Gene mapping and annotation

In order to map the discovered SNPs and genetic loci onto their affiliated genes we used the FUMA toolbox¹. FUMA performs GWAS annotation of lead SNPs within genetic loci in the GWAS summary statistics. FUMA also provides functionality to perform gene-set analysis through MAGMA², which compares the mapped genes to predefined sets of genes associated with a number of biological processes or tissues.

Other toolboxes which focus on gene set analysis include reactome^3,4 and SynGO⁵. Reactome is a pathway analysis tool that compares a users’ gene set to a database with large variety of biological interactions and pathways where these interactions play a role^3,4. SynGO functions in a similar fashion but specializes in processes relevant to the biology of the synapse⁵.

1.

Watanabe K, Taskesen E, van Bochoven A, Posthuma D. Functional mapping and annotation of genetic associations with FUMA. Nature Communications [Internet]. 2017 Nov 28;8(1):1826. Available from: https://doi.org/10.1038/s41467-017-01261-5

2.

de Leeuw CA, Mooij JM, Heskes T, Posthuma D. MAGMA: Generalized Gene-Set Analysis of GWAS Data. PLOS Computational Biology [Internet]. 2015 Apr 17;11(4):e1004219. Available from: https://doi.org/10.1371/journal.pcbi.1004219

3.

Gillespie M, Jassal B, Stephan R, Milacic M, Rothfels K, Senff-Ribeiro A, et al. The reactome pathway knowledgebase 2022. Nucleic Acids Research [Internet]. 2022 Jan 7 [cited 2022 Apr 12];50(D1):D687–92. Available from: https://doi.org/10.1093/nar/gkab1028

4.

Jassal B, Matthews L, Viteri G, Gong C, Lorente P, Fabregat A, et al. The reactome pathway knowledgebase. Nucleic Acids Res. 2020 Jan 8;48(D1):D498–503.

5.

Koopmans F, van Nierop P, Andres-Alonso M, Byrnes A, Cijsouw T, Coba MP, et al. SynGO: An Evidence-Based, Expert-Curated Knowledge Base for the Synapse. Neuron [Internet]. 2019 Jul 17;103(2):217–234.e4. Available from: https://www.sciencedirect.com/science/article/pii/S0896627319304271