Mendelian randomization for Alzheimer's disease

The MRAD(Mendelian randomization for Alzheimer's disease) app was created to identify risk or protective factors for Alzheimer's disease. The Inverse Variance Weighted (IVW) random effects model was used as the primary analytical method to performed mendelian randomization analysis. To assess the robustness of the IVW results, 6 other models were used as sensitivity analyses. Meanwhile, heterogeneity test and egger intercept test were used to assess heterogeneity and horizontal pleiotropy. The app includes 73,129 records based on IVW method, of that 4,840 exposure traits split into 10 categories, with MR results available for multiple Alzheimer's disease outcome GWAS. Click here to see our study design. Click here to see MRAD user guide.
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IVW results for Alzheimer's disease outcomes


Exposures with no effect
Heterogeneity test:
Egger Intercept test:
80 traits with consistent effect
across three main outcome datasets:

IVW results for Alzheimer's disease outcomes


Exposures with no effect
Heterogeneity test:
Egger Intercept test:
80 traits with consistent effect
across three main outcome datasets:

Exposures with no effect
Heterogeneity test:
Egger Intercept test:

Sensitivity analysis results for Alzheimer's disease outcomes


Exposures with no effect
Heterogeneity test:
Egger Intercept test:

MRAD User Guide


Home module
The Home module allows users to search through 400,274 records. Users can enter search terms, such as exposure (e.g., LDL cholesterol) or id.exposure (e.g., ebi-a-GCST000759), in the search box. And then click the for searching, for reseting. Furthermore, in the Home module, users can also access the 10 category results of the IVW model (the major analysis method), by checking the corresponding checkbox on the right-hand side (note: only one checkbox can be checked at a time). For example, checking the 'Disease' checkbox will allow users to jump to the results page containing 17,168 disease records.



The search interface includes 20 control widgets. Among these control widgets:
i. There are eight select boxs, including Classification I, Classification II, Classification III, id.outcome, method, effect_direction, Consortium, and Sex, allowing users to make single or multiple selections to filter the data;
ii. The control widgets also include two text input boxs, id.exposure and exposure, which allow users to search by text input (case-insensitive);
iii. The control widgets Min pval and Max pval allow users to search by numerical input (initial values: Min pval = 0, Max pval = 1);
iv. The Heterogeneity test and MR-Egger intercept test checkboxes provide users with a single-click option to obtain data results that have passed heterogeneity and horizontal pleiotropy tests (p>0.05);
v. The Year range slider helps users to filter data based on the year of publication (range: 2007-2022);
vi. Additionally, we have supplemented relevant basic information on biomarker functions and pathways from the public database Uniprot. Users can search for information using the Uniprot Entry ID and Gene Names input boxs and can click on the Uniprot Entry ID Link in the table to go to the corresponding Uniprot page;
vii. The Download , Reset , and Back buttons respectively provide users with the ability to download the data in a .csv format, reset filter conditions of all control widgets, and return to the Home interface.




Study Design module
The Study Design module provides users with a complete MR study design. Moreover, corresponding checkboxes are provided below to allow users to easily access the corresponding details (note: only one checkbox can be selected at a time).




IVW interactive and IVW static modules
The IVW interactive module contains 21 control widgets, including the same search control widgets as in the Home module (due to the large amount of data, the initial values for Classification I and Classification II are set to 'Medical laboratory science' and 'blood lipids and lipoproteins', respectively; users can reset the conditions as needed).
In addition, the IVW interactive module includes the following new features:
i. A checkbox for 'Exposures with no effect', which, when selected (checked by default), allows users to simultaneously remove all exposure traits that do not have significant association (p>0.05) with any of the 16 outcome traits;
ii. A checkbox for '80 traits with consistent effect across three main outcome datasets', which, when selected (unchecked by default), provides users with the option to filter results that have significant and consistent causal association with all the three main outcome traits of AD (p<0.05);
iii. Download Data and Download Interactive buttons provide users with the ability to download data in a .csv format and images in a .html format, respectively.




The IVW interactive module also provides users with interactive visual results. Clicking on the dots on the image will display detailed information on the corresponding id.exposure, exposure, id.outcome, outcome, beta, OR_CI, pval, log10(pval), nsnp, method, Heterogeneity test, and MR-Egger intercept test.




The IVW static module is the same as the IVW interactive module in terms of all the control widgets except for the absence of the Download Interactive button, and contains only static graph results.


