Alcohol Consumption and Risk of Common Autoimmune Inflammatory Diseases—Evidence From a Large-Scale Genetic Analysis Totaling 1 Million Individuals

Jiang, Xia; Zhu, Zhaozhong; Manouchehrinia, Ali; Olsson, Tomas; Alfredsson, Lars; Kockum, Ingrid

doi:10.3389/fgene.2021.687745

Cited by 17 publications

(15 citation statements)

References 25 publications

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“…Leveraging 2-sample mendelian randomization (MR), several studies reported directional effects for pairs of psychiatric and immune-related phenotypes, including positive effects of schizophrenia on systemic lupus erythematosus and immune-mediated bowel and biliary diseases and positive effects of major depression and alcohol use on asthma . On the other hand, several MR studies found nonsignificant effects pertaining to certain psychiatric-immune comorbidities . Another possibility is that shared liability is influenced by a correlated third variable with associations with one or both phenotypes.…”

Section: Introductionmentioning

confidence: 99%

“…8,9 On the other hand, several MR studies found nonsignificant effects pertaining to certain psychiatric-immune comorbidities. [18][19][20][21] Another possibility is that shared liability is influenced by a correlated third variable with associations with one or both phenotypes. Many risk factors are associated with both psychiatric and immune-related disorders, briefly reviewed within the eMethods of Supplement 1.…”

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confidence: 99%

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An Atlas of Genetic Correlations and Genetically Informed Associations Linking Psychiatric and Immune-Related Phenotypes

et al. 2022

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IMPORTANCE Certain psychiatric and immune-related disorders are reciprocal risk factors. However, the nature of these associations is unclear.OBJECTIVE To characterize the pleiotropy between psychiatric and immune-related traits, as well as risk factors of hypothesized relevance. DESIGN, SETTING, AND PARTICIPANTSThis genetic association study was conducted from July 10, 2020, to January 15, 2022. Analyses used genome-wide association (GWA) statistics related to 14 psychiatric traits; 13 immune-related phenotypes, ie, allergic, autoimmune, and inflammatory disorders; and 15 risk factors related to health-related behaviors, social determinants of health, and stress response. Genetically correlated psychiatric-immune pairs were assessed using 2-sample mendelian randomization (MR) with sensitivity analyses and multivariable adjustment for genetic associations of third variables. False discovery rate correction (Q value < .05) was applied for each analysis. EXPOSURES Genetic associations.MAIN OUTCOMES AND MEASURES Genetic correlations and MR association estimates with SEs and P values. A data-driven approach was used that did not test a priori planned hypotheses. RESULTSA total of 44 genetically correlated psychiatric-immune pairs were identified, including 31 positive correlations (most consistently involving asthma, Crohn disease, hypothyroidism, and ulcerative colitis) and 13 negative correlations (most consistently involving allergic rhinitis and type 1 diabetes). Correlations with third variables were especially strong for psychiatric phenotypes. MR identified 7 associations of psychiatric phenotypes on immune-related phenotypes that were robust to multivariable adjustment, including the positive association of (1) the psychiatric cross-disorder phenotype with asthma (odds ratio [OR], 1.04; 95% CI, 1.02-1.06), Crohn disease (OR, 1.09; 95% CI, 1.05-1.14), and ulcerative colitis (OR, 1.09; 95% CI, 1.05-1.14); (2) major depression with asthma (OR, 1.25; 95% CI, 1.13-1.37); (3) schizophrenia with Crohn disease (OR, 1.12; 95% CI, 1.05-1.18) and ulcerative colitis (OR, 1.14; 95% CI, 1.07-1.21); and a negative association of risk tolerance with allergic rhinitis (OR, 0.77; 95% CI, 0.67-0.92). CONCLUSIONS AND RELEVANCEResults of this genetic association study suggest that genetic liability for psychiatric disorders was associated with liability for several immune disorders, suggesting that vertical pleiotropy related to behavioral traits (or correlated third variables) contributes to clinical associations observed in population-scale data.

