, 17].

The NHANES database, with its nationally representative data, offers a unique opportunity to derive unbiased estimates and generalize findings to a large population. According to the NHANES data from 1999 to 2018, RA patients tender to consume alcohol at a substantially higher rate. After adjusting for possible confounders, multivariate linear regression analysis indicated a strong positive correlation between alcohol use and RA. Nonetheless, residual confounding factors and reverse causation are unavoidable in observational studies [35]. In the current study, however, the potential confounding variables were adjusted, such as education level, smoking status, BMI, race, age, and sex. A randomized controlled trial (RCT), wherein participants are randomly assigned to different levels of alcohol intake and followed up for health effects, could be used to mitigate confounding issues [36]. However, based on short-term trials, we cannot tell whether the benefits of alcohol would accrue in the long term. The difficulties of carrying out long-term RCTs evaluating alcohol consumption and health outcomes, including the moral dilemmas of prolonged exposure to a known human carcinogen, the likelihood of noncompliance with assigned long-term levels of alcohol intake or nonintake, and the prohibitive expense, have so far been shown to be insurmountable obstacles [37].

Mendelian randomization analyses serve as a valuable complement to RCTs. Increasingly used in epidemiology to assess unbiased causal effects of exposures on specific outcomes by employing genetic factors [38]. Genetic alleles, being dispersed randomly in the population at birth and not influenced by reporting bias, might be used instead of exposure to minimize confounding factors, reverse causality, and measurement error [39]. There is a complicated relationship between alcohol use and the risk of RA. A two-sample MR analysis was carried out to ascertain the causal link between them further, in addition to utilizing nationally representative observational research, since RCTs have been shown to be impractical. Compared to other MR approaches, the IVW method has significantly higher statistical power [40]. As a result, the IVW method was selected as the primary way for screening the MR results. Based on the MR results from the European population, researchers have acquired a greater understanding of the beneficial causal effect of alcohol use on RA. However, some previous MR investigations have not found significant causal associations between alcohol intake and RA [41, 42], which is inconsistent with our results. One probable reason may be a difference in exposure factors. Unlike previous MR studies concentrating only on alcohol intake frequency, our study focused on the amount of alcohol consumed, which better reflects drinking levels. Additionally, alcohol intake is a broad concept that includes the intake of alcohol components in all alcoholic beverages, such as beer, wine, spirits, fruit wine, liqueur and so on. When calculating alcohol intake, the volume of the beverage and the volume fraction of alcohol in it are usually taken into account. Spirits intake has a relatively narrow range, primarily referring to the consumption of spirits, a specific type of alcoholic beverage. Spirits are high-alcohol beverages produced through distillation processes, including whiskey, vodka, brandy, rum, and so on. Bae SC et al. did not distinguish the types of alcoholic beverages, but instead considered “alcohol intake” as the exposure factor [42]. Different types of alcoholic beverages contain not only alcohol, but also other ingredients (such as carbohydrates in beer, polyphenols in wine, ets.) that may either synergize or antagonize the effects of alcohol on diseases. To minimize the influence of non-alcoholic components in alcoholic beverages on our results, we selected “spirits intake” as the exposure factor. Through MR analysis, a significant causal relationship was discovered between the spirits intake and RA. Specifically, a higher spirits intake was found to be significantly and positively correlated with an increased risk of RA. This is consistent with the results derived from the analysis of the NHANES database.

Nonetheless, this study has certain limitations. First, this study used a small number of SNPs as IVs which may have hampered the potential to identify a connection. Second, our sample primarily consisted of individuals of European and American descent, so further research is needed to validate these findings in other populations.

Conclusion

In summary, this comprehensive observational study utilized NHANES and MR analysis, revealing a clear association between alcohol use and the likelihood of developing RA. Nevertheless, given the constraints of the study, further research is needed to clarify the impact of alcohol use on the progression of RA.

Data availability

The study was based on public databases. The datasets can be found on the NHANES website (https://www.cdc.gov/nchs/nhanes/index.htm) and the IEU OpenGWAS project (https://gwas.mrcieu.ac.uk/).

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Acknowledgements

We sincerely thank all staff, participants, and institutions that have contributed to the NHANES database and the publicly available GWAS database.

Funding

This work was supported by Science and Technology Project of Huzhou (Grant No. 2022GY24) and the Medicine and Health Science and Technology Plan Projects of Zhejiang Province (Grant No. 2023RC123).

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Authors and Affiliations

  1. Department of Rheumatology and Immunology, Huzhou Third Municipal Hospital, Affiliated Hospital of Huzhou University, Huzhou, China

    Xiaobing Yang & Xiaoqin Long

  2. Department of Clinical Nutrition, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China

    Pan Xiao

  3. Department of Orthopaedics, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China

    Qinwen Ge

  4. Department of Integrated Chinese and Western Medicine, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China

    Lei Zhang

  5. Department of Plastic Surgery, Zhejiang Hospital, Hangzhou, China

    Xiaowei Wang

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  1. Xiaobing Yang
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  2. Xiaoqin Long
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  3. Pan Xiao
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  4. Qinwen Ge
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  5. Lei Zhang
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  6. Xiaowei Wang
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Contributions

XBY and XXW conceived and designed the study. XQL, PX, and QWG collected data and performed the statistical analysis. LZ drafted the manuscript. All authors contributed, and approved the final version for publication.

Corresponding authors

Correspondence to Lei Zhang or Xiaowei Wang.

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Ethics approval and consent to participate

This study was conducted according to the guidelines laid down in the Declaration of Helsinki, and all procedures involving research study participants were approved by the institutional review board of the National Center for Health Statistics (NCHS). Written informed consent was obtained from all participants.

Competing interests

The authors declare no competing interests.

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Yang, X., Long, X., Xiao, P. et al. Analysis of data from the NHANES 1999–2018 and Mendelian randomization studies reveals the relationship between alcohol use and rheumatoid arthritis. Nutr J 23, 156 (2024). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12937-024-01057-6

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Keywords

Nutrition Journal

ISSN: 1475-2891

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