Sensitivity analysis interactive and Sensitivity analysis static modules
The Sensitivity analysis interactive module contains 21 control widgets, all of which are the same as those in the IVW interactive module, except that the '80 traits with consistent effects across three main outcome datasets' checkbox is absent, and that the id.outcome option is only available for single selection (initial value: ieu-b-2, users can reset the conditions as needed). In addition, a Sensitivity Analysis Passed select box widget has been added, which allows users to select one or more of the six sensitivity analysis models and obtain statistically significant results (p<0.05).




Interactive visual results are also provided to users. By clicking on the squares in the image, detailed information for id.exposure, exposure, id.outcome, outcome, beta, OR_CI, pval, nsnp, and method is displayed.




The Sensitivity Analysis Static module has the same control widgets as the Sensitivity Analysis Interactive module, except that it does not include the Download Interactive button and only contains static image results.


Licence
MRAD grants you a non-exclusive, non-transferable revocable licence to access and use the app for private or non-commercial research purposes only. If you wish to access and use the app for commercial research purposes, please forward your enquiry to zhaoty22@ mails.jlu.edu.cn.

Ownership of MRAD
Subject to the Licence, nothing in these Terms grants you any right to, or in, any intellectual property rights of any nature (whether existing now or in the future and whether registered or unregistered) in the app.

Anti-racism
You agree to not use the data or methods in the app to make claims about racial superiority. You agree to strictly adhere to the American Society of Human Genetics (ASHG) position statement ASHG Denounces Attempts to Link Genetics and Racial Supremacy and the International Genetic Epidemiology Society Statement on Racism and Genetic Epidemiology.

Vulnerable groups
You agree to adhere to the principles articulated in the final two sections articulated by the ASHG position on Advancing Diverse Participation in Research with Special Consideration for Vulnerable Populations, namely, "In the Conduct of Research with Vulnerable Populations, Researchers Must Address Concerns that Participation May Lead to Group Harm" and "The Benefits of Research Participation Are Profound, Yet the Potential Danger that Unethical Application of Genetics Might Stigmatize, Discriminate against, or Persecute Vulnerable Populations Persists."

Disclaimers
We do not guarantee that (a) the app or any MRAD Data will always be available or interrupted; (b) the app or any MRAD Data will be accurate, complete, free from errors or omissions or secure or free from bugs or viruses; or (c) that the result of using the app or any MRAD Data will be accurate, adequate or fit for any particular purpose. Where the app contains links to other sites or resources provided by third parties, these links are provided for your information only and you acknowledge that we have no control over the content of those sites or resources. All warranties, representations, conditions and all other terms of any kind whatsoever implied by statute or common law, to the fullest extent permitted by applicable, law, excluding from these Terms. Any medical or genetic information is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Limitation of liability
You assume sole responsibility for the results obtained from the use of the app and any MRAD Data and for conclusions drawn from such use. MRAD shall have no liability for any damage or other loss whatsoever arising out of or in connection with your use of the app or any MRAD Data. MRAD shall not be liable in any circumstances whether in contract, tort (including for negligence), misrepresentation (whether innocent or negligent), restitution or otherwise for any special, indirect or consequential loss, costs, damages, charges or expenses however arising under these Terms including but not limited to loss of funding or loss of opportunity, goodwill or reputation. Nothing in these Terms excludes or limits any liability which cannot be excluded or limited by applicable law.

Suspension and termination
MRAD may, at its sole discretion, suspend, withdraw, discontinue or change all or any part of the app (in respect of any single user, group of users or all users of the app) without notice and whether or not arising from any breach of these Terms. MRAD will not be liable to you in such circumstances.

Changes to these Terms
MRAD may revise these Terms at any time by amending this page. Please check this page from time to time to take notice of any changes, as they will be legally binding on you.

Dependencies
The MRAD app project is built upon many important open source software projects.
The MR analysis for all pairs of exposures and outcomes were extracted from MRC IEU OpenGWAS .
The MR analysis was performed based on R packages.
The information and links to proteins were from UniProt .

Credits
You agree to cite any use of the MRAD in the form set out in the “About” page. You further agree to observe and comply with any notice requiring you to cite the original source of any MRAD Data in your analyses in the form set out in such notice.

Computer software copyright
2023SR0730294

How to cite MRAD


Contact us
All comments and suggestions are welcome, especially those suggesting new cases of MRAD and possible improvements on the app. We can be reached at
Tianyu Zhao;
Address: Department of Pharmacology, College of Basic Medical Sciences, Jilin University; 126 Xinmin Street, Changchun City, Jilin Province, People’s Republic of China;
Postcode: 130021
E-mail: zhaoty22@ mails.jlu.edu.cn
Tel:+8613756283023
WeChat: 1172721320
If you find any error in data or bug in web service, please kindly report it to us. Effective Date
This policy is effective as of 3/10/2023.

MRAD(Mendelian randomization for Alzheimer's disease)