Associations between attention-deficit/hyperactivity disorder and allergic diseases: a two-sample Mendelian randomization study.
In some observational studies, attention-deficit/hyperactivity disorder has been linked to allergic diseases, but the findings are debatable. This study aimed to determine whether attention-deficit/hyperactivity disorder (ADHD) is causally related to allergic asthma, allergic rhinitis, pollen allergy, allergic urticaria, and allergic conjunctivitis using the two-sample Mendelian Randomization (MR) approach.
We did a two-sample Mendelian randomization (MR) study, which chose single nucleotide polymorphisms (SNPs) that are highly associated with attention-deficit/hyperactivity disorder (ADHD) levels from the Psychiatric Genomics Consortium (PGC) on 20,183 cases and 35,191 controls as our instruments. Outcomes datasets included genome-wide association study (GWAS) meta-analysis (n = 1,415,804). The summary statistics of outcome data were obtained from the FinnGen datasets including allergic asthma (10,877 cases and 180,942 controls), allergic rhinitis (8,430 cases and 298,829 controls), pollen allergy (4555cases and 301,734 controls), allergic urticaria (1792 cases and 299,491 controls) and allergic conjunctivitis (15,567 cases and 293,587 controls). Inverse variance weighted, MR-Egger, weighted median, were used to estimate the causal association between ADHD and allergic diseases. Cochran's Q test was used to quantify the heterogeneity of instrumental variables. MR-Egger intercept test, leave-one-out analysis, and the funnel plot were all used in sensitivity analyses.
The Mendelian randomization (MR) analysis indicated that ADHD in inverse variance weighted [odds ratio (OR) = 1.0612; 95% confidence interval (CI):1.0192-1.1049; p = 0.0039] lightly increased the risk of allergic asthma. In MR sensitivity analyses of the weighted median, a similar association was found. But no evidence for an effect of ADHD on allergic asthma risk was found in additional methods: MR-Egger (OR = 0.9592, 95% CI: 0.8384-1.0974, p = 0.5457), and weighted median (OR: =1.0341, 95% CI: 0.9785-1.0929, p = 0.2330). Also, no strong evidence for an effect of ADHD on other allergic diseases (allergic rhinitis, pollen allergy, allergic urticaria, and allergic conjunctivitis) incidence was found using the inverse variance weighted (IVW) method, weighted median method, and MR-Egger regression.
Although several studies have found a link between ADHD and allergic diseases, our findings do not support that ADHD could increase allergic diseases incidence. Randomized controlled trials or Mendelian randomization studies with larger samples are still needed to draw more precise conclusions.
Zhang X
，Zhang R
，Zhang Y
，Lu T
... -
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A bidirectional Mendelian randomization study about the role of morning plasma cortisol in attention deficit hyperactivity disorder.
Cortisol, a hormone regulated by the hypothalamic-pituitary-adrenal (HPA) axis, has been linked to attention deficit hyperactivity disorder (ADHD). The nature of the relationship between cortisol and ADHD, and whether it is causal or explained by reverse causality, remains a matter of debate.
This study aims to evaluate the bidirectional causal relationship between morning plasma cortisol levels and ADHD.
This study used a bidirectional 2-sample Mendelian randomization (MR) design to analyze the association between morning plasma cortisol levels and ADHD using genetic information from the authoritative Psychiatric Genomics Collaboration (PGC) database (n = 55,347) and the ADHD Working Group of the CORtisol NETwork (CORNET) Consortium (n = 12,597). MR analyses were employed: inverse variance weighting (IVW), MR-Egger regression, and weighted medians. OR values and 95% CI were used to evaluate whether there was a causal association between morning plasma cortisol levels on ADHD and ADHD on morning plasma cortisol levels. The Egger-intercept method was employed to test for level pleiotropy. Sensitivity analysis was performed using the "leave-one-out" method, MR pleiotropy residual sum, and MR pleiotropy residual sum and outlier (MR-PRESSO).
Findings from bidirectional MR demonstrated that lower morning plasma cortisol levels were associated with ADHD (ADHD-cortisol OR = 0.857; 95% CI, 0.755-0.974; P = 0.018), suggesting there is a reverse causal relationship between cortisol and ADHD. However, morning plasma cortisol levels were not found to have a causal effect on the risk of ADHD (OR = 1.006; 95% CI, 0.909-1.113; P = 0.907), despite the lack of genetic evidence. The MR-Egger method revealed intercepts close to zero, indicating that the selected instrumental variables had no horizontal multiplicity. The "leave-one-out" sensitivity analysis revealed stable results, with no instrumental variables significantly affecting the results. Heterogeneity tests were insignificant, and MR-PRESSO did not detect any significant outliers. The selected single-nucleotide polymorphisms (SNPs) F were all >10, indicating no weak instrumental variables. Thus, the overall MR analysis results were reliable.