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Section: Introductionmentioning

confidence: 99%

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An Atlas of Genetic Correlations and Genetically Informed Associations Linking Psychiatric and Immune-Related Phenotypes

et al. 2022

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“…A number of environmental factors associated with MS development have been discovered through large case-control and cohort studies, including infectious mononucleosis, obesity during adolescence, cigarette smoking, and low serum vitamin D 2 . A protective link between alcohol consumption and MS risk has been demonstrated in Swedish 3,4 and Danish 5 cohorts, but evidence from other cohorts 6 and mendelian randomisation studies 7,8 have failed to support this relationship.…”

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confidence: 99%

No evidence for an association between alcohol consumption and Multiple Sclerosis risk: a UK Biobank study

Dreyer-Alster

Achiron

Giovannoni

et al. 2022

Sci Rep

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Multiple Sclerosis (MS) has been linked to a variety of environmental risk factors, including smoking, Epstein-Barr Virus infection, and childhood obesity. There is some evidence to support a relationship between alcohol consumption and MS risk, but this finding has been inconsistent across cohorts. A protective link between alcohol consumption and MS risk is seen in Swedish and Danish cohorts, however evidence from other cohorts and mendelian randomisation studies have failed to support this relationship. We assessed the relationship between alcohol consumption (never vs. ever drinking) and MS in 409,228 individuals (2100 with MS) from UK Biobank (UKB). We used multivariable logistic regression models adjusted for age and sex. To determine whether there was evidence of statistical interaction between alcohol consumption and HLA-DRB1*15:01 genotype, we calculated interaction on the additive and multiplicative scales. We analysed data from 2100 individuals with MS (72.3% female, median age at recruitment 56) and 407,128 controls (53.9% female, median age at recruitment 58). We found no evidence for an association between alcohol consumption and MS risk (OR = 1.12, 95% CI 0.61–2.08, p = 0.314). As expected, the HLA-DRB1*15:01 allele was strongly associated with MS risk (OR = 2.72, 95% CI 2.72–2.72, p < 2 × 10−16). We found no evidence of statistical interaction between non-drinking and MS risk on either the multiplicative scale (p = 0.8) or on the additive scale (Attributable Proportion = 0.03, 95% CI − 0.43–0.29, P = 0.45). Empirical power calculations indicated reasonable statistical power (85%) to detect a protective effect of alcohol consumption of Relative Risk ≤ 0.7. We were thus unable to replicate findings from other cohorts within UK Biobank. The inconsistent association seen between studies may reflect limited statistical power to detect a weak effect, differences in population characteristics, or the lack of a true causal association.

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“…Several studies have demonstrated that alcohol modulates the immune system in a dose- and time-dependent manner ( 40 , 41 ). However, in a recent Mendelian randomization analysis conducted by Xia Jiang et al., alcohol intake did not show a causal role in IBD risk ( 42 ). In addition, our study did not find any association between alcohol intake and IBD either.…”

Section: Discussionmentioning

confidence: 99%

Mendelian randomization analysis reveals causal effects of food intakes on inflammatory bowel disease risk

2022

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Traditional observational studies have indicated a link between specific food intakes and inflammatory bowel disease (IBD), but the nature of such links remains unknown. We sought to assess the potential causal relationship between food intakes and IBD risk using Mendelian randomization methods. This study used summary statistics data from large-scale genome-wide association studies (GWAS) on food intakes, Crohn’s disease (CD), and ulcerative colitis (UC). In the primary analysis, we used the inverse variance-weighted method to determine whether specific food was causal for CD and UC. In addition, we also ran four other Mendelian randomization methods, including MR Egger, weighted median, maximum likelihood, and weighted mode as a complement. The primary analysis showed that high consumption of poultry (OR, 3.696; 95% CI, 1.056–12.937; p = 0.041) and cereal (OR, 2.449; 95% CI, 1.094–5.482; p = 0.029) had a significant causal association with CD, while high oily fish intake level was found to be statistically significantly associated with the risk of UC (OR, 1.482; 95% CI, 1.002–2.194; p = 0.049). This MR study provides evidence of a potential causal link between certain food intake and CD and UC.

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Alcohol Consumption and Risk of Common Autoimmune Inflammatory Diseases—Evidence From a Large-Scale Genetic Analysis Totaling 1 Million Individuals

Cited by 17 publications

References 25 publications

An Atlas of Genetic Correlations and Genetically Informed Associations Linking Psychiatric and Immune-Related Phenotypes

An Atlas of Genetic Correlations and Genetically Informed Associations Linking Psychiatric and Immune-Related Phenotypes

No evidence for an association between alcohol consumption and Multiple Sclerosis risk: a UK Biobank study

Mendelian randomization analysis reveals causal effects of food intakes on inflammatory bowel disease risk

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