Alzheimer's disease

Alzheimer’s disease is the most common form of dementia, affecting persons from 4.4% at age 65 to 22% of persons at age 90 and higher [1]. It is a chronic neurodegenerative disease that usually starts slowly and gets worse over time. The disease is characterized by three primary groups of symptoms [2] [3]. The first group of symptoms are cognitive dysfunctions like memory loss or language difficulties. The second group comprises psychiatric symptoms and behavioral disturbances like depression or hallucinations. The last group of symptoms are difficulties with performing activities of daily life like driving, shopping, getting dressed or even eating unaided. The symptoms of Alzheimers disease progress from mild symptoms of memory loss to very severe dementia [3].


In this use case we analyze SNP data we obtained from a meta-analysis of Alzheimer’s disease [4]. In this study the authors combined data of 4569 individuals (2540 cases and 2029 control) to improve the understanding of genetic risk factors for this disease. From this study we used a list of 66204 SNPs that were identified in all examined individuals. This contained SNPs were ranked by their association with the disease. Then we selected the top 1000 SNPs from this list and performed an ORA enrichment using the entire list as a reference set.

Technical Background

In this use case we want to analyze a unordered set of SNPs, i.e. the top 1000 SNPs in this study. As we have no information about the extend of regulation for each SNP, an Over-Representation Analysis (ORA) has to be performed. This approach is based on the hypergeometric distribution and can be used to test if our set of proteins is significantly more or less present in a biological category than expected by chance.


  • Test set: Unordered set of most important SNPs
  • Reference set: All SNPs analyzed in the study
  • Algorithm: Over-representation analysis (ORA)
  • P-value adjustment method: Benjamini-Hochberg

Step-by-step slideshow

The following slideshow depicts the different analysis steps of the GeneTrail2 workflow (expert mode).


Since our computation is based on SNPs that are often found in patients Alzheimer's disease we expect to find categories that have strong connection to this disease.

Direct associations Alzheimer's disease

By analyzing the enrichment results we see that the top hits are categories that contain SNPs that are directly associated with the disease or that are confirmed to be biomarkers.

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Primary phenotypes

Additionally, we identify primary phenotypes that are described for Alzheimer’s disease like Dementias [1] or Schizophrenia and other psychotic disorders [5].

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Symptoms reported by patients with Alzheimer's disease

Finally, we also find symptoms that are reported in patients with Alzheimer’s disease. Several studies show that patients with this disease have problems with the detection and identification of certain smells and tastes [5] [6]. It has also been reported that patients with Alzheimer’s disease suffer from insomnia.

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  1. Lobo, A and Launer, LJ and Fratiglioni, L and Andersen, K and Di Carlo, A and Breteler, MM and Copeland, JR and Dartigues, JF and Jagger, C and Martinez-Lage, J and others Prevalence of dementia and major subtypes in Europe: A collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology
  2. Burns, Dres Alistair and Iliffe, Steve Enfermedad de Alzheimer BMJ
  3. Burns, Alistair and Jacoby, Robin and Levy, Raymond Psychiatric phenomena in Alzheimer's disease. IV: Disorders of behaviour. The British Journal of Psychiatry RCP
  4. Perez-Palma, Eduardo and Bustos, Bernabe I and Villaman, Camilo F and Alarcon, Marcelo A and Avila, Miguel E and Ugarte, Giorgia D and Reyes, Ariel E and Opazo, Carlos and De Ferrari, Giancarlo V Overrepresentation of glutamate signaling in Alzheimer’s disease: network-based pathway enrichment using meta-analysis of genome-wide association studies PloS one Public Library of Science
  5. Purohit, Dushyant P and Perl, Daniel P and Haroutunian, Vahram and Powchik, Peter and Davidson, Michael and Davis, Kenneth L Alzheimer disease and related neurodegenerative diseases in elderly patients with schizophrenia: a postmortem neuropathologic study of 100 cases Archives of general psychiatry American Medical Association
  6. Doty, Richard L and Reyes, Patricio F and Gregor, Tom Presence of both odor identification and detection deficits in Alzheimer's disease Brain research bulletin Elsevier