The study findings suggest a reverse causal relationship between morning plasma cortisol levels and ADHD, with low cortisol levels associated with ADHD. No genetic evidence was found to support a causal relationship between morning plasma cortisol levels and the risk of ADHD. These results suggest that ADHD may lead to a significant reduction in morning plasma cortisol secretion.
Jue H
，Fang-Fang L
，Dan-Fei C
，Nuo C
，Chun-Lu Y
，Ke-Pin Y
，Jian C
，Xiao-Bo X
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Associations between ADHD and risk of six psychiatric disorders: a Mendelian randomization study.
Observational studies and diagnostic criteria have indicated that Attention Deficit Hyperactivity Disorder (ADHD) frequently comorbid with various psychiatric disorders. Therefore, we conducted a Mendelian randomization (MR) study to explore this potential genetic association between ADHD and six psychiatric disorders.
Using a two-sample Mendelian randomization (MR) design, this study systematically screened genetic instrumental variables (IVs) based on the genome-wide association studies (GWAS) of ADHD and six psychiatric disorders, with the inverse variance weighted (IVW) method as the primary approach.
The study revealed a positive and causal association between ADHD and the risk of ASD, with an odds ratio (OR) of 2.328 (95%CI: 1.241-4.368) in the IVW MR analysis. Additionally, ADHD showed a positive causal effect on an increased risk of schizophrenia, with an OR of 1.867 (95%CI: 1.260-2.767) in the IVW MR analysis. However, no causal effect of Tic disorder, Mental retardation, Mood disorders and Anxiety disorder with ADHD was found in the analysis mentioned above.
Our MR analysis provides robust evidence of the causal role of ADHD in increasing the risk of ASD and schizophrenia. However, ADHD is not associated with the risk of Tic Disorder, Mental Retardation, Mood Disorders and Anxiety Disorder. This suggests the need for increased attention to the co-occurrence of ADHD-ASD or ADHD-schizophrenia and the implementation of timely intervention and treatment.
Guo Y
，Li J
，Hu R
，Luo H
，Zhang Z
，Tan J
，Luo Q
... -
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Risk of Parkinson's disease and depression severity in different populations: A two-sample Mendelian randomization analysis.
Depression is widely recognized as a common non-motor symptom of Parkinson's disease (PD). Across different studies, the reported prevalence of depression in PD varies widely, ranging from 2.7% to 90%, but it is unclear whether this association is due to genetic or acquired factors. Whether there is a causal relationship remains unknown. The aim of this study was to use a two-sample Mendelian randomization (MR) approach to investigate the causal effect of PD on depression.
Analyses were conducted separately for individuals of European and East Asian ancestry using publicly available summary data from genome-wide association studies. Depression was divided into two categories: ever depressed for a whole week and major depressive disorder (MDD). PD data were used as the exposure and were obtained from the International Parkinson's Disease Genomics Consortium and the BioBank Japan PheWeb, while depression data were used as the outcome and were obtained from the ntegrative Epidemiology Unit (IEU) Open GWAS Project(A public GWAS database） and the Psychiatric Genomics Consortium. The influence of PD on depression was assessed using inverse variance weighted (IVW), weighted median, MR-Egger, and weighted mode methods. Heterogeneity and pleiotropy were tested, and the results were validated using FinnGen GWAS data from version R9.
In individuals of European ancestry, there was a causal relationship between PD and ever depressed for a whole week (IVW method, odds ratio [OR] = 0.990; 95% CI, 0.984-0.996; p = .002), but no causal relationship was observed between PD and MDD (IVW method, OR = 0.974; 95% CI, 0.942-1.009; p = .141). In individuals of East Asian ancestry, no causal relationship was observed between PD and ever depressed for a whole week (IVW method, OR = 1.001; 95% CI, 0.829-1.209; p = .990) and between PD and MDD (IVW method, OR = 1.017; 95% CI, 0.982-1.052; p = .342). The results of the three additional analysis methods were similar to those of the IVW method, and there was no heterogeneity according to Cochran's Q-test. There was no evidence of pleiotropy based on MR-Egger intercept test and MR-PRESSO. The FinnGen validation dataset supported these findings. The results are stable and reliable.
The observed increase in depression among PD patients could potentially be attributed to modifiable acquired factors. Consequently, there is an urgent need to strengthen the management of PD patients in order to prevent the development of depression in the future.
Qin Y
，Li J
，Quan W
，Song J
，Xu J
，Chen J
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《Brain and Behavior》
ResearchGate
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